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Sample records for human butyrylcholinesterase administered

  1. Butyrylcholinesterase In Human Protein Data,

    Science.gov (United States)

    1992-01-01

    BuChE . CHE. ChE Classifications EC 3.1.1.8. acylcholine acylhydrolase Description Found in human serum or plasma where it is a soluble glycoprotein...developing chicken retina and monkey visual pathway. Physiology!Pathology Clinically important for diagnosis of poisoning by insecticides of the...gene for BCHE in man as well as in monkey, cow. sheep, pig. rabbit, dog. rat. mouse, guinea pig and chicken . The human gene is located on the long arm

  2. 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.

  3. 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

  4. Monoclonal antibodies to human butyrylcholinesterase reactive with butyrylcholinesterase in animal plasma.

    Science.gov (United States)

    Peng, Hong; Brimijoin, Stephen; Hrabovska, Anna; Krejci, Eric; Blake, Thomas A; Johnson, Rudolph C; Masson, Patrick; Lockridge, Oksana

    2016-01-05

    Five mouse anti-human butyrylcholinesterase (BChE) monoclonal antibodies bind tightly to native human BChE with nanomolar dissociation constants. Pairing analysis in the Octet system identified the monoclonal antibodies that bind to overlapping and independent epitopes on human BChE. The nucleotide and amino acid sequences of 4 monoclonal antibodies are deposited in GenBank. Our goal was to determine which of the 5 monoclonal antibodies recognize BChE in the plasma of animals. Binding of monoclonal antibodies 11D8, B2 18-5, B2 12-1, mAb2 and 3E8 to BChE in animal plasma was measured using antibody immobilized on Pansorbin cells and on Dynabeads Protein G. A third method visualized binding by the shift of BChE activity bands on nondenaturing gels stained for BChE activity. Gels were counterstained for carboxylesterase activity. The three methods agreed that B2 18-5 and mAb2 have broad species specificity, but the other monoclonal antibodies interacted only with human BChE, the exception being 3E8, which also bound chicken BChE. B2 18-5 and mAb2 recognized BChE in human, rhesus monkey, horse, cat, and tiger plasma. A weak response was found with rabbit BChE. Monoclonal mAb2, but not B2 18-5, bound pig and bovine BChE. Gels stained for carboxylesterase activity confirmed that plasma from humans, monkey, pig, chicken, and cow does not contain carboxylesterase, but plasma from horse, cat, tiger, rabbit, guinea pig, mouse, and rat has carboxylesterase. Rabbit plasma carboxylesterase hydrolyzes butyrylthiocholine. In conclusion monoclonal antibodies B2 18-5 and mAb2 can be used to immuno extract BChE from the plasma of humans, monkey and other animals. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Bacterial Expression of Human Butyrylcholinesterase as a Tool for Nerve Agent Bioscavengers Development

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    Xavier Brazzolotto

    2017-10-01

    Full Text Available Human butyrylcholinesterase is a performant stoichiometric bioscavenger of organophosphorous nerve agents. It is either isolated from outdated plasma or functionally expressed in eukaryotic systems. Here, we report the production of active human butyrylcholinesterase in a prokaryotic system after optimization of the primary sequence through the Protein Repair One Stop Shop process, a structure- and sequence-based algorithm for soluble bacterial expression of difficult eukaryotic proteins. The mutant enzyme was purified to homogeneity. Its kinetic parameters with substrate are similar to the endogenous human butyrylcholinesterase or recombinants produced in eukaryotic systems. The isolated protein was prone to crystallize and its 2.5-Å X-ray structure revealed an active site gorge region identical to that of previously solved structures. The advantages of this alternate expression system, particularly for the generation of butyrylcholinesterase variants with nerve agent hydrolysis activity, are discussed.

  6. 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

  7. Verification of exposure to organophosphates: Generic mass spectrometric method for detection of human butyrylcholinesterase adducts

    NARCIS (Netherlands)

    Noort, D.; Fidder, A.; Schans, M.J. van der; Hulst, A.G.

    2006-01-01

    We present a generic mass spectrometric method to verify exposure to organophosphates, based on the chemical conversion of the phosphylated peptides obtained after pepsin digestion of human butyrylcholinesterase (HuBuChE) to a common precursor peptide. After exposure of plasma to various

  8. Human butyrylcholinesterase as a general scavenging antidote for nerve agents toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Ashani, Y.; Grunwald, J.; Grauer, E.; Brandeis, R.; Cohen, E.

    1993-05-13

    Butyrylcholinesterase purified from human plasma (HuBChE) was evaluated both in vitro and in vivo as a single prophylactic antidote against multiples of i.v. LD(50) doses of nerve agents (NA) (GA, GB, GD, and VX). Significant therapeutic concentrations of HuBChE were observed in blood even 48 hrs following either i.v. or i.m. injection in mice, rats, guinea pigs, and monkeys. High levels of protection were also demonstrated in a small number of animals exposed to GD vapors. The stoichiometry of the in vivo sequestration of the anti-ChE toxicants was consistent with HuBChE/NA ratio of the molar concentration required to inhibit 100% enzyme activity in vitro. Further, linear correlation was demonstrated between blood level of HuBChE and the extent of protection obtained against the toxicity of NA. It was estimated that in order to obtain reasonable protection, exogenously administered HuBChE should be able to reduce the concentration of the NA to a level below its LD(50) value within less than one blood circulation time. HuBChE significantly prevented GD-induced behavioral deficits. The enzyme itself did not alter performance of cognitive tasks. Thus, HuBChE not only increased survival after NA exposure, but also alleviated post exposure symptoms. without the need for any additional therapeutic drugs (e. g., atropine, pralidoxime chloride, diazepam).

  9. Recombinant human butyrylcholinesterase from milk of transgenic animals to protect against organophosphate poisoning

    OpenAIRE

    Huang, Yue-Jin; Huang, Yue; Baldassarre, Hernan; Wang, Bin; Lazaris, Anthoula; Leduc, Martin; Bilodeau, Annie S; Bellemare, Annie; Côté, Mélanie; Herskovits, Peter; Touati, Madjid; Turcotte, Carl; Valeanu, Loredana; Lemée, Nicolas; Wilgus, Harvey

    2007-01-01

    Dangerous organophosphorus (OP) compounds have been used as insecticides in agriculture and in chemical warfare. Because exposure to OP could create a danger for humans in the future, butyrylcholinesterase (BChE) has been developed for prophylaxis to these chemicals. Because it is impractical to obtain sufficient quantities of plasma BChE to treat humans exposed to OP agents, the production of recombinant BChE (rBChE) in milk of transgenic animals was investigated. Transgenic mice and goats w...

  10. Protection against soman or VX poisoning by human butyrylcholinesterase in guinea pigs and cynomolgus monkeys.

    Science.gov (United States)

    Lenz, David E; Maxwell, Donald M; Koplovitz, Irwin; Clark, Connie R; Capacio, Benjamin R; Cerasoli, Douglas M; Federko, James M; Luo, Chunyuan; Saxena, Ashima; Doctor, Bhupendra P; Olson, Carl

    2005-12-15

    Human butyrylcholinesterase (HuBuChE), purified from outdated human plasma, is being evaluated for efficacy against nerve agents in guinea pigs and cynomolgus monkeys. Previous studies in rodents and nonhuman primates demonstrated that pretreatment of animals with enzymes that can scavenge nerve agents could provide significant protection against behavioral and lethal effects of nerve agent intoxication. In preparation for evaluation of efficacy of HuBuChE prior to initiating an investigational new drug (IND) application, the pharmacokinetics of HuBuChE were evaluated in guinea pigs and in cynomolgus monkeys. HuBuChE was injected intramuscularly (i.m.) at two doses, and blood samples were taken to follow the time-course of HuBuChE in blood for up to 168 h after administration. In guinea pigs, the two doses of HuBuChE, 19.9 and 32.5 mg/kg, produced similar times of maximal blood concentration (T(max) of 26.0 and 26.8 h, respectively) and similar elimination half-times (t(1/2) of 64.6 and 75.5 h, respectively). Enzyme levels were still 10-fold over baseline at 72 h. Based on these data, guinea pigs were administered 150 mg/kg of enzyme i.m. and challenged at T(max). Soman or VX doses were approximately 1.5, 2.0 and 2.0 x LD50 administered subcutaneously (s.c.) in sequence at 90-120 min apart. None of the animals displayed signs of organophosphorus (OP) anticholinesterase intoxication at any of the challenge levels, and all survived for the 14-day duration of the experiment. Similar experiments were carried out with cynomolgus monkeys to determine the pharmacokinetics of HuBuChE and its efficacy against soman. The complete survival of nearly all animals tested to date, coupled with the maximal blood concentration and half-life elimination profile obtained for HuBuChE after i.m. injection, provides strong support for the continued development of HuBuChE as a product to protect against nerve agents.

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

    Science.gov (United States)

    Jun, Daniel; Musilova, Lucie; Musilek, Kamil; Kuca, Kamil

    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” 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. PMID:21673941

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Recombinant human butyrylcholinesterase from milk of transgenic animals to protect against organophosphate poisoning.

    Science.gov (United States)

    Huang, Yue-Jin; Huang, Yue; Baldassarre, Hernan; Wang, Bin; Lazaris, Anthoula; Leduc, Martin; Bilodeau, Annie S; Bellemare, Annie; Côté, Mélanie; Herskovits, Peter; Touati, Madjid; Turcotte, Carl; Valeanu, Loredana; Lemée, Nicolas; Wilgus, Harvey; Bégin, Isabelle; Bhatia, Bhim; Rao, Khalid; Neveu, Nathalie; Brochu, Eric; Pierson, Janice; Hockley, Duncan K; Cerasoli, Douglas M; Lenz, David E; Karatzas, Costas N; Langermann, Solomon

    2007-08-21

    Dangerous organophosphorus (OP) compounds have been used as insecticides in agriculture and in chemical warfare. Because exposure to OP could create a danger for humans in the future, butyrylcholinesterase (BChE) has been developed for prophylaxis to these chemicals. Because it is impractical to obtain sufficient quantities of plasma BChE to treat humans exposed to OP agents, the production of recombinant BChE (rBChE) in milk of transgenic animals was investigated. Transgenic mice and goats were generated with human BChE cDNA under control of the goat beta-casein promoter. Milk from transgenic animals contained 0.1-5 g/liter of active rBChE. The plasma half-life of PEGylated, goat-derived, purified rBChE in guinea pigs was 7-fold longer than non-PEGylated dimers. The rBChE from transgenic mice was inhibited by nerve agents at a 1:1 molar ratio. Transgenic goats produced active rBChE in milk sufficient for prophylaxis of humans at risk for exposure to OP agents.

  14. 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.

  15. Reactivation of Human Acetylcholinesterase and Butyrylcholinesterase Inhibited by Leptophos-Oxon with Different Oxime Reactivators in Vitro

    Science.gov (United States)

    Jun, Daniel; Musilova, Lucie; Pohanka, Miroslav; Jung, Young-Sik; Bostik, Pavel; Kuca, Kamil

    2010-01-01

    We have evaluated in vitro the potency of 23 oximes to reactivate human erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE) inhibited by racemic leptophos-oxon (O-[4-bromo-2,5-dichlorophenyl]-O-methyl phenyl-phosphonate), a toxic metabolite of the pesticide leptophos. Compounds were assayed in concentrations of 10 and 100 μM. In case of leptophos-oxon inhibited AChE, the best reactivation potency was achieved with methoxime, trimedoxime, obidoxime and oxime K027. The most potent reactivators of inhibited BChE were K033, obidoxime, K117, bis-3-PA, K075, K074 and K127. The reactivation efficacy of tested oximes was lower in case of leptophos-oxon inhibited BChE. PMID:21152278

  16. Human Serum Butyrylcholinesterase: A Bioscavenger for the Protection of Humans from Organophosphorus Exposure

    Science.gov (United States)

    2009-10-01

    enzymes. All animals exposed to GB vapor for 60 min showed signs of cardiac and neurological toxicity and died following exposure. Animals exposed to GB...min showed signs of cardiac and neurological toxicity and died following exposure. Animals exposed to GB vapor for 10 min also died, but showed signs...examined. The exogenous administration of AChE from fetal bovine serum and BChE from equine and human (Hu) serum, has been successfully used as a safe

  17. Cresyl saligenin phosphate makes multiple adducts on free histidine, but does not form an adduct on histidine 438 of human butyrylcholinesterase

    OpenAIRE

    Liyasova, Mariya S.; Schopfer, Lawrence M.; Lockridge, Oksana

    2012-01-01

    Cresyl saligenin phosphate (CBDP) is a suspected causative agent of “aerotoxic syndrome”, affecting pilots, crew members and passengers. CBDP is produced in vivo from ortho-containing isomers of tricresyl phosphate (TCP), a component of jet engine lubricants and hydraulic fluids. CBDP irreversibly inhibits butyrylcholinesterase (BChE) in human plasma by forming adducts on the active site serine (Ser-198). Inhibited BChE undergoes aging to release saligenin and o-cresol. The active site histid...

  18. Detection of human butyrylcholinesterase-nerve gas adducts by liquid chromatography-mass spectrometric analysis after in gel chymotryptic digestion.

    Science.gov (United States)

    Tsuge, Kouichiro; Seto, Yasuo

    2006-06-21

    To verify the exposure to nerve gas, a method for detecting human butyrylcholinesterase (BuChE)-nerve gas adduct was developed using LC-electrospray mass spectrometry (ESI-MS). Purified human serum BuChE was incubated with sarin, soman or VX, and the adduct was purified by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and digested in gel by treatment with chymotrypsin. The resulting peptide mixture was subjected to LC-ESI-MS. From the chymotryptic digest of untreated human BuChE, one peak corresponding to the peptide fragment containing the active center serine residue was detected on the extracted ion chromatogram at m/z 948.5, and the sequence was ascertained to be "GESAGAASVSL" by MS/MS analysis. From the chymotryptic digest of the human BuChE-sarin adduct, a singly charged peptide peak was detected on the extracted ion chromatogram at m/z 1,069.5, and the sequence was ascertained to be "GEXAGAASVSL" by MS/MS analysis (X denotes isopropylmethylphosphonylated serine). The difference in molecular weight (120.0 Da) between the active center peptide fragments corresponding to the untreated BuChE and BuChE-sarin adduct was assumed to be derived from the addition of an isopropyl methylphosphonyl moiety to the serine residue. The formation of human BuChE adducts with soman, VX and an aged soman adduct was confirmed by detecting the respective active center peptide fragments using LC-ESI-MS. To apply the established method to an actual biological sample, human serum was incubated with VX, and the adduct was purified by procainamide affinity chromatography followed by SDS-PAGE. After chymotryptic in gel digestion, the ethylphosphonylated active center peptide fragment could be detected, and the structure of the residue was ascertained by LC-ESI-MS analysis.

  19. Comparison of 5 monoclonal antibodies for immunopurification of human butyrylcholinesterase on Dynabeads: KD values, binding pairs, and amino acid sequences.

    Science.gov (United States)

    Peng, Hong; Brimijoin, Stephen; Hrabovska, Anna; Targosova, Katarina; Krejci, Eric; Blake, Thomas A; Johnson, Rudolph C; Masson, Patrick; Lockridge, Oksana

    2015-10-05

    Human butyrylcholinesterase (HuBChE) is a stoichiometric bioscavenger of nerve agents and organophosphorus pesticides. Mass spectrometry methods detect stable nerve agent adducts on the active site serine of HuBChE. The first step in sample preparation is immunopurification of HuBChE from plasma. Our goal was to identify monoclonal antibodies that could be used to immunopurify HuBChE on Dynabeads Protein G. Mouse anti-HuBChE monoclonal antibodies were obtained in the form of ascites fluid, dead hybridoma cells stored frozen at -80 °C for 30 years, or recently frozen hybridoma cells. RNA from 4 hybridoma cell lines was amplified by PCR for determination of their nucleotide and amino acid sequences. Full-length light and heavy chains were expressed, and the antibodies purified from culture medium. A fifth monoclonal was purchased. The 5 monoclonal antibodies were compared for ability to capture HuBChE from human plasma on Dynabeads Protein G. In addition, they were evaluated for binding affinity by Biacore and ELISA. Epitope mapping by pairing analysis was performed on the Octet Red96 instrument. The 5 monoclonal antibodies, B2 12-1, B2 18-5, 3E8, mAb2, and 11D8, had similar KD values of 10(-9) M for HuBChE. Monoclonal B2 18-5 outperformed the others in the Dynabeads Protein G assay where it captured 97% of the HuBChE in 0.5 ml plasma. Pairing analysis showed that 3E8 and B2 12-1 share the same epitope, 11D8 and B2 18-5 share the same epitope, but mAb2 and B2 12-1 or mAb2 and 3E8 bind to different epitopes on HuBChE. B2 18-5 was selected for establishment of a stable CHO cell line for production of mouse anti-HuBChE monoclonal. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Inhibition of human plasma and serum butyrylcholinesterase (EC 3.1.1.8) by alpha-chaconine and alpha-solanine.

    Science.gov (United States)

    Nigg, H N; Ramos, L E; Graham, E M; Sterling, J; Brown, S; Cornell, J A

    1996-10-01

    The purpose of these experiments was to determine the reversibility of alpha-chaconine and alpha-solanine inhibition of human plasma butyrylcholinesterase (BuChE). For the substrate alpha-naphthylacetate, optimal assay conditions were 0.50 M sodium phosphate buffer and a substrate concentration of 3-5 x 10(-4) M. Dibucaine (1 x 10(-5) M) indicated the usual phenotype for all subjects; alpha-chaconine and alpha-solanine at 2.88 x 10(-6) M inhibited BuChE about 70 and 50%, respectively. One- and 24-hr incubations at 1 x 10(-5) M with alpha-chaconine, alpha-solanine, paraoxon, eserine, and ethanol yielded reversible inhibition with dilution except for paraoxon. Twenty-four-hour dialyses of incubations showed no inhibition except for paraoxon. PAGE enzyme activity gels of 1- and 24-hr incubations also showed no inhibition except for paraoxon. alpha-Chaconine and alpha-solanine are reversible inhibitors of human butyrylcholinesterase. At estimated tissue levels, alpha-chaconine, alpha-solanine, and solanidine inhibited BuChE 10-86%. In assays which combined alpha-chaconine, alpha-solanine, and solanidine, inhibition of BuChE was less than additive. No inhibition of albumin alpha-naphthylacetate esterase (an arylesterase) was noted with any inhibitor. The importance of these data to adverse toxicological effects of potato alkaloids is discussed.

  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. Effects of a cocaine hydrolase engineered from human butyrylcholinesterase on metabolic profile of cocaine in rats.

    Science.gov (United States)

    Chen, Xiabin; Zheng, Xirong; Zhou, Ziyuan; Zhan, Chang-Guo; Zheng, Fang

    2016-11-25

    Accelerating cocaine metabolism through enzymatic hydrolysis at cocaine benzoyl ester is recognized as a promising therapeutic approach for cocaine abuse treatment. Our more recently designed A199S/F227A/S287G/A328W/Y332G mutant of human BChE, denoted as cocaine hydrolase-3 (CocH3), has a considerably improved catalytic efficiency against cocaine and has been proven active in blocking cocaine-induced toxicity and physiological effects. In the present study, we have further characterized the effects of CocH3 on the detailed metabolic profile of cocaine in rats administrated intravenously (IV) with 5 mg/kg cocaine, demonstrating that IV administration of 0.15 mg/kg CocH3 dramatically changed the metabolic profile of cocaine. Without CocH3 administration, the dominant cocaine-metabolizing pathway in rats was cocaine methyl ester hydrolysis to benzoylecgonine (BZE). With the CocH3 administration, the dominant cocaine-metabolizing pathway in rats became cocaine benzoyl ester hydrolysis to ecgonine methyl ester (EME), and the other two metabolic pathways (i.e. cocaine methyl ester hydrolysis to BZE and cocaine oxidation to norcocaine) became insignificant. The CocH3-catalyzed cocaine benzoyl ester hydrolysis to EME was so efficient such that the measured maximum blood cocaine concentration (∼38 ng/ml) was significantly lower than the threshold blood cocaine concentration (∼72 ng/ml) required to produce any measurable physiological effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Cresyl saligenin phosphate makes multiple adducts on free histidine, but does not form an adduct on histidine 438 of human butyrylcholinesterase.

    Science.gov (United States)

    Liyasova, Mariya S; Schopfer, Lawrence M; Lockridge, Oksana

    2013-03-25

    Cresyl saligenin phosphate (CBDP) is a suspected causative agent of "aerotoxic syndrome", affecting pilots, crew members and passengers. CBDP is produced in vivo from ortho-containing isomers of tricresyl phosphate (TCP), a component of jet engine lubricants and hydraulic fluids. CBDP irreversibly inhibits butyrylcholinesterase (BChE) in human plasma by forming adducts on the active site serine (Ser-198). Inhibited BChE undergoes aging to release saligenin and o-cresol. The active site histidine (His-438) was hypothesized to abstract o-hydroxybenzyl moiety from the initial adduct on Ser-198. Our goal was to test this hypothesis. Mass spectral analysis of CBDP-inhibited BChE digested with Glu-C showed an o-hydroxybenzyl adduct (+106 amu) on lysine 499, a residue far from the active site, but not on His-438. Nevertheless, the nitrogen of the imidazole ring of free L-histidine formed a variety of adducts upon reaction with CBDP, including the o-hydroxybenzyl adduct, suggesting that histidine-CBDP adducts may form on other proteins. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. 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.

  5. 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.

  6. Conversion of acetylcholinesterase to butyrylcholinesterase: modeling and mutagenesis.

    OpenAIRE

    Harel, M.; Sussman, J.L.; Krejci, E; Bon, S; Chanal, P; Massoulié, J; Silman, I.

    1992-01-01

    Torpedo acetylcholinesterase (AcChoEase, EC 3.1.1.7) and human butyrylcholinesterase (BtChoEase, EC 3.1.1.8), while clearly differing in substrate specificity and sensitivity to inhibitors, possess 53% sequence homology; this permitted modeling human BtChoEase on the basis of the three-dimensional structure of Torpedo AcChoEase. The modeled BtChoEase structure closely resembled that of AcChoEase in overall features. However, six conserved aromatic residues that line the active-site gorge, whi...

  7. Trp82 and Tyr332 are involved in two quaternary ammonium binding domains of human butyrylcholinesterase as revealed by photoaffinity labeling with [3H]DDF.

    Science.gov (United States)

    Nachon, F; Ehret-Sabatier, L; Loew, D; Colas, C; van Dorsselaer, A; Goeldner, M

    1998-07-21

    Purified butyrylcholinesterase (BuChE) was photolabeled by [3H]-p-N, N-dimethylamino benzene diazonium ([3H]DDF) to identify the quaternary ammonium binding sites on this protein [Ehret-Sabatier, L. , Schalk, I., Goeldner, M., and Hirth, C. (1992) Eur. J. Biochem. 203, 475-481]. The covalent photoincorporation occurs with a stoichiometry of one mole of probe per mole of inactivated site and could be fully prevented by several cholinergic inhibitors such as tacrine or tetramethylammonium. After complete deglycosylation of the enzyme using N-glycosidase F, the alkylated protein was trypsinolyzed and the digests were analyzed by HPLC coupled to ES-MS. A direct comparison of tryptic fragments from labeled and unlabeled BuChE allowed us to identify the tryptic peptide Tyr61-Lys103 as carrying the probe. Purification of the labeled peptides by anion-exchange chromatography gave a major radioactive peak which was further fractionated by reversed-phase HPLC leading to three, well-resolved, radioactive peaks. Microsequencing revealed that two of these peaks contained an overlapping sequence starting at Tyr61, while the third peak contained a sequence extending from Thr315. Radioactive signals could be unambiguously attributed to positions corresponding to residues Trp82 and Tyr332. This labeling study establishes the existence of two different binding domains for quaternary ammonium in BuChE and exemplifies additional cation/pi interactions in cholinergic proteins. This work strongly supports the existence of a peripheral anionic site in BuChE, implying residue Tyr332 as a key element.

  8. THE HORSE SERUM BUTYRYLCHOLINESTERASE ACTIVITY UNDER OCTANOL INFLUENCE

    OpenAIRE

    L. P. Kuznetsova; E. R. Nikitina; E. E. Sochilina

    2013-01-01

    Butyrylcholinesterase preparations from horse blood serum widely use in the research purposes and as an analytical reagent for determination of biologically active substances. High sensitivity of butyrylcholinesterase to organophosphorous inhibitors which possess high toxicity for the warm-blooded is especially important. Influence of octanol on reactive capacity of horse serum butyrylcholinesterase to butyrylcholine and ?-naphtylacetate and on its sensitivity to diisopropylfluorophosphat...

  9. 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.

  10. 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.

  11. Inhibitors of Acetylcholinesterase and Butyrylcholinesterase Meet Immunity

    Directory of Open Access Journals (Sweden)

    Miroslav Pohanka

    2014-06-01

    Full Text Available Acetylcholinesterase (AChE inhibitors are widely used for the symptomatic treatment of Alzheimer’s disease and other dementias. More recent use is for myasthenia gravis. Many of these inhibitors interact with the second known cholinesterase, butyrylcholinesterase (BChE. Further, evidence shows that acetylcholine plays a role in suppression of cytokine release through a “cholinergic anti-inflammatory pathway” which raises questions about the role of these inhibitors in the immune system. This review covers research and discussion of the role of the inhibitors in modulating the immune response using as examples the commonly available drugs, donepezil, galantamine, huperzine, neostigmine and pyridostigmine. Major attention is given to the cholinergic anti-inflammatory pathway, a well-described link between the central nervous system and terminal effector cells in the immune system.

  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. Quantification of nerve agent VX-butyrylcholinesterase adduct biomarker from an accidental exposure.

    Science.gov (United States)

    Solano, Maria I; Thomas, Jerry D; Taylor, James T; McGuire, Jeffrey M; Jakubowski, Edward M; Thomson, Sandra A; Maggio, Vincent L; Holland, Kerry E; Smith, J Richard; Capacio, Benedict; Woolfitt, Adrian R; Ashley, David L; Barr, John R

    2008-01-01

    The lack of data in the open literature on human exposure to the nerve agent O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) gives a special relevance to the data presented in this study in which we report the quantification of VX-butyrylcholinesterase adduct from a relatively low-level accidental human exposure. The samples were analyzed by gas chromatography-high resolution mass spectrometry using the fluoride ion regeneration method for the quantification of multiple nerve agents including VX. Six human plasma samples from the same individual were collected after the patient had been treated once with oxime immediately after exhibiting signs of exposure. Detection limits of approximately 5.5 pg/mL plasma were achieved for the G-analogue of VX (G-VX). Levels of the G-VX ranged from 81.4 pg/mL on the first day after the exposure to 6.9 pg/mL in the sample taken 27 days after the exposure. Based on the reported concentration of human butyrylcholinesterase in plasma of approximately 80 nM, it can be calculated that inhibition levels of >or= 0.05% of BuChE can be accurately quantified. These data further indicate that the fluoride ion regeneration method is a potentially powerful tool that can be used to assess low-level exposure to VX.

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

    African Journals Online (AJOL)

    Type 2 diabetes mellitus is a chronic progressive disease typified by a loss of glycaemic control over time as the insulin secreting pancreatic -cells lose their ability to compensate for the prevailing levels of insulin sensitivity. Several abnormalities are associated with diabetes and metabolic syndrome. Butyrylcholinesterase ...

  15. Reversal of succinylcholine induced apnea with an organophosphate scavenging recombinant butyrylcholinesterase

    National Research Council Canada - National Science Library

    Geyer, Brian C; Larrimore, Katherine E; Kilbourne, Jacquelyn; Kannan, Latha; Mor, Tsafrir S

    2013-01-01

    .... In particular, patients who carry genetic or acquired deficiency of butyrylcholinesterase, the serum enzyme responsible for succinylcholine hydrolysis, are susceptible to succinylcholine-induced...

  16. Reversal of Succinylcholine Induced Apnea with an Organophosphate Scavenging Recombinant Butyrylcholinesterase: e59159

    National Research Council Canada - National Science Library

    Brian C Geyer; Katherine E Larrimore; Jacquelyn Kilbourne; Latha Kannan; Tsafrir S Mor

    2013-01-01

    .... In particular, patients who carry genetic or acquired deficiency of butyrylcholinesterase, the serum enzyme responsible for succinylcholine hydrolysis, are susceptible to succinylcholine-induced...

  17. THE HORSE SERUM BUTYRYLCHOLINESTERASE ACTIVITY UNDER OCTANOL INFLUENCE

    Directory of Open Access Journals (Sweden)

    L. P. Kuznetsova

    2013-12-01

    Full Text Available Butyrylcholinesterase preparations from horse blood serum widely use in the research purposes and as an analytical reagent for determination of biologically active substances. High sensitivity of butyrylcholinesterase to organophosphorous inhibitors which possess high toxicity for the warm-blooded is especially important. Influence of octanol on reactive capacity of horse serum butyrylcholinesterase to butyrylcholine and ?-naphtylacetate and on its sensitivity to diisopropylfluorophosphate is investigated. Enzyme activity measured by a method of potentiometric titration in experiments with butyrylcholine and a fluorimetric method in experiments with ?-naphtylacetate allowing to define speed of hydrolysis of small concentration of a substrate. It is shown, that octanol does not influence on the hydrolysis rate of butyrylcholine but activates the enzymatic hydrolysis of ?-naphtylacetate and reduces the sensitivity of enzyme to inhibition by diisopropylfluorophosphate. The received results have the important practical value as octanol apply in some manufactures in the capacity of a defoamer. Our researches have shown that such standard procedures which used by manufacture of enzyme preparations as salting-out and desalting only partially delete octanol impurities. Complete separation of the enzyme from octanol and its sensitivity reduction to diisopropylfluorophosphate was possible by selective sorption of enzyme protein on the ion-exchange resin with the after-elution by a salt solution.

  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. Evolution of acetylcholinesterase and butyrylcholinesterase in the vertebrates: an atypical butyrylcholinesterase from the Medaka Oryzias latipes.

    Directory of Open Access Journals (Sweden)

    Leo Pezzementi

    2011-02-01

    Full Text Available Acetylcholinesterase (AChE and butyrylcholinesterase (BChE are thought to be the result of a gene duplication event early in vertebrate evolution. To learn more about the evolution of these enzymes, we expressed in vitro, characterized, and modeled a recombinant cholinesterase (ChE from a teleost, the medaka Oryzias latipes. In addition to AChE, O. latipes has a ChE that is different from either vertebrate AChE or BChE, which we are classifying as an atypical BChE, and which may resemble a transitional form between the two. Of the fourteen aromatic amino acids in the catalytic gorge of vertebrate AChE, ten are conserved in the atypical BChE of O. latipes; by contrast, only eight are conserved in vertebrate BChE. Notably, the atypical BChE has one phenylalanine in its acyl pocket, while AChE has two and BChE none. These substitutions could account for the intermediate nature of this atypical BChE. Molecular modeling supports this proposal. The atypical BChE hydrolyzes acetylthiocholine (ATCh and propionylthiocholine (PTCh preferentially but butyrylthiocholine (BTCh to a considerable extent, which is different from the substrate specificity of AChE or BChE. The enzyme shows substrate inhibition with the two smaller substrates but not with the larger substrate BTCh. In comparison, AChE exhibits substrate inhibition, while BChE does not, but may instead show substrate activation. The atypical BChE from O. latipes also shows a mixed pattern of inhibition. It is effectively inhibited by physostigmine, typical of all ChEs. However, although the atypical BChE is efficiently inhibited by the BChE-specific inhibitor ethopropazine, it is not by another BChE inhibitor, iso-OMPA, nor by the AChE-specific inhibitor BW284c51. The atypical BChE is found as a glycophosphatidylinositol-anchored (GPI-anchored amphiphilic dimer (G(2 (a, which is unusual for any BChE. We classify the enzyme as an atypical BChE and discuss its implications for the evolution of ACh

  20. Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans.

    Science.gov (United States)

    Manini, Alex F; Yiannoulos, Georgia; Bergamaschi, Mateus M; Hernandez, Stephanie; Olmedo, Ruben; Barnes, Allan J; Winkel, Gary; Sinha, Rajita; Jutras-Aswad, Didier; Huestis, Marilyn A; Hurd, Yasmin L

    2015-01-01

    Cannabidiol (CBD) is hypothesized as a potential treatment for opioid addiction, with safety studies an important first step for medication development. We determined CBD safety and pharmacokinetics when administered concomitantly with a high-potency opioid in healthy subjects. This double-blind, placebo-controlled cross-over study of CBD, coadministered with intravenous fentanyl, was conducted at the Clinical Research Center in Mount Sinai Hospital, a tertiary care medical center in New York City. Participants were healthy volunteers aged 21 to 65 years with prior opioid exposure, regardless of the route. Blood samples were obtained before and after 400 or 800 mg of CBD pretreatment, followed by a single 0.5 (session 1) or 1.0 μg/kg (session 2) of intravenous fentanyl dose. The primary outcome was the Systematic Assessment for Treatment Emergent Events (SAFTEE) to assess safety and adverse effects. CBD peak plasma concentrations, time to reach peak plasma concentrations (tmax), and area under the curve (AUC) were measured. SAFTEE data were similar between groups without respiratory depression or cardiovascular complications during any test session. After low-dose CBD, tmax occurred at 3 and 1.5 hours in sessions 1 and 2, respectively. After high-dose CBD, tmax occurred at 3 and 4 hours in sessions 1 and 2, respectively. There were no significant differences in plasma CBD or cortisol (AUC P = NS) between sessions. Cannabidiol does not exacerbate adverse effects associated with intravenous fentanyl administration. Coadministration of CBD and opioids was safe and well tolerated. These data provide the foundation for future studies examining CBD as a potential treatment for opioid abuse.

  1. 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....

  2. A Pilot Study Evaluating the Safety of Intravenously Administered Human Amnion Epithelial Cells for the Treatment of Hepatic Fibrosis

    Directory of Open Access Journals (Sweden)

    Rebecca Lim

    2017-08-01

    Full Text Available Liver cirrhosis is the 6th leading cause of death in adults aged 15–59 years in high-income countries. For many who progress to cirrhosis, the only prospect for survival is liver transplantation. While there is some indication that mesenchymal stem cells may be useful in reversing established liver fibrosis, there are limitations to their widespread use – namely their rarity, the need for extensive serial passaging and the associated potential for genomic instability and cellular senescence. To this end, we propose the use of allogeneic amnion epithelial cells. This clinical trial will assess the safety of intravenously delivered allogeneic human amnion epithelial cells (hAECs in patients with compensated liver cirrhosis. This will also provide clinical data that will inform phases 2 and 3 clinical trials with the ultimate goal of developing hAECs as a therapeutic option for patients with cirrhosis who are at significant risk of disease progression. We will recruit 12 patients with compensated cirrhosis, based on their hepatic venous pressure gradient, for a dose escalation study. Patients will be closely monitored in the first 24 h post-infusion, then via daily telephone interviews until clinical assessment on day 5. Long term follow up will include standard liver tests, transient elastography and hepatic ultrasound. Ethics approval was obtained from Monash Health for this trial 16052A, “A Pilot Study Evaluating the Safety of Intravenously Administered Human Amnion Epithelial Cells for the Treatment of Liver Fibrosis, A First in Adult Human Study.” The trial will be conducted in accordance to Monash Health Human Ethics guidelines. Outcomes from this study will be disseminated in the form of conference presentations and submission to a peer reviewed journal. This trial has been registered on the Australian and New Zealand Clinical Trials Registry ACTRN12616000437460.

  3. 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.

  4. Dual inhibition of acetylcholinesterase and butyrylcholinesterase enzymes by allicin.

    Science.gov (United States)

    Kumar, Suresh

    2015-01-01

    The brain of mammals contains two major form of cholinesterase enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The dual inhibition of these enzymes is considered as a promising strategy for the treatment of neurological disorder such as Alzheimer's disease (AD), senile dementia, ataxia, and myasthenia gravis. The present study was undertaken to explore the anticholinesterase inhibition property of allicin. An assessment of cholinesterase inhibition was carried out by Ellman's assay. The present study demonstrates allicin, a major ingredient of crushed garlic (Allium sativum L.) inhibited both AChE and BuChE enzymes in a concentration-dependent manner. For allicin, the IC₅₀ concentration was 0.01 mg/mL (61.62 μM) for AChE and 0.05 ± 0.018 mg/mL (308.12 μM) for BuChE enzymes. Allicin shows a potential to ameliorate the decline of cognitive function and memory loss associated with AD by inhibiting cholinesterase enzymes and upregulate the levels of acetylcholine (ACh) in the brain. It can be used as a new lead to target AChE and BuChE to upregulate the level of ACh which will be useful in alleviating the symptoms associated with AD.

  5. Butyrylcholinesterase gene transfer in obese mice prevents postdieting body weight rebound by suppressing ghrelin signaling

    Science.gov (United States)

    Chen, Vicky Ping; Gao, Yang; Geng, Liyi; Brimijoin, Stephen

    2017-01-01

    The worldwide prevalence of obesity is increasing at an alarming rate but treatment options remain limited. Despite initial success, weight loss by calorie restriction (CR) often fails because of rebound weight gain. Postdieting hyperphagia along with altered hypothalamic neuro-architecture appears to be one direct cause of this undesirable outcome. In response to calorie deficiency the circulating levels of the appetite-promoting hormone, acyl-ghrelin, rise sharply. We hypothesize that proper modulation of acyl-ghrelin and its receptor’s sensitivity will favorably impact energy intake and reprogram the body weight set point. Here we applied viral gene transfer of the acyl-ghrelin hydrolyzing enzyme, butyrylcholinesterase (BChE), in a mouse model of diet-induced obesity. Our results confirmed that BChE overexpression decreased circulating acyl-ghrelin levels, suppressed CR-provoked ghrelin signaling, and restored central ghrelin sensitivity. In addition to maintaining healthy body weights, BChE treated mice had modest postdieting food intake and showed normal glucose homeostasis. Spontaneous activity and energy expenditure did not differ significantly between treated and untreated mice after body weight rebound, suggesting that BChE gene transfer did not alter energy expenditure in the long term. These findings indicate that combining BChE treatment with CR could be an effective approach in treating human obesity and aiding lifelong weight management. PMID:28973869

  6. High performance liquid chromatographic determination of some co-administered anticancer drugs in pharmaceutical preparations and in spiked human plasma.

    Science.gov (United States)

    Fahmy, Ossama T; Korany, Mohamed A; Maher, Hadir M

    2004-03-10

    Two HPLC methods are introduced in this paper for the simultaneous determination of doxorubicin hydrochloride (DOX) and 5-fluorouracil (5-FU), combination I, and of cytarabine (CYT) and etoposide (ETO), combination II, as co-administered drugs. In both combinations, a [250 mm x 4.6 mm C-18 column is used. The mobile phase for combination I consists of a mixture of acetonitrile and 0.05 M disodium hydrogenphosphate (50:50, v/v) containing 0.1% sodium laurylsulfate (SLS) adjusted to pH 3.7 at a flow rate 1 ml/min, with UV detection at 260 nm and ambient temperature. For combination II, the mobile phase consists of a mixture of 0.02 M sodium dihydrogenphosphate aqueous solution adjusted to pH 6.0 (with 0.2 M orthophosphoric acid or sodium hydroxide) and acetonitrile in a ratio of (7:3) at a flow rate 1 ml/min, with UV detection at 254 nm and ambient temperature. The methods also permitted the determination of methyl hydroxybenzoate (MHB) which is used as a preservative in DOX vials, combination I, and of benzyl alcohol (BZA) preservative in ETO vials, combination II. The proposed HPLC methods were successfully applied to the determination of the investigated drugs, of the two combinations, both in injection solutions and spiked human plasma samples with high precision and accuracy. Linearity, validation, accuracy, precision, limits of detection, limits of quantitation, and other aspects of analytical validation are presented in the text.

  7. Phase I clinical trial of systemically administered TUSC2(FUS1-nanoparticles mediating functional gene transfer in humans.

    Directory of Open Access Journals (Sweden)

    Charles Lu

    Full Text Available Tumor suppressor gene TUSC2/FUS1 (TUSC2 is frequently inactivated early in lung cancer development. TUSC2 mediates apoptosis in cancer cells but not normal cells by upregulation of the intrinsic apoptotic pathway. No drug strategies currently exist targeting loss-of-function genetic abnormalities. We report the first in-human systemic gene therapy clinical trial of tumor suppressor gene TUSC2.Patients with recurrent and/or metastatic lung cancer previously treated with platinum-based chemotherapy were treated with escalating doses of intravenous N-[1-(2,3-dioleoyloxypropyl]-N,N,N-trimethylammonium chloride (DOTAP:cholesterol nanoparticles encapsulating a TUSC2 expression plasmid (DOTAP:chol-TUSC2 every 3 weeks.Thirty-one patients were treated at 6 dose levels (range 0.01 to 0.09 milligrams per kilogram. The MTD was determined to be 0.06 mg/kg. Five patients achieved stable disease (2.6-10.8 months, including 2 minor responses. One patient had a metabolic response on positron emission tomography (PET imaging. RT-PCR analysis detected TUSC2 plasmid expression in 7 of 8 post-treatment tumor specimens but not in pretreatment specimens and peripheral blood lymphocyte controls. Proximity ligation assay, performed on paired biopsies from 3 patients, demonstrated low background TUSC2 protein staining in pretreatment tissues compared with intense (10-25 fold increase TUSC2 protein staining in post-treatment tissues. RT-PCR gene expression profiling analysis of apoptotic pathway genes in two patients with high post-treatment levels of TUSC2 mRNA and protein showed significant post-treatment changes in the intrinsic apoptotic pathway. Twenty-nine genes of the 82 tested in the apoptosis array were identified by Igenuity Pathway Analysis to be significantly altered post-treatment in both patients (Pearson correlation coefficient 0.519; p<0.01.DOTAP:chol-TUSC2 can be safely administered intravenously in lung cancer patients and results in uptake of the gene

  8. Multiple-Dose Pharmacokinetic Behavior of Elvucitabine, a Nucleoside Reverse Transcriptase Inhibitor, Administered over 21 Days with Lopinavir-Ritonavir in Human Immunodeficiency Virus Type 1-Infected Subjects

    NARCIS (Netherlands)

    Colucci, Philippe; Pottage, John C.; Robison, Heather; Turgeon, Jacques; Schuermann, Dirk; Hoepelman, I. M.; Ducharme, Murray P.

    The purpose of this study was to describe the plasma pharmacokinetics (PK) of elvucitabine at different doses when administered daily or every other day for 21 days with lopinavir-ritonavir ( Kaletra) in human immunodeficiency virus (HIV)-infected subjects. Three different dosing regimens of

  9. Evaluation of a Self-Administered Intravaginal Swab for PCR Detection of Genitourinary Tract Infections Including Chlamydia, Gonorrhea, Trichomonas and Human Papillomavirus in Active Duty Military Women

    Science.gov (United States)

    1998-10-01

    Trichomonas bmcei subsp. rhodesiense, K02836; Trypanosoma cmzi, M97956; Toxop/asma gon- gallinae ATCC 30002, Giardia lamblia ATCC SF-741 30888, Chilomastix...Administered Intravaginal Swab for PCR Detection of Genitourinary Tract Infections Including Chlamydia, Gonorrhea, Trichomonas and Human...FUNDING NUMBERS Intravaginal Swab for PCR Detection of Genitourinary DAMD17-96-1-6309 Tract Infections Including Chlamydia, Gonorrhea, Trichomonas

  10. Systemic proliferative changes and clinical signs in cynomolgus monkeys administered a recombinant derivative of human epidermal growth factor.

    Science.gov (United States)

    Reindel, J F; Gough, A W; Pilcher, G D; Bobrowski, W F; Sobocinski, G P; de la Iglesia, F A

    2001-01-01

    Epidermal growth factor (EGF) effects have been explored extensively in vivo in rodents, but little is known about trophic responses in nonhuman primates. A previous publication reports the hyperplastic epithelial/parenchymal changes noted in the digestive tract (tongue, esophagus, stomach, intestine, liver, gallbladder, pancreas, and salivary glands) of adult cynomolgus monkeys treated with recombinant human EGF(1-48) (rhEGF(1-48)). This report documents clinical findings and structural effects in the remaining epithelium-containing tissues of these animals. Two monkeys/sex/dose received rhEGF(1-48) by intravenous bolus at 0 (vehicle), 10, 100, 500 (females only), or 1,000 microg/kg/day (males only) daily for up to 2 weeks. Treatment- and dose-related clinical findings included emesis, fecal alterations (soft feces and diarrhea), lacrimation, nasal discharge, hypoactivity, transient hypotension, and salivation after dosing. Male monkeys administered 1,000 microg/kg became moribund after 5 days of treatment and were necropsied. All other monkeys completed the 2-week treatment period. Necropsy findings in nongastrointestinal tissues were: enlarged, pale kidneys at 100 microg/kg and greater; small thymuses seen sporadically at all doses; and enlarged adrenals and small thyroids in males at 1,000 microqg/kg. Respective organ-to-brain weight ratios at 500 and 1,000 microg/kg for kidneys were 1.5- and 2.6-fold greater and for heart were 1.7- and 1.3-fold greater than controls. Microscopically, pronounced dose-related epithelial hypertrophy and hyperplasia were evident in kidney, urinary bladder, skin (epidermis and adnexa), mammary gland, prostate, seminal vesicles, epididymis, uterus, cervix, vagina, thyroid, thymus, tonsillar crypts, cornea, trachea, and pulmonary airways. Epitheliotrophic effects were conspicuous in many tissues at 100 to 1,000 microg/kg. Changes to renal collecting ducts were present at 10 microg/kg, suggesting that kidneys were a relatively

  11. 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.

  12. Differential impact of glucose administered intravenously and orally on circulating miR-375 levels in human subjects

    DEFF Research Database (Denmark)

    Yan, Xin; Wang, Zhen; Westberg-Rasmussen, Sidse

    2017-01-01

    and blood samples were collected over a 3-hour period. Following a period of at least one week, the same participants were administered an isoglycemic intravenous glucose infusion (IIGI) with the same blood collection protocol. Results: The glucose response curve following the IIGI mimicked that obtained...

  13. Plasma butyrylcholinesterase concentrations in psittacine birds: reference values, factors of variation, and association with feather-damaging behavior.

    Science.gov (United States)

    Grosset, Claire; Bougerol, Christian; Sanchez-Migallon Guzman, David

    2014-03-01

    Butyrylcholinesterase is a glycoprotein enzyme used in the diagnosis of toxicosis by cholinesterase-inhibitor agents like organophosphates and carbamates. In animals, butyrylcholinesterase concentrations have been shown to vary depending on numerous factors such as age, sex, diet, and season of sampling. To establish reference values of plasma butyrylcholinesterase concentrations in common psittacine species, plasma butyrylcholinesterase concentrations were measured in 1942 companion psittacine birds. The birds were classified by age, sex, season, health status, and the presence of feather-damaging behavior. A significant difference was observed among species, with eclectus parrots (Eclectus roratus) having the lowest and African grey parrots (Psittacus erithacus) having the highest reference values. Plasma butyrylcholinesterase concentrations varied by age, health status, and season but not by sex. Concentrations were significantly higher during autumn and spring than during winter and summer, and significantly lower in healthy birds than in sick birds. No significant association between butyrylcholinesterase concentrations and feather-damaging behavior could be established except in lovebirds (Agapornis species). Further research is needed to better understand the effect of nutritional and hormonal factors on butyrylcholinesterase concentrations in psittacine birds and its possible effect on bird cognition.

  14. 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...

  15. Survival and digestibility of orally-administered immunoglobulin preparations containing IgG through the gastrointestinal tract in humans

    National Research Council Canada - National Science Library

    Jasion, Victoria S; Burnett, Bruce P

    2015-01-01

    .... Oral administration of Ig preparations from human serum as well as bovine colostrum and serum have been tested and proven to be safe as well as effective in human clinical trials for a variety...

  16. CATALYTIC DETOXIFICATION OF NERVE AGENT AND PESTICIDE ORGANOPHOSPHATES BY BUTYRYLCHOLINESTERASE ASSISTED WITH NON-PYRIDINIUM OXIMES

    Science.gov (United States)

    Radić, Zoran; Dale, Trevor; Kovarik, Zrinka; Berend, Suzana; Garcia, Edzna; Zhang, Limin; Amitai, Gabriel; Green, Carol; Radić, Božica; Duggan, Brendan M.; Ajami, Dariush; Rebek, Julius; Taylor, Palmer

    2016-01-01

    SYNOPSIS We present here a comprehensive in vitro, ex vivo and in vivo study on hydrolytic detoxification of nerve agent and pesticide organophosphates (OPs) catalyzed by purified human butyrylcholinesterase (hBChE) in combination with novel non-pyridinium oxime reactivators. We identified 2-trimethylammonio-6-hydroxybenzaldehyde oxime (TAB2OH) as an efficient reactivator of OP-hBChE conjugates formed by the nerve agents, VX and cyclosarin, and the pesticide, paraoxon. It was also functional in reactivation of sarin and tabun inhibited hBChE. A three to five-fold enhancement of in vitro reactivation of VX, cyclosarin and paraoxon inhibited hBChE was observed, when compared to the commonly used N-methylpyridinium aldoxime reactivator, 2PAM. Kinetic analysis showed the enhancement resulted from improved molecular recognition of corresponding OP-hBChE conjugates by TAB2OH. The unique features of TAB2OH stem from an exocyclic quaternary nitrogen and a hydroxyl, both ortho to an oxime group on a benzene ring. pH dependences reveal participation of the hydroxyl (pKa=7.6) forming an additional ionizing nucleophile to potentiate the oxime (pKa=10) at physiological pH. The TAB2OH protective indices in therapy of sarin and paraoxon exposed mice were enhanced by 30% – 60% when they were treated with a combination of TAB2OH and sub-stoichiometric hBChE. These results establish that oxime-assisted catalysis is feasible for OP bioscavenging. PMID:23216060

  17. 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.

  18. Phosphobutyrylcholinesterase: phosphorylation of the esteratic site of butyrylcholinesterase by ethephon [(2-chloroethyl)phosphonic acid] dianion.

    Science.gov (United States)

    Haux, J E; Quistad, G B; Casida, J E

    2000-07-01

    Ethephon [(2-chloroethyl)phosphonic acid] has two seemingly unrelated types of biological activity. It is a major agrochemical absorbed by crops, slowly releasing ethylene as a plant growth regulator. Ethephon also inhibits the activity of plasma butyrylcholinesterase (BuChE) in humans, dogs, rats, and mice. This is totally unexpected for an ionized phosphonic acid (mostly the dianion at physiological pH), in contrast to the classical inhibitors (nonionized triester phosphates) which phosphorylate serine at the active site. This study tests the hypothesis that ethephon (as the dianion) also acts as a phosphorylating agent in inhibiting BuChE activity. The sensitivity of plasma BuChE to ethephon (90 min preincubation at 25 degrees C) is greatest for humans, dogs, and mice (IC(50) = 6-23 microM), intermediate for chickens, rabbits, rats, and guinea pigs (IC(50) = 26-53 microM), and lowest for pigs and horses (IC(50) = 92-172 microM). The IC(50) decreases linearly with time on a log-log scale to values of 0.15-0. 3 microM for human, dog, and horse BuChE at 24 h. The inhibition rate is generally related to ethephon concentration, consistent with a bimolecular reaction, e.g., phosphorylation. The extent of inhibition of the esteratic activity of BuChE by ethephon is directly proportional to the extent of inhibition of [(3)H]diisopropyl phosphorofluoridate ([(3)H]DFP) postlabeling which is not reversible on removing the ethephon, either directly or after further incubation for 24 h at 25 degrees C. These observations strongly suggest that ethephon, as DFP, phosphorylates human plasma BuChE at Ser-198 of the esteratic site, or more generally, the formation of a phosphobutyrylcholinesterase. With human plasma BuChE, (2-bromoethyl)- and (2-iodoethyl)phosphonic acids have lower affinities for the site than ethephon but higher phosphorylation rate constants, consistent with their relative hydrolysis rates at pH 7.4 (phosphorylation of water). (2-Chlorohexyl)phosphonic acid is

  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. 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.

  1. 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 (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. 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.

  2. Orally administered Polypodium leucotomos extract decreases psoralen-UVA-induced phototoxicity, pigmentation, and damage of human skin

    NARCIS (Netherlands)

    Middelkamp-Hup, Maritza A.; Pathak, Madhu A.; Parrado, Concepcion; Garcia-Caballero, Tomas; Rius-Díaz, Francisca; Fitzpatrick, Thomas B.; González, Salvador

    2004-01-01

    BACKGROUND: The use of psoralen-UVA (PUVA) in patients of skin phototype I to II is limited by side effects of acute phototoxicity and possible long-term carcinogenesis. OBJECTIVE: We sought to assess oral Polypodium leucotomos (PL) extract in decreasing PUVA-induced phototoxicity of human skin on a

  3. 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).

  4. 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 (CΔ170). 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Petzer, Anél, E-mail: 12264954@nwu.ac.za [Centre of Excellence for Pharmaceutical Sciences, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520 (South Africa); Harvey, Brian H. [Centre of Excellence for Pharmaceutical Sciences, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520 (South Africa); Petzer, Jacobus P. [Division of Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520 (South Africa)

    2014-02-01

    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{sub 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{sub 50}(AChE) = 0.214 μM; IC{sub 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.

  6. 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.

  7. Bioanalytical method for the estimation of co-administered esomeprazole, leflunomide and ibuprofen in human plasma and in pharmaceutical dosage forms using micellar liquid chromatography.

    Science.gov (United States)

    Talaat, Wael

    2017-05-01

    The present study represents a connection between basic science and clinical applied science through providing a bioanalytical method for the analysis of certain co-administered drugs used for the treatment of rheumatoid arthritis. The studied drugs are esomeprazole, leflunomide and ibuprofen. The proposed bioanalytical method is a simple reversed phase high performance liquid chromatographic method using micellar mobile phase. The method is conducted using a Shim-pack VP-ODS (150 mm × 4.6 mm ID) stainless steel column at ambient temperature with ultraviolet detection at 285 nm. The micellar mobile phase consisted of 0.1 m sodium dodecyl sulfate, 10% n-propanol, 0.3% triethylamine in 0.02 m orthophosphoric acid (pH 3.5) and is pumped at a flow rate of 1.0 mL/min. The calibration curve was rectilinear over the concentration range of 0.1-5.0, 0.5-10.0 and 1.0-20.0 μg/mL for esomeprazole, leflunomide and ibuprofen respectively. The proposed method was successfully applied to the analysis of these drugs in dosage forms. The method is extended to the in-vitro, in-vivo determination of these drugs in spiked and real human plasma samples. Copyright © 2016 John Wiley & Sons, Ltd.

  8. 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

  9. Automatable Flow System for Paraoxon Detection with an Embedded Screen-Printed Electrode Tailored with Butyrylcholinesterase and Prussian Blue Nanoparticles

    Directory of Open Access Journals (Sweden)

    Fabiana Arduini

    2015-04-01

    Full Text Available Nowadays extensive volumes of pesticides are employed for agricultural and environmental practices, but they have negative effects on human health. The levels of pesticides are necessarily restricted by international regulatory agencies, thus rapid, cost-effective and in-field analysis of pesticides is an important issue. In the present work, we propose a butyrylcholinesterase (BChE-based biosensor embedded in a flow system for organophosphorus pesticide detection. The BChE was immobilized by cross-linking on a screen-printed electrode modified with Prussian Blue Nanoparticles. The detection of paraoxon (an organophosphorus pesticide was carried out evaluating its inhibitory effect on BChE, and quantifying the enzymatic hydrolysis of butyrylthiocholine before and after the exposure of the biosensor to paraoxon, by measuring the thiocholine product at a working voltage of +200 mV. The operating conditions of the flow system were optimized. A flow rate of 0.25 mL/min was exploited for inhibition steps, while a 0.12 mL/min flow rate was used for substrate measurement. A substrate concentration of 5 mM and an incubation time of 10 min allowed a detection limit of 1 ppb of paraoxon (corresponding to 10% inhibition. The stability of the probe in working conditions was investigated for at least eight measurements, and the storage stability was evaluated up to 60 days at room temperature in dry condition. The analytical system was then challenged in drinking, river and lake water samples. Matrix effect was minimized by using a dilution step (1:4 v/v in flow analysis. This biosensor, embedded in a flow system, showed the possibility to detect paraoxon at ppb level using an automatable and cost-effective bioanalytical system.

  10. The C5 Variant of the Butyrylcholinesterase Tetramer Includes a Noncovalently Bound 60 kDa Lamellipodin Fragment.

    Science.gov (United States)

    Schopfer, Lawrence M; Delacour, Hervé; Masson, Patrick; Leroy, Jacqueline; Krejci, Eric; Lockridge, Oksana

    2017-06-29

    Humans with the C5 genetic variant of butyrylcholinesterase (BChE) have 30-200% higher plasma BChE activity, low body weight, and shorter duration of action of the muscle relaxant succinylcholine. The C5 variant has an extra, slow-moving band of BChE activity on native polyacrylamide gel electrophoresis. This band is about 60 kDa larger than wild-type BChE. Umbilical cord BChE in 100% of newborn babies has a C5-like band. Our goal was to identify the unknown, 60 kDa protein in C5. Both wild-type and C5 BChE are under the genetic control of two independent loci, the BCHE gene on Chr 3q26.1 and the RAPH1 (lamellipodin) gene on Chr 2q33. Wild-type BChE tetramers are assembled around a 3 kDa polyproline peptide from lamellipodin. Western blot of boiled C5 and cord BChE showed a positive response with an antibody to the C-terminus of lamellipodin. The C-terminal exon of lamellipodin is about 60 kDa including an N-terminal polyproline. We propose that the unknown protein in C5 and cord BChE is encoded by the last exon of the RAPH1 gene. In 90% of the population, the 60 kDa fragment is shortened to 3 kDa during maturation to adulthood, leaving only 10% of adults with C5 BChE.

  11. 5,6-Dimethoxybenzofuran-3-one Derivatives: a Novel Series of Dual Acetylcholinesterase/Butyrylcholinesterase Inhibitors Bearing Benzyl Pyridinium Moiety

    Directory of Open Access Journals (Sweden)

    Mohammad Abdollahi

    2013-02-01

    Full Text Available Several studies have been focused on design and synthesis of multi-target anti Alzheimer compounds. Utilizing of the dual Acetylcholinesterase/Butyrylcholinesterase inhibitors has gained more interest to treat the Alzheimer’s disease. As a part of a research program to find a novel drug for treating Alzheimer disease, we have previously reported 6-alkoxybenzofuranone derivatives as potent acetylcholinesterase inhibitors. In continuation of our work, we would like to report the synthesis of 5,6-dimethoxy benzofuranone derivatives bearing a benzyl pyridinium moiety as dual Acetylcholinesterase/Butyrylcholinesterase inhibitors.MethodsThe synthesis of target compounds was carried out using a conventional method. Bayer-Villiger oxidation of 3,4-dimethoxybenzaldehyde furnished 3,4-dimethoxyphenol. The reaction of 3,4-dimethoxyphenol with chloroacetonitrile followed by treatment with HCl solution and then ring closure yielded the 5,6-dimethoxy benzofuranone. Condensation of the later compound with pyridine-4-carboxaldehyde and subsequent reaction with different benzyl halides afforded target compounds. The biological activity was measured using standard Ellman’s method. Docking studies were performed to get better insight into interaction of compounds with receptor.ResultsThe in vitro anti acetylcholinesterase/butyrylcholinesterase activity of compounds revealed that, all of the target compounds have good inhibitory activity against both Acetylcholinesterase/Butyrylcholinesterase enzymes in which compound 5b (IC50 = 52 ± 6.38nM was the most active compound against acetylcholinesterase. The same binding mode and interactions were observed for the reference drug donepezil and compound 5b in docking study.ConclusionsIn this study, we presented a new series of benzofuranone-based derivatives having pyridinium moiety as potent dual acting Acetylcholinesterase/Butyrylcholinesterase inhibitors.

  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. Novel Bisquaternary Oximes—Reactivation of Acetylcholinesterase and Butyrylcholinesterase Inhibited by Paraoxon

    Directory of Open Access Journals (Sweden)

    Daniel Jun

    2009-12-01

    Full Text Available Four novel bisquaternary aldoxime cholinesterase reactivators differing in their chemical structure were prepared. Afterwards, their biological activity was evaluated for their ability to reactivate acetylcholinesterase (AChE; EC 3.1.1.7 and butyrylcholinesterase (BuChE; EC 3.1.1.8 inhibited by paraoxon. Their reactivation activity was compared with standard reactivators—pralidoxime, obidoxime and HI-6—which are clinically used at present. As it resulted, none of the prepared compounds surpassed obidoxime, which is considered to be the most potent compound if used for reactivation of AChE inhibited by paraoxon. In case of BuChE reactivation, two compounds (K053 and K068 achieved similar results as obidoxime.

  14. 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.

  15. 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.

  16. 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.

  17. The quaternary structure of chicken acetylcholinesterase and butyrylcholinesterase; effect of collagenase and trypsin.

    Science.gov (United States)

    Allemand, P; Bon, S; Massoulié, J; Vigny, M

    1981-03-01

    Acetylcholinesterase (EC 3.1.1.7.; AChE) and butyrylcholinesterase (EC 3.1.1.8.; BuChE) from chicken muscle exist as sets of structurally homologous forms with very similar properties. The collagenase sensitivity and aggregation properties of the 'heavy' forms of both enzymes indicate that they possess a collagen-like tail, and their stepwise dissociation by trypsin confirms that they correspond to triple (A12) and double (A8) collagen-tailed tetramers. In addition to this dissociating effect, trypsin digests an important fraction of the catalytic units of AChE, in a progressive manner, removing as much as 30% of the enzyme's mass, without inactivation of the tetramers and of the tailed molecules. The trypsin-modified AChE forms closely resemble the corresponding mammalian AChE forms in their hydrodynamic properties. It is not known whether the trypsin-digestible peptides, which do not appear to be involved in the ionic or hydrophobic interactions of the enzymes, are a fragment of the catalytic subunit or whether they constitute distinct polypeptides.

  18. 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.

  19. HER-2 amplification but not butyrylcholinesterase multability reflects aggressiveness of European-originated ovarian tumors.

    Science.gov (United States)

    Dobianer, K; Hruza, C; Ehrlich, G; Sevelda, P; Czerwenka, K; Soreq, H; Spona, J; Zakut, H

    1995-02-01

    Tumorigenic roles were variably suggested for HER-2 and INT-2 oncogene amplifications and the "atypical" aspartate to glycine mutability in the butyrylcholinesterase (BCHE) gene in ovarian adenocarcinomas. To examine this notion we searched for correlations between these three phenomena and ovarian tumor classification and aggressiveness, using quantitative polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP), and direct PCR sequencing. Our findings revealed no alleles carrying the atypical BCHE mutability in 30 European-originated patients with ovarian tumors compared with 11% (2/18) such alleles in Israeli patients with malignant ovarian tumors. This apparently reflected population diversity rather than disease relationship. INT-2 amplification was observed in 14/94 (15%) of the European patients; however, there was no correlation between this phenomenon and clinicopathological indices in the corresponding patients. In contrast, in 94 tumor samples we found that 40% (38/94) of the cases had HER-2 amplification. Moreover, there was a highly significant correlation (P < 0.008) between the over fivefold HER-2 amplification and ovarian tumor severity. These findings demonstrate an informative value for HER-2 amplification tests in tumor DNA, but not for INT-2 amplification or BCHE mutability, for the assessment of treatment.

  20. 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.

  1. Serum Butyrylcholinesterase Activity: A Biomarker for Parkinson’s Disease and Related Dementia

    Directory of Open Access Journals (Sweden)

    Mei-Xue Dong

    2017-01-01

    Full Text Available Objective. This study aim to determine changes of serum butyrylcholinesterase (BChE activity in PD patients and related dementia. Patients and Methods. Consecutive PD patients and healthy controls were included and clinical data were collected. Fast serum BChE activity was determined and compared between healthy controls and PD patients. Independent risk factors were performed for BChE activity, PD, and related dementia. The relationship between BChE activity and disease severity was also evaluated. Receiver operating characteristic (ROC curves were obtained to explore serum BChE activity in distinguishing PD patients and related dementia. Results. Serum BChE activity mainly independently correlated with gender, albumin, triglyceride, body mass index, and PD. Serum BChE activity decreased in PD patients compared with healthy controls. Based on the ROC curve, the optimal cut-off point was 6864.08 IU/L for distinguishing PD patients, and the sensitivity and specificity values were 61.8% and 72.1%. It inversely correlated with Unified Parkinson’s Disease Rating Scale score. BChE activity decreased in PD-related dementia compared with those without dementia. The sensitivity and specificity values were 70.6% and 76.3%, respectively, with an optimal cut-off point of 6550.00 IU/L. Conclusions. Serum BChE activity can be regarded as a biomarker for PD and related dementia.

  2. 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.

  3. The impact of some natural phenolic compounds on carbonic anhydrase, acetylcholinesterase, butyrylcholinesterase, and α-glycosidase enzymes: An antidiabetic, anticholinergic, and antiepileptic study.

    Science.gov (United States)

    Taslimi, Parham; Caglayan, Cuneyt; Gulcin, İlhami

    2017-12-01

    Natural products from food and plant sources have been used for medicinal usage for ages. Also, natural products with therapeutic significance are compounds derived from animals, plants, or any microorganism. In this study, chrysin, carvacrol, hesperidin, zingerone, and naringin as natural phenols showed excellent inhibitory effects against human (h) carbonic anhydrase (CA) isoforms I and II (hCA I and II), α-glucosidase (α-Gly), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). These phenolic compounds were tested for the inhibition of α-glycosidase, hCA I, hCA II, AChE, and BChE enzymes and demonstrated efficient inhibition profiles with Ki values in the range of 3.70 ± 0.92-79.66 ± 20.81 nM against hCA I, 2.98 ± 0.33-84.88 ± 40.32 nM against hCA II, 4.93 ± 2.01-593.60 ± 134.74 nM against α-Gly, 0.52 ± 0.18-46.80 ± 17.15 nM against AChE, and 1.25 ± 0.22-32.08 ± 2.68 against BChE. © 2017 Wiley Periodicals, Inc.

  4. Inhibition of CD44 gene expression in human skin models, using self-delivery short interfering RNA administered by dissolvable microneedle arrays.

    Science.gov (United States)

    Lara, Maria Fernanda; González-González, Emilio; Speaker, Tycho J; Hickerson, Robyn P; Leake, Devin; Milstone, Leonard M; Contag, Christopher H; Kaspar, Roger L

    2012-08-01

    Treatment of skin disorders with short interfering RNA (siRNA)-based therapeutics requires the development of effective delivery methodologies that reach target cells in affected tissues. Successful delivery of functional siRNA to the epidermis requires (1) crossing the stratum corneum, (2) transfer across the keratinocyte membrane, followed by (3) incorporation into the RNA-induced silencing complex. We have previously demonstrated that treatment with microneedle arrays loaded with self-delivery siRNA (sd-siRNA) can achieve inhibition of reporter gene expression in a transgenic mouse model. Furthermore, treatment of human cultured epidermal equivalents with sd-siRNA resulted in inhibition of target gene expression. Here, we demonstrate inhibition of CD44, a gene that is uniformly expressed throughout the epidermis, by sd-siRNA both in vitro (cultured human epidermal skin equivalents) and in vivo (full-thickness human skin equivalents xenografted on immunocompromised mice). Treatment of human skin equivalents with CD44 sd-siRNA markedly decreased CD44 mRNA levels, which led to a reduction of the target protein as confirmed by immunodetection in epidermal equivalent sections with a CD44-specific antibody. Taken together, these results demonstrate that sd-siRNA, delivered by microneedle arrays, can reduce expression of a targeted endogenous gene in a human skin xenograft model.

  5. Evaluating reptile exposure to cholinesterase-inhibiting agrochemicals by serum butyrylcholinesterase activity.

    Science.gov (United States)

    Sanchez-Hernandez, Juan C

    2003-02-01

    Blood samples from lizards (Gallotia galloti) collected from two agricultural areas (Las Galletas and Punta del Hidalgo) and two reference areas on the Island of Tenerife (Canary Islands, Spain) were analyzed for butyrylcholinesterase (BChE) activity. Serum BChE activity was characterized first by in vitro experiments using selective substrates and inhibitors. Of the total cholinesterase (ChE) activity, 74% could be attributed to BChE activity. This portion of the total ChE activity was inhibited dose dependently by tetraisopropyl pyrophosphoramide and hydrolyzed the substrate butyrylthiocholine iodide. No enzyme inhibition was observed at high substrate concentration. Twenty-one lizards collected from agricultural sampling sites showed significant inhibition (p Galletas and 5.13 +/- 1.48 for lizards from Punta del Hidalgo) compared with BChE activity for lizards from the reference sites (6.35 +/- 1.75 micromol/min/ ml). Las Galletas had the highest number of lizards (22%) with significantly inhibited BChE activity. In vitro assays showed that 10(-4) M pyridine-2-aldoxime methochloride (2-PAM) reactivated dichlorvos- or paraoxon-inhibited BChE activity within a 60-min incubation period. Almost all serum samples with depressed BChE activity that were collected from lizards from agricultural areas responded to 2-PAM reactivation of enzyme activity (8-60% increase in enzyme activity). Reactivation by treatment with 2-PAM confirmed that the depression of BChE activity was attributable to organophosphorus (OP) compounds. Evaluation of BChE activity levels and the chemical reactivation of serum BChE activity in G. galloti using 2-PAM was found to be a sensitive indicator of G. galloti exposure to OP compounds.

  6. Deleterious Effect of Butyrylcholinesterase K-Variant in Donepezil Treatment of Mild Cognitive Impairment.

    Science.gov (United States)

    Sokolow, Sophie; Li, Xiaohui; Chen, Lucia; Taylor, Kent D; Rotter, Jerome I; Rissman, Robert A; Aisen, Paul S; Apostolova, Liana G

    2017-01-01

    Donepezil is an acetylcholinesterase inhibitor frequently prescribed for the treatment of mild cognitive impairment (MCI) though not approved by the Food and Drug Administration for this indication. In Alzheimer's disease, butyrylcholinesterase (BChE) activity increases with disease progression and may replace acetylcholinesterase function. The most frequent polymorphism of BChE is the K-variant, which is associated with lower acetylcholine-hydrolyzing activity. BChE-K polymorphism has been studied in Alzheimer's disease progression and donepezil therapy, and has led to contradictory results. To determine whether BChE-K genotype predicts response to donepezil in MCI. We examined the association between BChE-K genotype and changes in cognitive function using the data collected during the ADCS vitamin E/donepezil clinical trial in MCI. We found significant interactions between BChE-K genotype and the duration of donepezil treatment, with increased changes in MMSE and CDR-SB scores compared to the common allele in MCI subjects treated during the 3-year trial. We found faster MMSE decline and CDR-SB rise in BChE-K homozygous individuals treated with donepezil compared to the untreated. We observed similar interactions between BChE-K genotype and steeper changes in MMSE and CDR-SB scores in APOE4 carriers treated with donepezil compared to controls. BChE-K polymorphisms are associated with deleterious changes in cognitive decline in MCI patients treated with donepezil for 3 years. This indicates that BChE-K genotyping should be performed to help identify subsets of subjects at risk for donepezil therapy, like those carrying APOE4. BChE-K and APOE4 carriers should not be prescribed off-label donepezil therapy for MCI management.

  7. 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.

  8. A comparison of the pharmacodynamic profiles of jet-injected regular human insulin versus conventionally administered insulin aspart in healthy volunteers

    NARCIS (Netherlands)

    Engwerda, E.E.; Tack, C.J.; Galan, B.E. de

    2016-01-01

    AIMS: Rapid-acting insulin analogues are generally preferred over regular human insulin because of their more immediate onset of action and shorter time-action profile. However, these analogues may not always be tolerated by or universally available for people with insulin-requiring diabetes. Jet

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

    Science.gov (United States)

    Loudon, Peter T; Yager, Eric J; Lynch, Debbie T; Narendran, Amithi; Stagnar, Cristy; Franchini, Anthony M; Fuller, James T; White, Phil A; Nyuandi, Julia; Wiley, Clayton A; Murphey-Corb, Michael; Fuller, Deborah H

    2010-06-08

    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.

  10. 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.

  11. 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

    discrimination between direct and indirect effects impossible. Objective: We sought to define the direct, placebo-controlled effects of LPS on insulin resistance and protein and lipid metabolism in the infused human leg without systemic interference from cytokines and stress hormones. Design......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......: This was a randomized, placebo-controlled, single-blinded study. Participants and Intervention: We studied 8 healthy volunteers with bilateral femoral vein and artery catheters during a 3-hour basal and 3-hour hyperinsulinemic-euglycemic clamp period with bilateral muscle biopsies in each period during infusion...

  12. Effect of human umbilical cord blood mesenchymal stem cells administered by intravenous or intravitreal routes on cryo-induced retinal injury.

    Science.gov (United States)

    Mohamed, Eman M; Abdelrahman, Shaimaa A; Hussein, Samia; Shalaby, Sally M; Mosaad, Hala; Awad, Ahmed M B

    2017-03-01

    Traumatic optic neuropathy is an important cause of severe vision loss. So, many attempts were performed to transplant stem cells systemically or locally to regenerate the injured retina. In this study, we investigated the effect of human umbilical cord blood mesenchymal stem cells (hUBMSCs) on histological structure, apoptotic, antiapoptotic, oxidant and antioxidant markers in an experimental model of cryo-induced retinal damage in mice. Forty-eight mice were included with 4 major groups; group I contained 18 mice as controls. The others included 30 mice exposed to cryo-induced retinal injury and were subdivided into three equal groups: group II received no treatment after injury. Group III was intravenously injected with hUCBMSCs after injury and group IV received an intravitreal injection with hUCBMSCs into both eyes. Retinal tissues were used for histopathological, immunological and gene expression studies. Real time-PCR was performed to assess B-cell lymphoma 2 (bcl2), Bcl2-associated X protein (bax), heme oxygenase-1 (hmox-1) and thioredoxin-2 (tnx-2) expression and to assess the differentiation of the stem cells into the retinal tissue. Immunohistochemical analysis was performed to assess caspase-3, 3-nitrotyrosine (3-NT) and basic fibroblast growth factor (bFGF). Disturbed retinal structure was seen in cryo-injured mice while hUCBMSCs treated groups showed nearly normal structure. By real time-PCR, significantly reduced mRNA expressions of Bax and notably enhanced mRNA expression of Bcl-2, hmox-1 and txn-2 were demonstrated in retinal injured mice with hUCBMSCs treatment compared to those without. In addition, immunohistochemical analysis confirmed downregulation of 3-NT and caspase-3 and upregulation of bFGF after hUCBMSCs injection in injured retina. Furthermore, there was no differentiation of transplanted stem cells into the retinal tissue. In conclusions, hUCBMSCs could improve the morphological retinal structure in cryo-induced retinal damage model by

  13. 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....

  14. 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

  15. Rosmarinic acid inhibits some metabolic enzymes including glutathione S-transferase, lactoperoxidase, acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase isoenzymes.

    Science.gov (United States)

    Gülçin, İlhami; Scozzafava, Andrea; Supuran, Claudiu T; Koksal, Zeynep; Turkan, Fikret; Çetinkaya, Songül; Bingöl, Zeynebe; Huyut, Zübeyir; Alwasel, Saleh H

    2016-12-01

    Rosmarinic acid (RA) is a natural polyphenol contained in many aromatic plants with promising biological activities. Carbonic anhydrases (CAs, EC 4.2.1.1) are widespread and intensively studied metalloenzymes present in higher vertebrates. Acetylcholinesterase (AChE, E.C. 3.1.1.7) is intimately associated with the normal neurotransmission by catalysing the hydrolysis of acetylcholine to acetate and choline and acts in combination with butyrylcholinesterase (BChE) to remove acetylcholine from the synaptic cleft. Lactoperoxidase (LPO) is an enzyme involved in fighting pathogenic microorganisms, whereas glutathione S-transferases (GSTs) are dimeric proteins present both in prokaryotic and in eukaryotic organisms and involved in cellular detoxification mechanisms. In the present study, the inhibition effects of rosmarinic acid on tumour-associated carbonic anhydrase IX and XII isoenzymes, AChE, BChE, LPO and GST enzymes were evaluated. Rosmarinic acid inhibited these enzymes with Kis in the range between micromolar to picomolar. The best inhibitory effect of rosmarinic acid was observed against both AChE and BChE.

  16. Complement component C3 and butyrylcholinesterase activity are associated with neurodegeneration and clinical disability in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Shahin Aeinehband

    Full Text Available Dysregulation of the complement system is evident in many CNS diseases but mechanisms regulating complement activation in the CNS remain unclear. In a recent large rat genome-wide expression profiling and linkage analysis we found co-regulation of complement C3 immediately downstream of butyrylcholinesterase (BuChE, an enzyme hydrolyzing acetylcholine (ACh, a classical neurotransmitter with immunoregulatory effects. We here determined levels of neurofilament-light (NFL, a marker for ongoing nerve injury, C3 and activity of the two main ACh hydrolyzing enzymes, acetylcholinesterase (AChE and BuChE, in cerebrospinal fluid (CSF from patients with MS (n = 48 and non-inflammatory controls (n = 18. C3 levels were elevated in MS patients compared to controls and correlated both to disability and NFL. C3 levels were not induced by relapses, but were increased in patients with ≥9 cerebral lesions on magnetic resonance imaging and in patients with progressive disease. BuChE activity did not differ at the group level, but was correlated to both C3 and NFL levels in individual samples. In conclusion, we show that CSF C3 correlates both to a marker for ongoing nerve injury and degree of disease disability. Moreover, our results also suggest a potential link between intrathecal cholinergic activity and complement activation. These results motivate further efforts directed at elucidating the regulation and effector functions of the complement system in MS, and its relation to cholinergic tone.

  17. 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.

  18. Tyrosinase, Acetyl- and Butyryl-Cholinesterase Inhibitory Activity of Stachys lavandulifolia Vahl (Lamiaceae and Its Major Constituents

    Directory of Open Access Journals (Sweden)

    Rosa Tundis

    2015-01-01

    Full Text Available The n-hexane (HE, dichloromethane (DC, methanol (ME, ethanol 70% (ET, and methanol with Soxlhet apparatus (MS extracts of Stachys lavandulifolia aerial parts were screened for their potential tyrosinase, acetylcholinesterase (AChE and butyrylcholinesterase (BChE inhibitory activity. ET and MS inhibited tyrosinase with IC 50 values of 33.4 and 42.8 m g/mL, respectively. The phytochemical investigation of these extracts resulted in the isolation of the known compounds monomelittoside (1, melittoside (2, 5-allosyloxy-aucubin (3, acteoside (4 and arbutin (5. The HE extract, characterized by germacrene D, b -pinene, b -myrcene, and trans-caryophyllene as main constituents, showed the highest AChE inhibitory activity with an IC 50 value of 13.7 m g/mL while DC extract was the most active against BChE (IC 50 value of 143.9 m g/mL. The diterpene stachysolone (6 was isolated from this extract. The antioxidant properties were also investigated by four in vitro methods (DPPH, ABTS, FRAP and b -carotene bleaching tests.

  19. 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.

  20. Local salt substitutes “Obu-otoyo” activate acetylcholinesterase and butyrylcholinesterase and induce lipid peroxidation in rat brain

    Science.gov (United States)

    Oboh, Ganiyu; Ademiluyi, Adedayo O.

    2015-01-01

    Evidence has shown that ingestion of heavy metals can lead to neurodegenerative diseases. This study aimed to investigate the neurotoxic potential of salt substitutes (Obu-Otoyo); salt A (made by burning palm kernel shaft then soaked in water overnight and the extract from the resulting residue is used as the salt substitute) and salt B (an unrefined salt mined from a local site at Ilobu town, Osun-State, Nigeria) by assessing their effect on some key enzymes linked with neurodegenerative disease [acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities] as well as on malondialdehyde (MDA) content of the rat brain. Salt substitutes were fed to normal rats as dietary inclusion at doses of 0.5 and 1.0% for 30 days. Thereafter, the effect of the salt substitutes on AChE and BChE activities as well as on MDA level in the rat brain was determined. The results revealed that the salt substitutes caused a significant (psalt substitutes on AChE and BChE activities could be attributed to the presence of some toxic heavy metals. Therefore, the ability of the salt substitutes to induce lipid peroxidation and activate AChE and BChE activities could provide some possible mechanism for their neurotoxic effect. PMID:27486373

  1. 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

  2. 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.

  3. Comparison of the Inhibition of Monoamine Oxidase and Butyrylcholinesterase Activities by Infusions from Green Tea and Some Citrus Peels

    Directory of Open Access Journals (Sweden)

    Ayokunle O. Ademosun

    2014-01-01

    Full Text Available This study sought to investigate the effect of infusions from green tea (Camellia sinensis and some citrus peels [shaddock (Citrus maxima, grapefruit (Citrus paradisi, and orange (Citrus sinensis] on key enzymes relevant to the management of neurodegenerative conditions [monoamine oxidase (MAO and butyrylcholinesterase (BChE]. The total phenol contents and antioxidant activities as typified by their 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid (ABTS radicals scavenging abilities, ferric reducing antioxidant properties, and Fe2+ chelating abilities were also investigated. Green tea had the highest total phenol (43.3 mg/g and total flavonoid (16.4 mg/g contents, when compared to orange [total phenol (19.6 mg/g, total flavonoid (6.5 mg/g], shaddock [total phenol (16.3 mg/g, total flavonoid (5.2 mg/g], and grapefruit [total phenol (17.7 mg/g, total flavonoid (5.9 mg/g]. Orange (EC50 = 1.78 mg/mL had the highest MAO inhibitory ability, while green tea had the least MAO inhibitory ability (EC50 = 2.56 mg/mL. Similarly, green tea had the least BChE inhibitory ability (EC50 = 5.43 mg/mL when compared to the citrus peels’ infusions. However, green tea infusions had the strongest highest ABTS radical scavenging ability, reducing power, and Fe2+ chelating ability. The inhibition of MAO and BChE activities by the green tea and citrus peels infusions could make them good dietary means for the prevention/management of neurodegenerative conditions.

  4. Butyrylcholinesterase as a marker of inflammation and liver injury in the acute and subclinical phases of canine ehrlichiosis.

    Science.gov (United States)

    do Carmo, Guilherme M; Crivellenti, Leandro Z; Bottari, Nathieli B; Machado, Gustavo; Borin-Crivellenti, Sofia; Moresco, Rafael N; Duarte, Thiago; Duarte, Marta; Tinucci-Costa, Mirela; Morsch, Vera M; Schetinger, Maria Rosa C; Stefani, Lenita M; Da Silva, Aleksandro S

    2015-12-01

    The aim of this study was to evaluate the role of butyrylcholinesterase (BChE) as a marker of inflammation and liver injury in the acute and subclinical phases of canine ehrlichiosis. Forty-two serum samples of dogs naturally infected with Ehrlichia canis were used, of which 24 were from animals with the acute phase of the disease and 18 with subclinical disease. In addition, sera from 17 healthy dogs were used as negative controls. The hematocrit, BChE activity, hepatic injury (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), nitric oxide, and cytokines levels were evaluated. The BChE activity was significantly elevated (P<0.05) in dogs with the acute phase of the disease when compared to healthy animals. However, there was a reduction on BChE activity on dogs with subclinical disease compared to the other two groups. AST and ALT levels were significantly higher (P<0.05) in the acute phase, as well as the inflammatory mediators (NOx, TNF-α, INF-γ, IL-4, IL-6) when compared to the control group. On the other hand, IL-10 levels were lower in the acute phase. Based on these results, we are able to conclude that the acute infection caused by E. canis in dogs leads to an increase on seric BChE activity and some inflammatory mediators. Therefore, this enzyme might be used as a marker of acute inflammatory response in dogs naturally infected by this bacterium. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. 1,500 IU human chorionic gonadotropin administered at oocyte retrieval rescues the luteal phase when gonadotropin-releasing hormone agonist is used for ovulation induction: a prospective, randomized, controlled study

    DEFF Research Database (Denmark)

    Al Humaidan, Peter Samir Heskjær; Ejdrup Bredkjaer, Helle; Westergaard, Lars Grabow

    2010-01-01

    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...

  6. 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

  7. 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),

  8. 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...

  9. Polyionic complexes of butyrylcholinesterase and poly-l-lysine-g-poly(ethylene glycol): Comparative kinetics of catalysis and inhibition and in vitro inactivation by proteases and heat.

    Science.gov (United States)

    Hester, Kirstin; Liu, Jing; Flynn, Nicholas; Sultatos, Lester G; Geng, Liyi; Brimijoin, Stephen; Ramsey, Joshua D; Hartson, Steven; Ranjan, Ashish; Pope, Carey

    2017-09-25

    We previously reported that recombinant human butyrylcholinesterase (rhBChE) complexed with a series of copolymers of poly-l-lysine (PLL) with grafted (polyethylene) glycol (PEG) (i.e., PLL-g-PEG) showed reduced catalytic activity but relatively similar concentration-dependent inactivation of the organophosphorus inhibitor paraoxon. Herein, we compared the kinetics of catalysis (using butyrylthiocholine as the substrate) and inhibition (using four different inhibitors) of free and copolymer-complexed rhBChE. Using scanning electron microscopy, polyionic complexes of rhBChE with three different PLL-g-PEG copolymers (based on PLL size) appeared as spheroid-shaped particles with relatively similar particle sizes (median diameter = 35 nm). Relatively similar particle sizes were also noted using dynamic light scattering (mean = 26-35 nm). The three copolymer-complexed enzymes exhibited reduced kcat (30-33% reduction), but no significant changes in Km. Inhibitory potency (as reflected by the bimolecular rate constant, ki) was similar among the free and copolymer-complexed enzymes when paraoxon was the inhibitor, whereas statistically significant reductions in ki (16-60%) were noted with the other inhibitors. Sensitivity to inactivation by proteases and heat was also compared. Copolymer-complexed enzymes showed lesser time-dependent inactivation by the proteases trypsin and pronase and by heat compared to the free enzyme. Understanding the unique properties of PLL-g-PEG-BChE complexes may lead to enhanced approaches for use of BChE and other protein bioscavengers. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. 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: e101591

    National Research Council Canada - National Science Library

    Emma-Jo Hayton; Annie Rose; Umar Ibrahimsa; Mariarosaria Del Sorbo; Stefania Capone; Alison Crook; Antony P Black; Lucy Dorrell; Tomás Hanke

    2014-01-01

      Trial Design 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...

  11. 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

  12. 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....

  13. 22 CFR 196.4 - Administering office.

    Science.gov (United States)

    2010-04-01

    ... AFFAIRS/GRADUATE FOREIGN AFFAIRS FELLOWSHIP PROGRAM § 196.4 Administering office. The Department of State.... Pickering Foreign Affairs/Graduate Foreign Affairs Fellowship Program and grants to post-secondary... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Administering office. 196.4 Section 196.4...

  14. Tumorigenic effects in Wistar rats orally administered benzo[a] pyrene for two years (gavage studies). Implications for human cancer risks associated with oral exposure to polycyclic aromatic hydrocarbons

    NARCIS (Netherlands)

    Kroese ED; Muller JJA; Mohn GR; Dortant PM; Wester PW; LEO; LPI; CSR

    2002-01-01

    Humans are exposed via the environment and via food to Polycyclic Aromatic Hydrocarbons (PAH), mixtures considered carcinogenic by IARC. A quantitative cancer risk assessment for oral exposure is hampered by the absence of adequate data. The need for experimental data is substantiated by the fact

  15. Noninvasive Imaging of Administered Progenitor Cells

    Energy Technology Data Exchange (ETDEWEB)

    Steven R Bergmann, M.D., Ph.D.

    2012-12-03

    -99% pure population of leukocytes. Viability was assessed using Trypan blue histological analysis. We successfully isolated and labeled ~25-30 x 10{sup 7} CD34+ lymphocytes in cytokine mobilized progenitor cell apharesis harvests. Cells were also subjected to a stat gram stain to look for bacterial contamination, stat endotoxin LAL to look for endotoxin contamination, flow cytometry for evaluation of the purity of the cells and 14-day sterility culture. Colony forming assays confirm the capacity of these cells to proliferate and function ex-vivo with CFU-GM values of 26 colonies/ 1 x 10{sup 4} cells plated and 97% viability in cytokine augmented methylcellulose at 10-14 days in CO{sub 2} incubation. We developed a closed-processing system for the product labeling prior to infusion to maintain autologous cell integrity and sterility. Release criteria for the labeled product were documented for viability, cell count and differential, and measured radiolabel. We were successful in labeling the cells with up to 500 uCi/10{sup 8} cells, with viability of >98%. However, due to delays in getting the protocol approved by the FDA, the cells were not infused in humans in this location (although we did successfully use CD34+ cells in humans in a study in Australia). The approach developed should permit labeling of progenitor cells that can be administered to human subjects for tracking. The labeling approach should be useful for all progenitor cell types, although this would need to be verified since different cell lines may have differential radiosensitivity.

  16. A first-in-human phase 1 trial to evaluate the safety and immunogenicity of the candidate tuberculosis vaccine MVA85A-IMX313, administered to BCG-vaccinated adults.

    Science.gov (United States)

    Minhinnick, Alice; Satti, Iman; Harris, Stephanie; Wilkie, Morven; Sheehan, Sharon; Stockdale, Lisa; Manjaly Thomas, Zita-Rose; Lopez-Ramon, Raquel; Poulton, Ian; Lawrie, Alison; Vermaak, Samantha; Le Vert, Alexandre; Del Campo, Judith; Hill, Fergal; Moss, Paul; McShane, Helen

    2016-03-08

    There is an urgent need for a new and effective tuberculosis vaccine because BCG does not sufficiently prevent pulmonary disease. IMX313 is a novel carrier protein designed to improve cellular and humoral immunity. MVA85A-IMX313 is a novel vaccine candidate designed to boost immunity primed by bacillus Calmette-Guérin (BCG) that has been immunogenic in pre-clinical studies. This is the first evaluation of IMX313 delivered as MVA85A-IMX313 in humans. In this phase 1, open-label first-in-human trial, 30 healthy previously BCG-vaccinated adults were enrolled into three treatment groups and vaccinated with low dose MVA85A-IMX313 (group A), standard dose MVA85A-IMX313 (group B), or MVA85A (group C). Volunteers were followed up for 6 months for safety and immunogenicity assessment. The majority of adverse events were mild and there were no vaccine-related serious AEs. Both MVA85A-IMX313 and MVA85A induced a significant increase in IFN-γ ELISpot responses. There were no significant differences between the Ag85A ELISpot and intracellular cytokine responses between the two study groups B (MVA85A-IMX313) and C (MVA85A) at any time point post-vaccination. MVA85A-IMX313 was well tolerated and immunogenic. There was no significant difference in the number of vaccine-related, local or systemic adverse reactions between MVA85A and MVA85A-IMX313 groups. The mycobacteria-specific cellular immune responses induced by MVA85A-IMX313 were not significantly different to those detected in the MVA85A group. In light of this encouraging safety data, further work to improve the potency of molecular adjuvants like IMX313 is merited. This trial was registered on clinicatrials.gov ref. NCT01879163. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group.

    Science.gov (United States)

    Marty, Michel; Cognetti, Francesco; Maraninchi, Dominique; Snyder, Ray; Mauriac, Louis; Tubiana-Hulin, Michèle; Chan, Stephen; Grimes, David; Antón, Antonio; Lluch, Ana; Kennedy, John; O'Byrne, Kenneth; Conte, PierFranco; Green, Michael; Ward, Carol; Mayne, Karen; Extra, Jean-Marc

    2005-07-01

    This randomized, multicenter trial compared first-line trastuzumab plus docetaxel versus docetaxel alone in patients with human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (MBC). Patients were randomly assigned to six cycles of docetaxel 100 mg/m2 every 3 weeks, with or without trastuzumab 4 mg/kg loading dose followed by 2 mg/kg weekly until disease progression. A total of 186 patients received at least one dose of the study drug. Trastuzumab plus docetaxel was significantly superior to docetaxel alone in terms of overall response rate (61% v 34%; P = .0002), overall survival (median, 31.2 v 22.7 months; P = .0325), time to disease progression (median, 11.7 v 6.1 months; P = .0001), time to treatment failure (median, 9.8 v 5.3 months; P = .0001), and duration of response (median, 11.7 v 5.7 months; P = .009). There was little difference in the number and severity of adverse events between the arms. Grade 3 to 4 neutropenia was seen more commonly with the combination (32%) than with docetaxel alone (22%), and there was a slightly higher incidence of febrile neutropenia in the combination arm (23% v 17%). One patient in the combination arm experienced symptomatic heart failure (1%). Another patient experienced symptomatic heart failure 5 months after discontinuation of trastuzumab because of disease progression, while being treated with an investigational anthracycline for 4 months. Trastuzumab combined with docetaxel is superior to docetaxel alone as first-line treatment of patients with HER2-positive MBC in terms of overall survival, response rate, response duration, time to progression, and time to treatment failure, with little additional toxicity.

  18. A first-in-human phase I dose-escalation, pharmacokinetic, and pharmacodynamic evaluation of intravenous LY2090314, a glycogen synthase kinase 3 inhibitor, administered in combination with pemetrexed and carboplatin.

    Science.gov (United States)

    Gray, Jhanelle E; Infante, Jeffrey R; Brail, Les H; Simon, George R; Cooksey, Jennifer F; Jones, Suzanne F; Farrington, Daphne L; Yeo, Adeline; Jackson, Kimberley A; Chow, Kay H; Zamek-Gliszczynski, Maciej J; Burris, Howard A

    2015-12-01

    LY2090314 (LY) is a glycogen synthase kinase 3 inhibitor with preclinical efficacy in xenograft models when combined with platinum regimens. A first-in-human phase 1 dose-escalation study evaluated the combination of LY with pemetrexed/carboplatin. Forty-one patients with advanced solid tumors received single-dose LY monotherapy lead-in and 37 patients received LY (10-120 mg) plus pemetrexed/carboplatin (500 mg/m(2) and 5-6 AUC, respectively) across 8 dose levels every 21 days. Primary objective was maximum tolerated dose (MTD) determination; secondary endpoints included safety, antitumor activity, pharmacokinetics, and beta-catenin pharmacodynamics. MTD of LY with pemetrexed/carboplatin was 40 mg. Eleven dose-limiting toxicities (DLTs) occurred in ten patients. DLTs during LY monotherapy occurred at ≥ 40 mg: grade 2 visual disturbance (n = 1) and grade 3/4 peri-infusional thoracic pain during or shortly post infusion (n = 4; chest, upper abdominal, and back pain). Ranitidine was added after de-escalation to 80 mg LY to minimize peri-infusional thoracic pain. Following LY with pemetrexed/carboplatin therapy, DLTs included grade 3/4 thrombocytopenia (n = 4) and grade 4 neutropenia (n = 1). Best overall response by RECIST included 5 confirmed partial responses (non-small cell lung cancer [n = 3], mesothelioma, and breast cancer) and 19 patients having stable disease. Systemic LY exposure was approximately linear over dose range studied. Transient upregulation of beta-catenin measured in peripheral blood mononuclear cells (PBMCs) occurred at 40 mg LY. The initial safety profile of LY2090314 was established. MTD LY dose with pemetrexed/carboplatin is 40 mg IV every 3 weeks plus ranitidine. Efficacy of LY plus pemetrexed/carboplatin requires confirmation in randomized trials.

  19. Renal and hepatic histopathology of intraperitoneally administered ...

    African Journals Online (AJOL)

    The biochemistry and histopathology of intraperitoneally administered potassium permanganate was investigated in Clarias gariepinus. Acute toxicity of the ... The potassium permanganate widely used in controlling external fungal, bacterial and protozoan infections of fish should not be indiscriminately used. Keywords: ...

  20. Nurse-administered propofol sedation for endoscopy

    DEFF Research Database (Denmark)

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

    2011-01-01

    for endoscopists and for endoscopy nurses who were administering propofol sedation. The nurses' program comprised a 6-week course including theoretical and practical training in airway management, and the endoscopists' program consisted of 2.5 h of theory and a short course in practical airway management...

  1. Administered Prices and Kinked Demand Curves

    Science.gov (United States)

    Greenaway, David

    1977-01-01

    Identifies some of the more essential features of the administered price thesis and discusses ways they might be integrated into mainstream economic theory. Available from: General Secretary, Economics Association, Room 340, Hamilton House, Mabledon Place, London WC1H 9BH, England. (Author/AV)

  2. Effects of electrical stimulation on molecular forms of butyrylcholinesterase in denervated fast and slow latissimus dorsi muscles of newly hatched chicken.

    Science.gov (United States)

    Khaskiye, A; Sine, J P; Colas, B; Renaud, D

    1990-03-01

    The effects of denervation and direct electrical stimulation upon the activity and the molecular form distribution of butyrylcholinesterase (BuChE) were studied in fast-twitch posterior latissimus dorsi (PLD) and in slow-tonic anterior latissimus dorsi (ALD) muscles of newly hatched chicken. In PLD muscle, denervation performed at day 2 substantially reduced the rate of rapid decrease of BuChE specific activity which takes place during normal development, whereas in the case of ALD muscle little change was observed. Moreover, the asymmetric forms which were dramatically reduced in denervated PLD muscle were virtually absent in denervated ALD muscle at day 14. Denervated PLD and ALD muscles were stimulated from day 4 to day 14 of age. Two patterns of stimulation were applied, either 5-Hz frequency (slow rhythm) or 40-Hz frequency (fast rhythm). Both patterns of stimulation provided the same number of impulses per day (about 61,000). In PLD muscle, electrical stimulation almost totally prevented the postdenervation loss in asymmetric forms and led to a decrease in BuChE specific activity. In ALD muscle, electrical stimulation partially prevented the asymmetric form loss which occurs after denervation. This study emphasizes the role of evoked muscle activity in the regulation of BuChE asymmetric forms in the fast PLD muscle and the differential response of denervated slow and fast muscles to electrical stimulation.

  3. 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.

  4. Water Extractable Phytochemicals from Peppers (Capsicum spp. Inhibit Acetylcholinesterase and Butyrylcholinesterase Activities and Prooxidants Induced Lipid Peroxidation in Rat Brain In Vitro

    Directory of Open Access Journals (Sweden)

    Omodesola O. Ogunruku

    2014-01-01

    Full Text Available Background. This study sought to investigate antioxidant capacity of aqueous extracts of two pepper varieties (Capsicum annuum var. accuminatum (SM and Capsicum chinense (RO and their inhibitory effect on acetylcholinesterase and butyrylcholinesterase activities. Methods. The antioxidant capacity of the peppers was evaluated by the 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid (ABTS radical scavenging ability and ferric reducing antioxidant property. The inhibition of prooxidant induced lipid peroxidation and cholinesterase activities in rat brain homogenates was also evaluated. Results. There was no significant difference (P>0.05 in the total phenol contents of the unripe and ripe Capsicum spp. extracts. Ripe and unripe SM samples had significantly higher (P<0.05 ABTS* scavenging ability than RO samples, while the ripe fruits had significantly higher (P<0.05 ferric reducing properties in the varieties. Furthermore, the extracts inhibited Fe2+ and quinolinic acid induced lipid peroxidation in rats brain homogenates in a dose-dependent manner. Ripe and unripe samples from SM had significantly higher AChE inhibitory abilities than RO samples, while there was no significant difference in the BuChE inhibitory abilities of the pepper samples. Conclusion. The antioxidant and anticholinesterase properties of Capsicum spp. may be a possible dietary means by which oxidative stress and symptomatic cognitive decline associated with neurodegenerative conditions could be alleviated.

  5. The first synthesis of 4-phenylbutenone derivative bromophenols including natural products and their inhibition profiles for carbonic anhydrase, acetylcholinesterase and butyrylcholinesterase enzymes.

    Science.gov (United States)

    Bayrak, Çetin; Taslimi, Parham; Gülçin, İlhami; Menzek, Abdullah

    2017-06-01

    The first synthesis of (E)-4-(3-bromo-4,5-dihydroxyphenyl)but-3-en-2-one (1), (E)-4-(2-bromo-4,5-dihydroxyphenyl)but-3-en-2-one (2), and (E)-4-(2,3-dibromo-4,5-dihydroxyphenyl)but-3-en-2-one (3) was realized as natural bromophenols. Derivatives with mono OMe of 2 and 3 were obtained from the reactions of their derivatives with di OMe with AlCl3. These novel 4-phenylbutenone derivatives were effective inhibitors of the cytosolic carbonic anhydrase I and II isoenzymes (hCA I and II), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with Ki values in the range of 158.07-404.16pM for hCA I, 107.63-237.40pM for hCA II, 14.81-33.99pM for AChE and 5.64-19.30pM for BChE. The inhibitory effects of the synthesized novel 4-phenylbutenone derivatives were compared to acetazolamide as a clinical hCA I and II isoenzymes inhibitor and tacrine as a clinical AChE and BChE enzymes inhibitor. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Design, Synthesis, and Biological Evaluation of a New Series of Biphenyl/Bibenzyl Derivatives Functioning as Dual Inhibitors of Acetylcholinesterase and Butyrylcholinesterase

    Directory of Open Access Journals (Sweden)

    Dong-mei Wang

    2017-01-01

    Full Text Available Alzheimer’s disease (AD, the most common form of dementia in adults, is a progressive neurodegenerative disorder of the brain characterized by loss of memory and steady deterioration of cognition. Here, a series of symmetrical molecules containing biphenyl/bibenzyl scaffolds (12–36 were designed, synthesized, and evaluated for their ability to inhibit both acetylcholinesterase (AChE and butyrylcholinesterase (BuChE. A biological evaluation showed that most of these biphenyl derivatives were potent AChE and BuChE inhibitors. Among them, compound 15 displayed the greatest ability to inhibit BuChE (IC50 = 0.74 µM and was also a good AChE inhibitor (IC50 = 1.18 µM. Compound 19 was not only a potent AChE inhibitor (IC50 = 0.096 µM, but also a mild BuChE inhibitor (IC50 =1.25 µM. Overall, these results suggested that compound 19 may be a promising agent in the treatment of AD.

  7. Administering social security: challenges yesterday and today.

    Science.gov (United States)

    Puckett, Carolyn

    2010-01-01

    In 2010, the Social Security Administration (SSA) celebrates the 75th anniversary of the passage of the Social Security Act. In those 75 years, SSA has been responsible for programs providing unemployment insurance, child welfare, and supervision of credit unions, among other duties. This article focuses on the administration of the Old-Age, Survivors, and Disability Insurance program, although it also covers some of the other major programs SSA has been tasked with administering over the years-in particular, Medicare, Black Lung benefits, and Supplemental Security Income. The article depicts some of the challenges that have accompanied administering these programs and the steps that SSA has taken to meet those challenges. Whether implementing complex legislation in short timeframes or coping with natural disasters, SSA has found innovative ways to overcome problems and has evolved to meet society's changing needs.

  8. 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

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

    Science.gov (United States)

    Kandiah, Nagaendran; Pai, Ming-Chyi; Senanarong, Vorapun; Looi, Irene; Ampil, Encarnita; Park, Kyung Won; Karanam, Ananda Krishna; Christopher, Stephen

    2017-01-01

    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 AChE-BuChE inhibitory activity of rivastigmine as a therapeutic strategy in the treatment of neurological disorders, with a focus on the role of rivastigmine in subcortical dementias such as vascular dementia (VaD) and PDD. Toward this objective, we performed a literature search in PubMed and Ovid with limits to articles published in the English language before June 2016. The available evidence from the literature suggests that the dual inhibition of AChE and BuChE may afford additional therapeutic potential of rivastigmine in subcortical dementias (subcortical VaD and PDD) with benefits on cognition and behavioral symptoms. Rivastigmine was found to specifically benefit executive dysfunction frequently observed in subcortical dementias; however, large randomized clinical studies are warranted to support these observations.

  10. 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.

  11. The radiation dosimetry of intrathecally administered radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Stabin, M.G. [Oak Ridge Inst. for Science and Education, TN (United States); Evans, J.F. [Ohio State Univ., Columbus, OH (United States)

    1999-01-01

    The radiation dose to the spine, spinal cord, marrow, and other organs of the body from intrathecal administration of several radiopharmaceuticals was studied. Anatomic models were developed for the spine, spinal cerebrospinal fluid (CSF), spinal cord, spinal skeleton, cranial skeleton, and cranial CSF. A kinetic model for the transport of CSF was used to determine residence times in the CSF; material leaving the CSF was thereafter assumed to enter the bloodstream and follow the kinetics of the radiopharmaceutical as if intravenously administered. The radiation transport codes MCNP and ALGAMP were used to model the electron and photon transport and energy deposition. The dosimetry of Tc-99m DTPA and HSA, In-111 DTPA, I-131 HSA, and Yb-169 DTPA was studied. Radiation dose profiles for the spinal cord and marrow in the spine were developed and average doses to all other organs were estimated, including dose distributions within the bone and marrow.

  12. How to administer lidocaine in wounds.

    Science.gov (United States)

    Welsh, Jeanette; Rowe, Graham

    2017-09-20

    Before a wound can be cleaned and/or closed, the use of a local anaesthetic such as lidocaine is often required to enable the nurse to assess the wound thoroughly and plan the optimal method of repair. This article explains how to administer lidocaine safely and effectively, including how to infiltrate a wound with lidocaine before cleaning or suturing. There are potentially serious consequences associated with the use of local anaesthesia, but careful preparation will ensure patient safety and contribute towards a positive patient experience. How to articles can help to update your practice and ensure it remains evidence-based. Apply this article to your practice. Reflect on and write a short account of. ©2012 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

  13. 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.

  14. Selective in vitro and in silico butyrylcholinesterase inhibitory activity of diterpenes and rosmarinic acid isolated from Perovskia atriplicifolia Benth. and Salvia glutinosa L.

    Science.gov (United States)

    Senol, F Sezer; Ślusarczyk, Sylwester; Matkowski, Adam; Pérez-Garrido, Alfonso; Girón-Rodríguez, Francisco; Cerón-Carrasco, José P; den-Haan, Helena; Peña-García, Jorge; Pérez-Sánchez, Horacio; Domaradzki, Krzysztof; Orhan, Ilkay Erdogan

    2017-01-01

    Cholinesterase inhibition is one of the most treatment strategies against Alzheimer's disease (AD) where metal accumulation is also strongly associated with pathology of the disease. In the current study, we assessed inhibitory effect against acetyl- (AChE) and butyrylcholinesterase (BChE) and metal-chelating capacity of twelve diterpenes: arucadiol, miltirone, tanshinone IIa, 1-oxomiltirone, cryptotanshinone, 1,2-didehydromiltirone, 1,2-didehydrotanshinone IIa, 1β-hydroxycryptotanshinone, 15,16-dihydrotanshinone, tanshinone I, isotanshinone II, 1(S)-hydroxytanshinone IIa, and rosmarinic acid, isolated from Perovskia atriplicifolia and Salvia glutinosa. The compounds were tested at 10 μg/mL using ELISA microtiter assays against AChE and BChE. QSAR and molecular docking studies have been also performed on the active compounds. All of the compounds showed higher [e.g., IC50 = 1.12 ± 0.07 μg/mL for 1,2-didehydromiltirone, IC50 = 1.15 ± 0.07 μg/mL for cryptotanshinone, IC50 = 1.20 ± 0.03 μg/mL for arucadiol, etc.)] or closer [1,2-didehydrotanshinone IIa (IC50 = 5.98 ± 0.49 μg/mL) and 1(S)-hydroxytanshinone IIa (IC50 = 5.71 ± 0.27 μg/mL)] inhibition against BChE as compared to that of galanthamine (IC50 = 12.56 ± 0.37 μg/mL), whereas only 15,16-dihydrotanshinone moderately inhibited AChE (65.17 ± 1.39%). 1,2-Didehydrotanshinone IIa (48.94 ± 0.26%) and 1(S)-hydroxytanshinone IIa (47.18 ± 5.10%) possessed the highest metal-chelation capacity. The present study affords an evidence for the fact that selective BChE inhibitors should be further investigated as promising candidate molecules for AD therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. The kinetic study of the inhibition of human cholinesterases by demeton-S-methyl shows that cholinesterase-based titration methods are not suitable for this organophosphate.

    Science.gov (United States)

    Bazire, Alexandre; Gillon, Emilie; Lockridge, Oksana; Vallet, Virginie; Nachon, Florian

    2011-04-01

    The organophosphorus insecticide, demeton-S-methyl (DSM), is considered as a good surrogate of the highly toxic nerve agent VX for skin absorption studies due to similar physico-chemical properties and in vitro percutaneous penetration profile. But, when skin distribution was estimated by measuring inhibition of cholinesterase activity, the results were poorly reproducible. The various grades of commercial DSM solutions were suspected to be the origin of the discrepancies. This hypothesis was tested by measuring inhibition of human acetyl- and butyrylcholinesterase by two commercial DSM solutions. The inhibition rate was independent on the enzyme concentration confirming pseudo-first order conditions. But complete inhibition of butyrylcholinesterase activity was achieved only when the DSM concentration was at least 1500-fold higher than the enzyme concentration. Besides, complete inhibition of acetylcholinesterase was never achieved. Mass spectrometry analysis of the inhibited butyrylcholinesterase adducts identified monomethoxyphosphorylated-serine, the aged product of inhibition by DSM or a derivative with a modified leaving group. Neither spontaneous reactivation nor aging of the dimethoxyphosphorylated-serine could account for the inhibition kinetics observed, suggesting an overly complicated kinetic scheme not compatible with the requirement of a titration experiment. In conclusion, cholinesterase-based analytical methods should be avoided for DSM titration in skin penetration studies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Ease of use and preference for a new disposable self-injection pen compared with a reusable pen for administering recombinant human growth hormone: A multicenter, 2-month, single-arm, open-label clinical trial in patient-caregiver dyads.

    Science.gov (United States)

    Hey-Hadavi, Judith; Pleil, Andreas; Deeb, Larry C; Fuqua, John S; Silverman, Lawrence A; Reiner, Barry; Newfield, Ron; Rajicic, Natasa; Wajnrajch, Michael P; Cara, Jose F

    2010-11-01

    Improved ease of use of drug-delivery devices may enhance compliance. Development of an easier-to-use device for administration of recombinant human growth hormone (rhGH) may thus be beneficial for patients and their caregivers. This study compared ease of use and preference for a new disposable rhGH injection pen relative to previous experience with the currently available reusable pen in standard practice. Both pens deliver the same formulation of rhGH. This multicenter, single-arm, open-label study assessed ease of use and preference for the 2 injection pens in patient-caregiver dyads. Eligible children were aged 8 through 18 years, were currently being treated with rhGH, and had been compliant with use of the current reusable pen for ≥ 3 months before study entry. A validated self-reported Injection Pen Assessment Questionnaire was administered twice during the study-at baseline (to assess perceptions of the reusable pen) and after 2 months of use of the new disposable pen-to assess ease of use of the individual pens (rated on a 5-point Likert-type scale), the comparative ease of use of the 2 pens, and pen preference. The primary end point was the proportion of dyads who rated the new pen as no different or easier to use than the current pen. Regardless of treatment or suspected causal relationship to the investigational product, all observed or volunteered adverse events (AEs) were recorded and rated as mild, moderate, or severe. Of 137 screened dyads, 136 (91 boys, 45 girls) were included in the safety population and 133 were included in the efficacy population. The children had a mean age of 12.3 years, a mean weight of 42.2 kg, a mean height of 145.9 cm, and a mean body mass index of 19.3 kg/m(2); 84.6% of the children were white. The majority (82.4%) of adult dyad members were subjects' mothers. The adult dyad members were more likely than the child members to be responsible for preparing the injection (82.0%) and administering the injection (72

  17. Effect of orally administered probenecid on the pharmacokinetics of cefoxitin.

    OpenAIRE

    Vlasses, P H; Holbrook, A M; Schrogie, J J; Rogers, J D; Ferguson, R K; Abrams, W B

    1980-01-01

    To characterize the effect of orally administered probenecid on the pharmacokinetics of cefoxitin in healthy male volunteers, we administered to one group of six subjects 2 g of cefoxitin by intravenous (i.v.) bolus either alone, with 1 g of probenecid concomitantly, or when 1 g of probenecid was administered 1 h previously by using a crossover design. Likewise, we administered to a second group of six subjects 2 g of cefoxitin intramuscularly (i.m.) together with 1 and 2 g of probenecid. Pro...

  18. 40 CFR 147.901 - EPA-administered program.

    Science.gov (United States)

    2010-07-01

    ... lands, is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of this subpart. Injection... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Kentucky § 147.901 EPA...

  19. 40 CFR 147.751 - EPA-administered program.

    Science.gov (United States)

    2010-07-01

    ... program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, and 148 and the additional... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Indiana § 147.751 EPA-administered program. (a) Contents. The UIC program for all classes of wells on Indian lands, and for Class I...

  20. 40 CFR 147.601 - EPA-administered program.

    Science.gov (United States)

    2010-07-01

    ... administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of this subpart. Injection well owners and... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Hawaii § 147.601 EPA...

  1. 40 CFR 147.801 - EPA-administered program.

    Science.gov (United States)

    2010-07-01

    ... administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of this subpart. Injection well owners and... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Iowa § 147.801 EPA...

  2. 40 CFR 147.101 - EPA-administered program.

    Science.gov (United States)

    2010-07-01

    ... program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Alaska § 147.101 EPA-administered program. (a) Contents. The UIC program in the State of Alaska for Class I, III, IV, and V wells...

  3. 40 CFR 282.53 - Arkansas State-Administered Program.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Arkansas State-Administered Program. 282.53 Section 282.53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID... administered by the Arkansas Department of Pollution Control and Ecology, was approved by EPA pursuant to 42 U...

  4. 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.

  5. Comparison of quality of induction of anaesthesia between intramuscularly administered ketamine, intravenously administered ketamine and intravenously administered propofol in xylazine premedicated cats

    Directory of Open Access Journals (Sweden)

    T.B. Dzikiti

    2007-06-01

    Full Text Available The quality of induction of general anesthesia produced by ketamine and propofol, 2 of the most commonly used anaesthetic agents in cats, was assessed. Eighteen cats admitted for elective procedures were randomly assigned to 3 groups and then premedicated with xylazine 0.75 mg/kg intramuscularly before anaesthesia was induced with ketamine 15 mg/kg intramuscularly (KetIM group, ketamine 10 mg/kg intravenously (KetIV group or propofol 4 mg/kg intravenously (PropIV group. Quality of induction of general anaesthesia was determined by scoring ease of intubation, degree of struggling, and vocalisation during the induction period. The quality of induction of anaesthesia of intramuscularly administered ketamine was inferior to that of intravenously administered ketamine, while intravenously administered propofol showed little difference in quality of induction from ketamine administered by both the intramuscular and intravenous routes. There were no significant differences between groups in the ease of intubation scores, while vocalisation and struggling were more common in cats that received ketamine intramuscularly than in those that received intravenously administered ketamine or propofol for induction of anaesthesia. Laryngospasms occurred in 2 cats that received propofol. The heart rates and respiratory rates decreased after xylazine premedication and either remained the same or decreased further after induction for all 3 groups, but remained within normal acceptable limits. This study indicates that the 3 regimens are associated with acceptable induction characteristics, but administration of ketamine intravenously is superior to its administration intramuscularly and laryngeal desensitisation is recommended to avoid laryngospasms.

  6. 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.

  7. 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.

  8. Comparison of an interviewer-administered with an automated self-administered 24 h (ASA24) dietary recall in adolescents.

    Science.gov (United States)

    Hughes, Ashley R; Summer, Suzanne S; Ollberding, Nicholas J; Benken, Laura A; Kalkwarf, Heidi J

    2017-12-01

    The current pilot study aimed to assess whether reporting quality would decline materially in adolescents completing weekly web-based Automated Self-Administered 24-Hour dietary recalls (ASA24-Kids-2014) and interviewer-administered 24 h dietary recalls for six weeks. We also aimed to assess method preference. We conducted two studies. Study 1 (n 20) randomized participants to complete either one ASA24-Kids-2014 or one interviewer-administered recall weekly, for six weeks. Energy intake and number of foods reported were described for each method over time. Differences between recall methods for each measure were tested using mixed-effects regression. Study 2 (n 10) employed a randomized crossover design to describe method preference. Dietary intake was collected either by telephone (interviewer-administered dietary recalls) or via the Internet (ASA24-Kids-2014 dietary recalls). Adolescents aged 12-17 years with no prior diet recording experience were enrolled. In Study 1, mean (sd) total energy and number of foods reported decreased by 50 (222) kJ (12 (53) kcal) and 0·05 (0·31) items v. 38 (138) kJ (9 (33) kcal) and 0·17 (0·14) items per recall for participants randomized to the ASA24-Kids-2014 v. interviewer-administered recalls, respectively. There was no difference between groups for either measure (P > 0·57). In Study 2, eight of ten participants preferred the interviewer-administered recall over the ASA24-Kids-2014. Overall, seven of twenty participants experienced technical difficulties with the ASA24-Kids-2014. No appreciable decay in reporting quality was seen for either method. However, participants reported a preference for the interviewer-administered recall. Our findings can help inform and support larger studies to further characterize the performance of the ASA24 in adolescents.

  9. 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 ...

  10. Clinical pharmacology of carboplatin administered in combination with paclitaxel

    NARCIS (Netherlands)

    van Warmerdam, L. J.; Huizing, M. T.; Giaccone, G.; Postmus, P. E.; ten Bokkel Huinink, W. W.; van Zandwijk, N.; Koolen, M. G.; Helmerhorst, T. J.; van der Vijgh, W. J.; Veenhof, C. H.; Beijnen, J. H.

    1997-01-01

    The clinical pharmacology of carboplatin (C) administered with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (P) was investigated in two phase I studies undertaken in 83 previously untreated patients with either non-small cell lung cancer or ovarian cancer. Carboplatin was

  11. Neurotoxic profiles of vanadium when administered at the onset of ...

    African Journals Online (AJOL)

    Further “immune” assays revealed astrocytic activation (GFAP stain), demyelination (CNPase) and activated microglia (Iba1) due to vanadium which were ameliorated by the administration of vit E to the dams. The pups whose dams were administered with vit E alone showed signs of cellular degeneration which might be ...

  12. Nurse-administered femoral nerve block after hip fracture.

    Science.gov (United States)

    Cole, Andy

    Hip fracture is a common injury that predominantly affects older people. Pain following fracture of the neck of the femur is present throughout the illness trajectory, including the preoperative and postoperative periods. This article describes how nurses at one trust implemented an innovative nurse-administered femoral nerve block service.

  13. The analgesic effect of diclofenac sodium administered via the ...

    African Journals Online (AJOL)

    2016-02-08

    Feb 8, 2016 ... Drug Industry and Trade Company, Istanbul, Turkey was administered intraperitoneally to all rats for 5 days. Formation of groups and drug ..... Siegmund E, Cadmus R, Lu G. Screening of analgesics, including aspirin‑type compounds, based upon the antagonism of chemically induced writhing in mice.

  14. Erythrocyte osmotic fragility of pigs administered ascorbic acid and ...

    African Journals Online (AJOL)

    PRECIOUS

    2010-01-11

    Jan 11, 2010 ... The experiment was carried out with the aim of investigating the effect of an antioxidant ascorbic acid on erythrocyte osmotic fragility of pigs transported by road for 4 h during the harmattan season. 16 pigs administered with ascorbic acid at the dose of 250 mg/kg per os and individually served as.

  15. 40 CFR 147.151 - EPA-administered program.

    Science.gov (United States)

    2010-07-01

    ... Navajo Indian lands consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of this subpart. Injection well owners and operators, and... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Arizona § 147.151 EPA...

  16. 40 CFR 147.451 - EPA-administered program.

    Science.gov (United States)

    2010-07-01

    ... requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of this subpart. Injection well owners and operators, and EPA shall comply with these requirements. (b... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS District of Columbia...

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

    African Journals Online (AJOL)

    TUOYO

    2010-08-09

    Aug 9, 2010 ... 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.

  18. Effect of Orally Administered Zingiber Officinale on the Intra Ocular ...

    African Journals Online (AJOL)

    PURPOSE: To determine the therapeutic effect of Ginger (Zingiber officinale) on increased intraocular pressure (IOP). METHODS: Twenty male and female New Zealand rabbits divided into 5 groups (A, B, C, D and E) were used. Groups B and D were administered with topical atropine 1% for 2 weeks while groups A and C ...

  19. Impact of Methods of Administering Growth-Stage Deficit Irrigation ...

    African Journals Online (AJOL)

    Agricultural Research, Samaru Zaria, to assess the impact of two methods of administering Growth-stage deficit irrigation ..... Table 6: Biomass yield, grain yield and harvest index of the maize (SAMAS TZEE) crop in 2009/10 season. 2009/10 season. 2010/11 season. Treatment Class. Treatment label. GY (t/ha) BY (t/ha). HI.

  20. Teaching Auction Strategy Using Experiments Administered Via the Internet

    Science.gov (United States)

    Asker, John; Grosskopf, Brit; McKinney, C. Nicholas; Niederle, Muriel; Roth, Alvin E.; Weizsacker, Georg

    2004-01-01

    The authors present an experimental design used to teach concepts in the economics of auctions and implications for e-Business procurement. The experiment is easily administered and can be adapted to many different treatments. The chief innovation is that it does not require the use of a lab or class time. Instead, the design can be implemented on…

  1. Changes in activities of tissues enzymes in rats administered Ficus ...

    African Journals Online (AJOL)

    This study evaluates the effects of methanolic extract of Ficus exasperata leaf on the activities of some enzymes in the serum, liver, kidney and heart of albino rats. Twenty four rats were sorted into four groups: Group A (control) received distilled water while rats in groups B, C and D were administered graded doses.

  2. Biochemical effects on the liver and kidney of rats administered ...

    African Journals Online (AJOL)

    The effects of aqueous extract of ximenia Americana stem bark on liver and kidney of albino rats was investigated. Different doses of the crude extract were administered to rats for 30 consecutive days. The levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of treated animals significantly ...

  3. 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 ...

  4. Challenges of Administering Teacher Education Programme in Kenyan Universities

    Science.gov (United States)

    Genvieve, Nasimiyu

    2017-01-01

    Proper management of logistical issues in Teacher education programme tends to promote the quality of preparation of school teachers. The main objective of the study was to investigate challenges of administering teacher education programmes in Kenyan universities. The theoretical framework of the study was adopted as used by Koehler and Mishra's…

  5. 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 ...

  6. 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 ...

  7. Erythrocyte osmotic fragility of pigs administered ascorbic acid and ...

    African Journals Online (AJOL)

    The experiment was carried out with the aim of investigating the effect of an antioxidant ascorbic acid on erythrocyte osmotic fragility of pigs transported by road for 4 h during the harmattan season. 16 pigs administered with ascorbic acid at the dose of 250 mg/kg per os and individually served as experimental animals and ...

  8. 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....... Secondary outcomes included the number of patients with reduction in pain intensity during transport (NRS ≥ 2), the number of patients with NRS > 3 at hospital arrival, and potential fentanyl-related side effects. RESULTS: Fentanyl reduced pain from before treatment (8, IQR 7-9) to hospital arrival (4, IQR...

  9. The use of subconjunctivally administered tissue plasminogen activator after trabeculectomy.

    Science.gov (United States)

    Piltz, J R; Starita, R J

    1994-01-01

    Blockage of aqueous flow in the early postoperative period can be devastating to the success of trabeculectomy. We used tissue plasminogen activator (tPA) subconjunctivally in an attempt to release a trabeculectomy flap that appeared to be adherent to its scleral bed. No change was noted 90 minutes after injection, but a highly elevated bleb was present on the first postoperative day. Subconjunctivally administered tPA may be useful in releasing the fibrin "glue" in cases with adherent trabeculectomy flaps.

  10. The Effect of Alternative E-Mail Contact Timing Strategies on Response Rates in a Self-Administered Web Survey

    Science.gov (United States)

    Lewis, Taylor; Hess, Karl

    2017-01-01

    The Federal Employee Viewpoint Survey is an annual survey of over 800,000 permanently employed civilian personnel from 87 agencies. First administered in 2002, the web-based survey measures a broad range of employee perceptions, attitudes, and behaviors, serving as a valuable tool for human resources managers to determine which aspects of an…

  11. Nurses and subordination: a historical study of mental nurses’ perceptions on administering aversion therapy for ‘sexual deviations’

    Science.gov (United States)

    Dickinson, Tommy; Cook, Matt; Playle, John; Hallett, Christine

    2014-01-01

    Nurses and subordination: a historical study of mental nurses’ perceptions on administering aversion therapy for ‘sexual deviations’ This study aimed to examine the meanings that nurses attached to the ‘treatments’ administered to cure ‘sexual deviation’ (SD) in the UK, 1935–1974. In the UK, homosexuality was considered a classifiable mental illness that could be ‘cured’ until 1992. Nurses were involved in administering painful and distressing treatments. The study is based on oral history interviews with fifteen nurses who had administered treatments to cure individuals of their SD. The interviews were transcribed for historical interpretation. Some nurses believed that their role was to passively follow any orders they had been given. Other nurses limited their culpability concerning administering these treatments by adopting dehumanising and objectifying language and by focussing on administrative tasks, rather than the human beings in need of their care. Meanwhile, some nurses genuinely believed that they were acting beneficently by administering these distinctly unpleasant treatments. It is envisaged that this study might act to reiterate the need for nurses to ensure their interventions have a sound evidence base and that they constantly reflect on the moral and value base of their practice and the influence that science and societal norms can have on changing views of what is considered ‘acceptable practice’. PMID:23876127

  12. Fetal Tachycardia Treated Successfully with Maternally Administered Propylthiouracil

    Directory of Open Access Journals (Sweden)

    Barbara V. Parilla

    2014-01-01

    Full Text Available Background. Fetal tachycardia may result from the transplacental passage of thyroid stimulating immunoglobulins in a patient with hypothyroidism secondary to ablation of Graves’ disease. Case. A 32-year-old woman, gravida 4, para 2, and abortus 1, with hypothyroidism and a history of Graves’ disease, presented at 23 6/7 weeks of gestation with a persistent fetal tachycardia. The treatment of the fetal tachycardia with maternally administered digoxin and Sotalol was unsuccessful. Maternal thyroid stimulating immunoglobulins were elevated, and treatment with maternally administered propylthiouracil (PTU resulted in a normal sinus rhythm for the remainder of the pregnancy. An induction of labor was performed at 37 weeks. Four to five days after delivery, the neonate exhibited clinical signs of hyperthyroidism necessitating treatment. Conclusion. Fetal tachycardia resulting from the transplacental passage of thyroid stimulating immunoglobulins can be successfully treated with maternally administered PTU. The neonate needs to be followed up closely as clinical signs of hyperthyroidism may occur as thyroid stimulating immunoglobulins continue to circulate in the neonate, while the serum levels of PTU decline.

  13. Absorption sites of orally administered drugs in the small intestine.

    Science.gov (United States)

    Murakami, Teruo

    2017-12-01

    In pharmacotherapy, drugs are mostly taken orally to be absorbed systemically from the small intestine, and some drugs are known to have preferential absorption sites in the small intestine. It would therefore be valuable to know the absorption sites of orally administered drugs and the influencing factors. Areas covered:In this review, the author summarizes the reported absorption sites of orally administered drugs, as well as, influencing factors and experimental techniques. Information on the main absorption sites and influencing factors can help to develop ideal drug delivery systems and more effective pharmacotherapies. Expert opinion: Various factors including: the solubility, lipophilicity, luminal concentration, pKa value, transporter substrate specificity, transporter expression, luminal fluid pH, gastrointestinal transit time, and intestinal metabolism determine the site-dependent intestinal absorption. However, most of the dissolved fraction of orally administered drugs including substrates for ABC and SLC transporters, except for some weakly basic drugs with higher pKa values, are considered to be absorbed sequentially from the proximal small intestine. Securing the solubility and stability of drugs prior to reaching to the main absorption sites and appropriate delivery rates of drugs at absorption sites are important goals for achieving effective pharmacotherapy.

  14. Intestinal absorption of coenzyme Q(10) administered in a meal or as capsules to healthy subjects

    DEFF Research Database (Denmark)

    Weber, Christine; Bysted, Anette; Hølmer, Gunhild Kofoed

    1997-01-01

    A randomized cross-over study by supplementation with single doses of coenzyme Q(10) (30 mg/person), administered either as a meal consisting of cooked pork heart or as 30 mg coenzyme Q(10) capsules was performed to investigate the bioavailability of dietary coenzyme Q(10) in humans. The increase...... in serum coenzyme Q(10) concentration was used as an index of the absorption, and reached a maximum six hours after the ingestion of either meal or capsules. Following intake of coenzyme Q(10) capsules, the serum coenzyme Q(10) concentrations increased significantly (p...

  15. Administering and monitoring high-alert medications in acute care.

    Science.gov (United States)

    Cajanding, Joseph Macale Ruff

    2017-07-19

    The nurse's primary role in the medication process is to ensure that drugs are administered safely to patients, thus reducing the risk of unnecessary harm or injury. High-alert medications are a particular concern for healthcare professionals, since they are associated with an increased risk of causing patient harm. This article identifies high-risk medications and outlines measures that can be used to prevent potential harm to patients as a result of these medications, including computerised provider order entry, Tall Man lettering, order sets, independent double-checks and proactive patient monitoring.

  16. Enabling carers to administer depot injections: an action research study

    OpenAIRE

    Crowley, John J.

    2014-01-01

    This study has its origins in a question posed by a patient diagnosed with a psychotic illness, as to why her husband could not administer depot injection. Following local and national discussion the study aims were;\\ud \\ud - to explore the elements of risk management involved in enabling carers (supportive persons) to give depot injections\\ud \\ud - to develop a training package that may be useful for others to use should such a request be made\\ud \\ud - to establish whether enabling supportiv...

  17. Nursing students administering medication: appreciating and seeking appropriate supervision.

    Science.gov (United States)

    Reid-Searl, Kerry; Moxham, Lorna; Walker, Sandra; Happell, Brenda

    2010-03-01

    This paper is a report of a study of undergraduate nursing students' experience of administering medication in the clinical setting. Safe administration of medication is an important component of skilled nursing practice, and nursing students require personal and supportive supervision from Registered Nurses to enhance learning and promote safety. A review of the literature revealed a lack of research addressing students' experiences in administering medication. A grounded theory methodology was used. In-depth semi-structured interviews were conducted with a convenience sample of 27 undergraduate nursing students in Queensland Australia in 2005. Supervision emerged as the central category in this study. Participants acknowledged the need for and importance of supervision according to the following sub-themes: a university requirement; scope of practice; and safety, the five rights. They also described behaviours they adopted to seek supervision, including negotiating, chasing, waiting and avoiding. Universities and healthcare settings need to collaborate more closely to ensure that adequate supervision is provided to ensure safe practices.

  18. Metabolic fate of orally administered enzymatically synthesized glycogen in rats.

    Science.gov (United States)

    Furuyashiki, Takashi; Takata, Hiroki; Kojima, Iwao; Kuriki, Takashi; Fukuda, Itsuko; Ashida, Hitoshi

    2011-04-01

    We developed a new process for enzymatically synthesized glycogen (ESG), which is equivalent in physicochemical properties to natural-source glycogen (NSG) except its resistant property to degradation by α-amylase in vitro. In this study the metabolic fates of orally administered ESG in rats were investigated by a single oral administration test and a 2 week ingestion test. The glycemic index of ESG was 79. After the 2 week ingestion of ESG, the cecal content and production of short chain fatty acids were significantly increased, the pH value of cecal content was lowered, and the counts of Bifidobacterium and Lactobacillus in feces were significantly increased. Additionally, plasma levels of triacylglycerol and total cholesterol were significantly reduced by ESG. In contrast, NSG did not affect these parameters at all. The results collectively suggest that around 20% of orally administered ESG was transferred to the cecum in the form of polymer and assimilated into short chain fatty acids by microbiota and the polymer affected lipid metabolism.

  19. Use of oromucosally administered interferon-alpha in the prevention and treatment of animal diseases.

    Science.gov (United States)

    Dec, M; Puchalski, A

    2008-01-01

    Interferon-alpha (IFN-alpha) is well known as a clinically effective antiviral and antineoplastic therapeutic agent. It has also been shown to have immunoregulatory properties. IFN-alpha stimulates a cell-mediated innate immune response and then participates in the transition of the initial host innate response to an effective adaptive immune response. IFN-alpha is produced in small quantities in nasal secretions during viral infections, prompting many authors to suggest that low-dose oromucosal administration of IFN-alpha effectively mimics nature. Moreover, the injectable high-dose interferon therapy currently approved for various human disorders causes numerous side effects. By contrast, oromucosal administration of IFN-alpha is not associated with toxic effects. Another distinct advantage is ease of administration: the IFN can be dissolved in drinking water or administered by nebulization to the oral or nasal cavity. This review describes the current state of knowledge concerning orally administered IFN-alpha, of both human and animal origin, as a prophylactic or therapeutic agent in veterinary medicine. We present the effects of IFN-alpha in such animals as cattle, pigs, horses, cats, dogs and chickens, and attempt to explain its mechanism of action following oromucosal administration. It is hoped that this review of the medical literature on the use of IFN-alpha in animals will give practitioners a better understanding of the challenges and benefits of using this interesting cytokine in clinical practice.

  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. 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

  2. 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...... as patients developing an adverse event (oxygen saturation 30% or a drop in systolic blood pressure of > 50 mmHg). The remaining patients served as controls. RESULTS: A total of 6,840 consecutive patients undergoing 7,364 procedures were included. The mean propofol...... dose was 331.6 mg (standard deviation = 179.4 mg). The overall rate of hypoxia was 3.2%, and the rate of hypotension was 3.1%. Assisted ventilation was needed in 0.5%. Age (p propofol dose (p = 0.001) were associated...

  3. An overview of self-administered health literacy instruments.

    Directory of Open Access Journals (Sweden)

    Braden O Neill

    Full Text Available With the increasing recognition of health literacy as a worldwide research priority, the development and refinement of indices to measure the construct is an important area of inquiry. Furthermore, the proliferation of online resources and research means that there is a growing need for self-administered instruments. We undertook a systematic overview to identify all published self-administered health literacy assessment indices to report their content and considerations associated with their administration. A primary aim of this study was to assist those seeking to employ a self-reported health literacy index to select one that has been developed and validated for an appropriate context, as well as with desired administration characteristics. Systematic searches were carried out in four electronic databases, and studies were included if they reported the development and/or validation of a novel health literacy assessment measure. Data were systematically extracted on key characteristics of the instruments: breadth of construct ("generic" vs. "content- or context- specific" health literacy, whether it was an original instrument or a derivative, country of origin, administration characteristics, age of target population (adult vs. pediatric, and evidence for validity. 35 articles met the inclusion criteria. There were 27 original instruments (27/35; 77.1% and 8 derivative instruments (8/35; 22.9%. 22 indices measured "general" health literacy (22/35; 62.9% while the remainder measured condition- or context- specific health literacy (13/35; 37.1%. Most health literacy measures were developed in the United States (22/35; 62.9%, and about half had adequate face, content, and construct validity (16/35; 45.7%. Given the number of measures available for many specific conditions and contexts, and that several have acceptable validity, our findings suggest that the research agenda should shift towards the investigation and elaboration of health literacy

  4. 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.

  5. An Overview of Self-Administered Health Literacy Instruments

    Science.gov (United States)

    O′Neill, Braden; Gonçalves, Daniela; Ricci-Cabello, Ignacio; Ziebland, Sue; Valderas, Jose

    2014-01-01

    With the increasing recognition of health literacy as a worldwide research priority, the development and refinement of indices to measure the construct is an important area of inquiry. Furthermore, the proliferation of online resources and research means that there is a growing need for self-administered instruments. We undertook a systematic overview to identify all published self-administered health literacy assessment indices to report their content and considerations associated with their administration. A primary aim of this study was to assist those seeking to employ a self-reported health literacy index to select one that has been developed and validated for an appropriate context, as well as with desired administration characteristics. Systematic searches were carried out in four electronic databases, and studies were included if they reported the development and/or validation of a novel health literacy assessment measure. Data were systematically extracted on key characteristics of the instruments: breadth of construct (“generic” vs. “content- or context- specific” health literacy), whether it was an original instrument or a derivative, country of origin, administration characteristics, age of target population (adult vs. pediatric), and evidence for validity. 35 articles met the inclusion criteria. There were 27 original instruments (27/35; 77.1%) and 8 derivative instruments (8/35; 22.9%). 22 indices measured “general” health literacy (22/35; 62.9%) while the remainder measured condition- or context- specific health literacy (13/35; 37.1%). Most health literacy measures were developed in the United States (22/35; 62.9%), and about half had adequate face, content, and construct validity (16/35; 45.7%). Given the number of measures available for many specific conditions and contexts, and that several have acceptable validity, our findings suggest that the research agenda should shift towards the investigation and elaboration of health literacy

  6. NCBI nr-aa BLAST: CBRC-XTRO-01-3294 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-XTRO-01-3294 ref|NP_000046.1| butyrylcholinesterase precursor [Homo sapiens] s...p|P06276|CHLE_HUMAN Cholinesterase precursor (Acylcholine acylhydrolase) (Choline esterase II) (Butyrylcholi...ne esterase) (Pseudocholinesterase) gb|AAA98113.1| cholinesterase (EC 3.1.1.8) gb|AAA52015.1| butyrylcholinest...erase (EC 3.1.1.8) gb|AAA99296.1| butyrylcholinesterase gb|AAH18141.1| Butyrylcholinest...erase [Homo sapiens] gb|ABM81967.1| butyrylcholinesterase [synthetic construct] gb|ABM85146.1| butyrylcholinesterase [synthetic construct] NP_000046.1 1e-131 48% ...

  7. NCBI nr-aa BLAST: CBRC-ACAR-01-0720 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-ACAR-01-0720 ref|NP_000046.1| butyrylcholinesterase precursor [Homo sapiens] s...p|P06276|CHLE_HUMAN Cholinesterase precursor (Acylcholine acylhydrolase) (Choline esterase II) (Butyrylcholi...ne esterase) (Pseudocholinesterase) gb|AAA98113.1| cholinesterase (EC 3.1.1.8) gb|AAA52015.1| butyrylcholinest...erase (EC 3.1.1.8) gb|AAA99296.1| butyrylcholinesterase gb|AAH18141.1| Butyrylcholinest...erase [Homo sapiens] gb|ABM81967.1| butyrylcholinesterase [synthetic construct] gb|ABM85146.1| butyrylcholinesterase [synthetic construct] NP_000046.1 1e-108 42% ...

  8. Assessing planning and set-shifting abilities in autism: are experimenter-administered and computerised versions of tasks equivalent?

    Science.gov (United States)

    Williams, David; Jarrold, Christopher

    2013-12-01

    Across studies, analysis of performance on classic measures of executive functioning (EF) among individuals with autism spectrum disorder (ASD) suggests that people with this disorder may be impaired only when tasks are experimenter-administered, but not when the same tasks are computer-administered. This would imply that the underlying cause of apparent executive dysfunction in ASD is a diminished ability to engage with another person/comprehend what another person expects, rather than a diminution of the control processes that typically underpin EF task performance. However, this suggestion is limited because, to our knowledge, no study has directly compared the equivalence of computer-administered and standard experimenter-administered versions of EF tasks that have been presented in counterbalanced order among a common sample of individuals with ASD. In the current study, 21 children with ASD and 22 age- and intelligence quotient (IQ)-matched comparison participants completed, in counterbalanced order, computerised and manual versions of both a planning task and a cognitive flexibility/set-shifting task. Contrary to expectation, results indicated that participants with ASD were equally impaired in terms of the key dependent variable on standard and computerised versions of both tasks. Practically, these results suggest that computer-administered and experimenter-administered versions of planning and set-shifting tasks are equivalent among individuals with ASD and can be used interchangeably in studies of EF among this population. Theoretically, these results challenge the notion that poor performance on EF tasks among school-aged children with ASD is only the result of a limited ability to engage with a human experimenter/comprehend socially presented rules. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

  9. 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.

  10. [What lipid emulsion should be administered to ICU patients?].

    Science.gov (United States)

    Kreymann, G

    2014-01-01

    The review deals with a question what lipid emulsion should be administered to ICU patients according to recently published official parenteral and enteral nutrition guidelines. Classic lipid emulsions based on omega-6 fatty acids are immunosuppressive and should not be used with ICU patients. The olive/soy emulsion is immunoneutral and can be used for most patients. Many ICU patients are in an inflammatory state (e.g. sepsis, ARDS, pancreatitis). A common belief is that this "hyperinflammed patient population" would profit from an anti-inflammatory lipid component of their parenteral nutrition solution, such as fish oil. On the other hand, every anti-inflammatory therapy has the disadvantage of also being immunosuppressive. Inflammation is a necessary part of the host defense against infection and any correct anti-inflammatory medication presupposes the exact immunologic knowledge that there is too much inflammation for a given situation. This "too much" is certainly not fulfilled in every patient with sepsis, ARDS or pancreatitis. At the bedside it is nearly impossible to determine the degree of "hyper" inflammation. In reality, a number of these patients may be adequately inflamed or, in fact, even hypoinflammed. Specific emulsions which can be used in hyper- or hypoinflammation should be developed in the future. As long as these difficulties in the immunologic diagnosis prevail, the clinician might be best advised to use an immunoneutral lipid emulsion when choosing a lipid preparation for the ICU patients.

  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. Metapragmatics of Administering Justice in Russian and English Judicial Discourse

    Directory of Open Access Journals (Sweden)

    Татьяна Викторовна Дубровская

    2017-12-01

    Full Text Available This paper is intended as a contribution to a body of research on metapragmatics in courtroom settings, particularly in Russian and English judicial discourse, and presents the results of functional analysis of metapragmatic elements. In the article, I claim that meta-utterances are inherent in judicial discourse and perform specific functions that are essential for practising judicial power and discretion in court as well as administering justice. The paper discusses functions of meta-utterances as they are presented in recent scholarship and offers a three-group classification of metapragmatic elements in judicial discourse, according to the types of reality distinguished in (Gibbons 2003. The first group contributes to constructing the primary reality, i.e. the reality of the courtroom; the second group assists in framing the secondary reality, i.e. the reality of the crime or misdemeanor; the third group deals with framing the legal reality. Altogether, these groups of metapragmatic elements construct an organizational frame for the trial. Data for the analysis are drawn from a few trial transcripts of modern Russian and English cases (1998-2008. By using Russian and English data for the analysis, it is demonstrated that the principal functions of judicial meta-utterances are marked by parallelism in Russian and English, while minor differences discovered are related to some other pragmatic categories, e.g. politeness, that are more nationally and culturally specific.

  13. 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...

  14. Behavioral effects of urotensin-II centrally administered in mice.

    Science.gov (United States)

    Do-Rego, Jean-Claude; Chatenet, David; Orta, Marie-Hélène; Naudin, Bertrand; Le Cudennec, Camille; Leprince, Jérôme; Scalbert, Elizabeth; Vaudry, Hubert; Costentin, Jean

    2005-11-01

    Urotensin-II (U-II) receptors are widely distributed in the central nervous system. Intracerebroventricular (i.c.v.) injection of U-II causes hypertension and bradycardia and stimulates prolactin and thyrotropin secretion. However, the behavioral effects of centrally administered U-II have received little attention. In the present study, we tested the effects of i.c.v. injections of U-II on behavioral, metabolic, and endocrine responses in mice. Administration of graded doses of U-II (1-10,000 ng/mouse) provoked: (1) a dose-dependent reduction in the number of head dips in the hole-board test; (2) a dose-dependent reduction in the number of entries in the white chamber in the black-and-white compartment test, and in the number of entries in the central platform and open arms in the plus-maze test; and (3) a dose-dependent increase in the duration of immobility in the forced-swimming test and tail suspension test. Intracerebroventricular injection of U-II also caused an increase in: food intake at doses of 100 and 1,000 ng/mouse, water intake at doses of 100-10,000 ng/mouse, and horizontal locomotion activity at a dose of 10,000 ng/mouse. Whatever was the dose, the central administration of U-II had no effect on body temperature, nociception, apomorphine-induced penile erection and climbing behavior, and stress-induced plasma corticosterone level. Taken together, the present study demonstrates that the central injection of U-II at doses of 1-10,000 ng/mouse induces anxiogenic- and depressant-like effects in mouse. These data suggest that U-II may be involved in some aspects of psychiatric disorders.

  15. Pharmacokinetics and pharmacodynamics of midazolam administered as a concentrated intranasal spray. A study in healthy volunteers.

    NARCIS (Netherlands)

    Knoester, P.D.; Jonker, D.M.; Hoeven, R.T. van der; Vermeij, T.A.; Edelbroek, P.M.; Brekelmans, G.J.; Haan, G.J. de

    2002-01-01

    AIMS: To investigate the pharmacokinetic and pharmacodynamic profile of midazolam administered as a concentrated intranasal spray, compared with intravenous midazolam, in healthy adult subjects. METHODS: Subjects were administered single doses of 5 mg midazolam intranasally and intravenously in a

  16. 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

  17. Experience with Subgam, a Subcutaneously Administered Human Normal Immunoglobulin (ClinicalTrials.gov--NCT02247141.

    Directory of Open Access Journals (Sweden)

    Clive Dash

    Full Text Available A multi-centre, non-comparative study examining the efficacy and safety of Subgam, a normal immunoglobulin (IgG given weekly as a rapid subcutaneous infusion to patients with primary immune deficiency (PID, is reported. Also included is a summary of adverse drug reactions associated with the use of marketed Subgam in the UK.50 patients with stable PID on IgG therapy were enrolled: Stage 1 included three infusions with prior IgG product followed by 6 months with Subgam, Stage 2 involved long-term Subgam therapy up to 4 years.Stage 1, 85% of the subjects aged >12 years and 93% of the subjects aged <12 years achieved IgG levels ≥6 and ≥4 g/L, respectively at all observations. There were 3.62 infections/patient/year during Subgam treatment. The most common product-related events were infusion site reactions (50% of patients. Recent post-hoc pharmacokinetics analysis of the post-infusion serum total IgG concentration indicated that the mean dose-normalised incremental IgG AUCτ following intravenous dosing (120.5 g.day/L was 1.64-fold that of the dose-normalised mean incremental IgG AUCτ following subcutaneous dosing (73.6 g.day/L, corresponding to an estimated IgG bioavailability for subcutaneous dosing of 61%. Only 34 post-licensing adverse reactions have been received in 30 patients over a period of 10 years; fourteen were classed as serious as defined by the ICH guidelines on good clinical practice. The most common post-licensing adverse reaction was infusion site reaction (7 reports. There were 7 reports of flu-like symptoms (pyrexia/shivering/rigors/feeling hot or cold, 2 other reports of combined flu-like symptoms and infusion site reactions, 5 reports of generalised skin reactions, and 3 reports of combined infusion site and skin reactions. There were also reports of anaphylaxis (2 reports and 8 other adverse events (including headache. In conclusion, Subgam is effective and well tolerated in the treatment of PID.ClinicalTrials.gov NCT02247141.

  18. Safety and persistence of orally administered human Lactobacillus sp. strains in healthy adults.

    Science.gov (United States)

    Hütt, P; Kõll, P; Stsepetova, J; Alvarez, B; Mändar, R; Krogh-Andersen, K; Marcotte, H; Hammarström, L; Mikelsaar, M

    2011-03-01

    The aim of the study was to evaluate the safety and persistence of selected Lactobacillus strains in the gastrointestinal tract (GIT) of healthy adult volunteers after oral consumption of high doses of lactobacilli to identify potential candidates for probiotic and biotechnological applications. In the first phase of the study, nine individuals consumed capsules containing Lactobacillus gasseri 177 and E16B7, Lactobacillus acidophilus 821-3, Lactobacillus paracasei 317 and Lactobacillus fermentum 338-1-1 (each daily dose 1×1010 cfu) for 5 consecutive days. Data on gut health, blood parameters, and liver and kidney function were collected. The persistence of Lactobacillus strains was assessed by culturing combined with arbitrarily primed polymerase chain reaction (AP-PCR) and PCR-denaturing gradient gel electrophoresis (PCR-DGGE) on days 0, 5, 8, 10 and 20 from faecal samples. All strains survived gastrointestinal passage and were detected on the 5th day. L. acidophilus 821-3 was detected in four volunteers on the 8th day (4.3 to 7.0 log10 cfu/g) and in two on the 10th day (8.3 and 3.9 log10 cfu/g, respectively). In the second phase of the study, five additional volunteers consumed L. acidophilus 821-3 (daily 1×1010 cfu) for 5 consecutive days. The strain was subsequently detected in faeces of all individuals using real-time PCR on the 10th day (range 4.6-6.7; median 6.0 log10 cell/g) in both phases of the study for at least 5 days after discontinuation of consumption. The administration of high doses of different Lactobacillus strains did not result in any severe adverse effects in GIT and/or abnormal values of blood indices. Thus, the strain L. acidophilus 821-3 is a promising candidate for probiotic and biotechnological applications. Further studies will be performed to confirm the strain persistence and safety in a larger number of individuals.

  19. Pharmacokinetics and metabolism of an intravenously administered penem (Sch 34343) in humans.

    Science.gov (United States)

    Lin, C C; Lim, J; Radwanski, E; Kim, H K; Marco, A; Lapiguera, A; DiGiore, C; Symchowicz, S

    1987-01-01

    The pharmacokinetics of Sch 34343, a new broad-spectrum penem antibiotic, was studied in subjects receiving 1 g of 14C-labeled drug by intravenous administration. At the end of a 30-min intravenous infusion, the mean maximum concentration of drug in serum was 39 micrograms/ml for unchanged Sch 34343 and 49 mu eq/ml for total radioactivity. The mean serum half-lives of Sch 34343 were 0.16 h for the distribution phase and 0.80 h for the elimination phase. The total body clearance of Sch 34343 was 7.52 ml/min per kg, and the mean apparent volume of distribution was 525 ml/kg. Over a 4-day period, mean urinary excretion of radioactivity accounted for 87.9% of the dose, and mean urinary excretion of unchanged Sch 34343 accounted for 23.6% of the dose. The total radioactivity in feces on days 0 to 6 accounted for only 0.8% of the dose. In serum from 0.5 and 1 h, unchanged Sch 34343 represented the major radioactive peak, with negligible amounts of several metabolites. In urine, there were at least six metabolites in addition to Sch 34343. The amount of unchanged Sch 34343 accounted for 33% of radioactivity in samples of urine from 0 to 2 h, 22% in urine from 2 to 4 h, 15% in urine from 4 to 8 h, and 0% in urine from 8 to 12 h. PMID:3566242

  20. Pharmacokinetics and metabolism of an intravenously administered penem (Sch 34343) in humans

    Energy Technology Data Exchange (ETDEWEB)

    Lin, C.C.; Lim, J.; Radwanski, E.; Kim, H.K.; Marco, A.; Lapiguera, A.; DiGiore, C.; Symchowicz, S.

    1987-01-01

    The pharmacokinetics of Sch 34343, a new broad-spectrum penem antibiotic, was studied in subjects receiving 1 g of /sup 14/C-labeled drug by intravenous administration. At the end of a 30-min intravenous infusion, the mean maximum concentration of drug in serum was 39 micrograms/ml for unchanged Sch 34343 and 49 mu eq/ml for total radioactivity. The mean serum half-lives of Sch 34343 were 0.16 h for the distribution phase and 0.80 h for the elimination phase. The total body clearance of Sch 34343 was 7.52 ml/min per kg, and the mean apparent volume of distribution was 525 ml/kg. Over a 4-day period, mean urinary excretion of radioactivity accounted for 87.9% of the dose, and mean urinary excretion of unchanged Sch 34343 accounted for 23.6% of the dose. The total radioactivity in feces on days 0 to 6 accounted for only 0.8% of the dose. In serum from 0.5 and 1 h, unchanged Sch 34343 represented the major radioactive peak, with negligible amounts of several metabolites. In urine, there were at least six metabolites in addition to Sch 34343. The amount of unchanged Sch 34343 accounted for 33% of radioactivity in samples of urine from 0 to 2 h, 22% in urine from 2 to 4 h, 15% in urine from 4 to 8 h, and 0% in urine from 8 to 12 h.

  1. Pharmacokinetics of Dapsone Administered Daily and Weekly in Human Immunodeficiency Virus-Infected Children

    Science.gov (United States)

    Mirochnick, Mark; Cooper, Ellen; McIntosh, Ken; Xu, Jing; Lindsey, Jane; Jacobus, David; Mofenson, Lynne; Sullivan, John L.; Dankner, Wayne; Frenkel, Lisa M.; Nachman, Sharon; Wara, Diane W.; Johnson, Daniel; Bonagura, Vincent R.; Rathore, Mobeen H.; Cunningham, Coleen K.; McNamara, James

    1999-01-01

    Although dapsone is a commonly used alternative agent for prophylaxis against Pneumocystis carinii pneumonia in children intolerant to trimethoprim-sulfamethoxazole, there are few data that describe dapsone pharmacokinetics in children. We studied dapsone pharmacokinetics in 30 children (median age, 2.8 years; age range, 0.3 to 12 years) receiving a new proprietary liquid preparation by three dosing regimens (1 mg/kg of body weight daily, 2 mg/kg daily, or 4 mg/kg weekly). Dosing of children with 2 mg/kg daily or 4 mg/kg weekly resulted in peak concentrations equivalent to those reached in adults receiving 100-mg tablets daily. For the entire population, the median half-life was 22.2 h (range, 7.1 to 40.3 h), the median oral clearance was 0.0365 liter/kg/h (range, 0.0104 to 0.1021 liter/kg/h), and the median oral apparent volume of distribution was 1.13 liters/kg (range, 0.50 to 2.32 liters/kg). The median dapsone oral clearance was significantly increased in those infants less than 2 years of age compared to the oral clearance in those over 2 years of age (0.0484 versus 0.0278 liter/kg/h; P = 0.011). These data suggest that absorption of this liquid preparation is adequate and that the concentrations in the sera of children receiving 2 mg/kg daily or 4 mg/kg weekly are equivalent to those seen in adults receiving standard dapsone dosing. Dapsone oral clearance appears to be increased in children under 2 years of age. PMID:10543733

  2. 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...

  3. 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... (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION ADULT EDUCATION STATE-ADMINISTERED BASIC GRANT PROGRAM General § 461.1 What is the Adult Education State-administered Basic Grant...

  4. Effects of surface-bound and intravenously administered heparin on cell-surface interactions: inflammation and coagulation.

    Science.gov (United States)

    Johnson, G; Curry, B; Cahalan, L; Prater, R; Biggerstaff, J; Hussain, A; Gartner, M; Cahalan, P

    2013-05-01

    Intravenous administration of heparin and heparin-bonded extracorporeal circuits are frequently used to mitigate the deleterious effects of blood contact with synthetic materials. The work described here utilized human blood in a micro-perfusion circuit to experimentally examine the effects of intravenous and surface-bound heparin on cellular activation. Activation markers of coagulation and of the inflammatory response were examined using flow cytometry; specifically, markers of platelet, monocyte, polymorphonuclear leukocyte (PMN), and lymphocyte activation were quantified. The results indicate that surface-bound heparin reduces the inflammatory response whereas systemically administered heparin does not. This finding has important implications for blood-contacting devices, particularly within the context of recently elucidated connections between inflammation pathways and coagulation disorders. Data presented indicate that surface-bound heparin and intravenously administered heparin play distinct, but vital roles in rendering biomaterial surfaces compatible with blood.

  5. 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.

  6. The safety of high-dose buprenorphine administered subcutaneously in cats.

    Science.gov (United States)

    Sramek, M K; Haas, M C; Coleman, G D; Atterson, P R; Hamlin, R L

    2015-10-01

    The safety of a proprietary formulation of buprenorphine hydrochloride administered subcutaneously (SC) to young cats was investigated in a blinded, randomized study. Four cohorts of eight cats aged approximately 4 months were administered saline, 0.24, 0.72 or 1.20 mg/kg/day buprenorphine SC for nine consecutive days, representing 0×, 1×, 3× and 5× of the intended dose. Cats were monitored daily for evidence of clinical reactions, food and water intake and adverse events (AEs). Physical examinations, clinical pathology, vital signs and electrocardiograms (ECGs) were evaluated at protocol-specified time points. Complete necropsy and histopathologic examinations were performed following humane euthanasia. Four buprenorphine-treated cats experienced AEs during the study, two unrelated and two related to study drug administration. The two cats with AEs considered related to drug administration had clinical signs of hyperactivity, difficulty in handling, disorientation, agitation and dilated pupils in one 0.24 mg/kg/day cat and one 0.72 mg/kg/day cat. All of these clinical signs were observed simultaneously. There were no drug-related effects on survival, injection response, injection site inspections, body weight, food or water consumption, bleeding time, urinalysis, respiration rate, heart rate, ECGs, blood pressures, body temperatures, macroscopic examinations or organ weights. Once daily buprenorphine s.c. injections at doses of 0.24, 0.72 and 1.20 mg/kg/day for 9 consecutive days were well tolerated in young domestic cats. © 2015 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

  7. Adherence to Safe Handling Guidelines by Health Care Workers Who Administer Antineoplastic Drugs

    Science.gov (United States)

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

    2015-01-01

    The toxicity of antineoplastic drugs is well documented. Many are known or suspected human carcinogens where no safe exposure level exists. Authoritative guidelines developed by professional practice organizations and federal agencies for the safe handling of these hazardous drugs have been available for nearly three decades. As a means of evaluating the extent of use of primary prevention practices such as engineering, administrative and work practice controls, personal protective equipment (PPE), and barriers to using PPE, the National Institute for Safety and Health (NIOSH) conducted a web survey of health care workers in 2011. The study population primarily included members of professional practice organizations representing health care occupations which routinely use or come in contact with selected chemical agents. All respondents who indicated that they administered antineoplastic drugs in the past week were eligible to complete a hazard module addressing self-reported health and safety practices on this topic. Most (98%) of the 2069 respondents of this module were nurses. Working primarily in hospitals, outpatient care centers, and physician offices, respondents reported that they had collectively administered over 90 specific antineoplastic drugs in the past week, with carboplatin, cyclophosphamide, and paclitaxel the most common. Examples of activities which increase exposure risk, expressed as percent of respondents, included: failure to wear nonabsorbent gown with closed front and tight cuffs (42%); intravenous (I.V.) tubing primed with antineoplastic drug by respondent (6%) or by pharmacy (12%); potentially contaminated clothing taken home (12%); spill or leak of antineoplastic drug during administration (12%); failure to wear chemotherapy gloves (12%); and lack of hazard awareness training (4%). The most common reason for not wearing gloves or gowns was “skin exposure was minimal”; 4% of respondents, however, reported skin contact during handling

  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. Differences in efficiency, satisfaction and adverse events between self-administered intradermal and nurse-administered intramuscular influenza vaccines in hospital workers.

    Science.gov (United States)

    Coleman, Brenda L; McNeil, Shelly A; Langley, Joanne M; Halperin, Scott A; McGeer, Allison J

    2015-11-27

    Vaccinating healthcare workers against influenza takes tens of thousands of hours of work annually. This study was undertaken to determine the acceptability, success rate, and time to vaccinate healthcare workers in nurse-led groups that self-vaccinated with intradermal influenza vaccine compared with nurse-administered intramuscular vaccine. Volunteer hospital workers were randomly assigned to groups that either self-administered intradermal influenza vaccine (Intanza(®)) in a nurse-led group or received nurse-administered intramuscular vaccine (Vaxigrip(®)). Research assistants timed vaccination procedures; pre- and post-injection questionnaires assessed acceptability and reactogenicity. 810 adults, 21-69 years of age, from two study sites were vaccinated: 401 self-administered the intradermal vaccine while 409 received their intramuscular vaccine from a nurse. Of those who self-administered for the first time, 98.5% were successful on their first attempt with an additional 1.5% on their second attempt. Acceptability was high: 96% were very or somewhat certain that they administered the vaccine correctly, 83% would choose intradermal influenza vaccine again and of those, 75% would choose self-administration again, if given the choice. It took 51.3-72.6s per person for the nurses to guide the groups through the self-administration process, which was significantly less time than it took to individually administer the intramuscular vaccines (93.6s). Self-administration of intradermal influenza vaccine by people working in healthcare settings is a possible alternative to nurse administered vaccinations, with nurse-led group sessions a good way of teaching the technique while being available to respond to unanticipated problems (NCT01665807). Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. 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.

  11. Orally administered lactoferrin restores humoral immune response in immunocompromised mice.

    Science.gov (United States)

    Artym, Jolanta; Zimecki, Michal; Paprocka, Maria; Kruzel, Marian L

    2003-10-09

    Cyclophosphamide (CP) is an anti-tumor drug commonly used in the chemotherapy of human cancer and autoimmune diseases. In our previous studies, we have demonstrated that lactoferrin (LF), given orally to CP-immunosuppressed mice, could reconstitute a T cell mediated immune response by the renewal of the T cell population. The aim of this present study was to evaluate the effects of LF on humoral responses in mice treated with cyclophosphamide. We demonstrate that a single, sublethal dose of cyclophosphamide (400 mg/kg body weight) profoundly inhibited the humoral immune response of CBA mice to sheep red blood cells (SRBC), as measured by the number of antibody forming cells (AFC) in the spleen after 5 weeks following CP treatment. Administration of 0.5% bovine LF in drinking water for 5 weeks partially reconstituted the AFC number (30-40% of the control values, but 7-10x more than in CP-treated controls). Determination of T and B cell levels in the spleens by flow cytometry revealed that the content of CD3+ and CD4+ as well as Ig+ splenocytes was elevated in the immunocompromised mice treated with LF. In addition, the number of peritoneal macrophages was partially restored following LF treatment. Evaluation of the proliferative response to concanavalin A (ConA) and pokeweed mitogen (PWM) demonstrated that the diminished reactivity of splenocytes from CP-treated mice was significantly enhanced by LF. In summary, we conclude that the prolonged, oral treatment of immunocompromised mice with LF led to partial reconstitution of the humoral response, associated with elevation of T and B cell and macrophage content and the proliferative response of splenocytes to mitogens.

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

    Science.gov (United States)

    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 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. PMID:23950972

  13. Toxicokinetics and lack of uterotropic effect of orally administered S-equol.

    Science.gov (United States)

    Schwen, Richard J; Nguyen, Linh; Plomley, Jeffrey B; Jackson, Richard L

    2012-05-01

    S-equol is a natural product that is produced by the microbial biotransformation of daidzein, an isoflavone found in soy. Evidence suggests that the health benefits of soy may be related to one's ability to produce S-equol, thus S-equol is being developed for the treatment of vasomotor symptoms in postmenopausal women. The toxicokinetics of S-equol were evaluated in Sprague-Dawley rats and cynomolgus monkeys; S-equol was rapidly absorbed with C(max) occurring between 0.5 h and 1.0 h in the rat and 3h in the monkey. AUC was linear over the doses tested with no differences between male and female animals. Conjugated S-equol was the major metabolite in plasma with less than 1% present as the unconjugated form. S-equol showed a weak induction of liver cytochrome P450s in vivo, and did not significantly inhibit the major human cytochrome P450s in vitro. S-equol was highly protein bound (>95%) in rat, monkey and man in a concentration-independent manner. Orally administered S-equol did not significantly change uterine weight or morphology in either the rat or monkey even at the highest doses tested. These studies show that S-equol has pharmacokinetic parameters suitable for drug development with a low potential for uterotropic effects. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. The effect of parenterally administered cyclodextrins on the pharmacokinetics of coadministered drugs.

    Science.gov (United States)

    Kurkov, Sergey V; Madden, Donna E; Carr, Daniel; Loftsson, Thorsteinn

    2012-12-01

    Cyclodextrins are used increasingly to formulate otherwise poorly soluble molecules for clinical use. Cyclodextrins, such as 2-hydroxypropyl-β-cyclodextrin (HPβCD) and sulfobutylether β-cyclodextrin (SBEβCD), are found in marketed parenteral drug formulations. Depending upon the relative affinities of a coadministered medication for cyclodextrin and plasma proteins, complexation with HPβCD or SBEβCD may alter its pharmacokinetics (PK). To explore this possibility, we applied a previously developed model for competitive binding of drugs with HPβCD and human serum albumin to a variety of commonly administered medications. We modeled this potential interaction in medications chosen on the basis of a hypothetical detrimental effect of HPβCD complexation with their therapeutic action (e.g., antibiotics), supplemented by a composite listing of concurrent medications. Stability constant (K(1:1)) values for drug-HPβCD 1:1 inclusion complexes were extracted from our own data and the literature. The K(1:1) values for the drugs tested ranged from 2 to 40,000 M(-1) and the plasma protein binding from about 20% to over 99%. None of the 63 drugs examined in the present study had a sufficiently high K(1:1) value for HPβCD complexation to affect plasma protein binding to a degree that would be expected to alter their PK substantively, for example, to require increased doses. Copyright © 2012 Wiley Periodicals, Inc.

  15. Evaluation of ATC as an Orally Administered Drug in Treatment of Cadmium Toxicity of Rat Organs

    Directory of Open Access Journals (Sweden)

    S. Nabilaldine Fatemi

    2009-01-01

    Full Text Available The effect of N-tetramethylene dithiocarbamate (ATC as a chelating agent on the excretion of cadmium was evaluated in cadmium-poisoned Wistar rats following administration through food and drink. The present research aimed to characterize the potential efficiency of ATC as an orally administered chelator drug after cadmium administration for 60 days. This chelator significantly enhanced the urinary and biliary excretion of cadmium and restored the altered levels of iron. Cadmium and iron concentrations in different tissues were determined by graphite furnace and flame atomic absorption spectrometry (GF AAS and F AAS methods, respectively. The chelation therapy results show that ATC is able to remove cadmium ions from different tissues while iron concentration returned to the normal level and the clinical symptoms were also reduced. In summary, we conclude that ATC is able to mobilize and promote the excretion of cadmium in rat organs and reduce the side effects and general symptoms of toxicity caused by cadmium and might be useful for preliminary testing of the efficacy of chelating agents in human body. However, these results should be confirmed in different experimental models before extrapolation to other systems. This testing procedure of course does not provide all the relevant answers for evaluating the efficiency of chelating agents in cadmium toxicity.

  16. Comparison of the analgesic properties of transdermally administered fentanyl and intramuscularly administered buprenorphine during and following experimental orthopedic surgery in sheep.

    Science.gov (United States)

    Ahern, Benjamin J; Soma, Lawrance R; Boston, Raymond C; Schaer, Thomas P

    2009-03-01

    To evaluate the analgesic properties of transdermally administered fentanyl and IM administered buprenorphine in sheep undergoing unilateral tibial osteotomy. 20 mature sheep. Fentanyl patches (n = 15 sheep) or placebo patches (5 sheep) were applied 12 hours before sheep underwent general anesthesia and a unilateral tibial osteotomy. Buprenorphine was administered to the placebo group every 6 hours commencing at time of induction. Signs of pain were assessed every 12 hours after surgery by 2 independent observers unaware of treatment groups. There were no differences in preoperative and intraoperative physiologic data between the 2 groups. Sheep treated with fentanyl required less preoperative administration of diazepam for sedation and had significantly lower postoperative pain scores, compared with those treated with buprenorphine. No complications associated with the antebrachium at the site of patch application were detected. Under the conditions of this study, transdermally administered fentanyl was a superior option to IM administered buprenorphine for alleviation of postoperative orthopedic pain in sheep. This information can be used to assist clinicians in the development of a rational analgesic regimen for research and clinical patients.

  17. 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

  18. 40 CFR 147.1401 - State administered program-Class I, III, IV and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Nebraska § 147.1401 State administered program—Class I, III, IV and V wells. The UIC program for Class I, III, IV, and V wells in the State of Nebraska, except those on Indian lands, is the... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State administered program-Class I...

  19. 77 FR 19425 - Prescription Drugs Not Administered During Treatment; Update to Administrative Cost for Calendar...

    Science.gov (United States)

    2012-03-30

    ... AFFAIRS Prescription Drugs Not Administered During Treatment; Update to Administrative Cost for Calendar... purposes of calculating VA's charges for prescription drugs that were not administered during treatment but....101 of title 38, Code of Federal Regulations, sets forth VA's medical regulations concerning the...

  20. 34 CFR 406.1 - What is the State-Administered Tech-Prep Education Program?

    Science.gov (United States)

    2010-07-01

    ... Program? 406.1 Section 406.1 Education Regulations of the Offices of the Department of Education... EDUCATION PROGRAM General § 406.1 What is the State-Administered Tech-Prep Education Program? If the annual appropriation for tech-prep education exceeds $50,000,000, the State-Administered Tech-Prep Education Program...

  1. Efficacy of rSEB Vaccine and CpG ODN Administered by Inhalation in Monkeys

    Science.gov (United States)

    2003-11-19

    aerosol challenge using either rSEB alone, CpG ODN alone, or comixed administered either by injection, inhalation, or combination of routes thereof...using either rSEB alone, CpG ODN alone, or comixed administered either by injection, inhalation, or combination of routes thereof. P R O J E C

  2. 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"....

  3. Advanced Life Support Providers Have Poor Knowledge of When to Administer Resuscitation Drugs

    DEFF Research Database (Denmark)

    Johnsen, Josephine; Glerup Lauridsen, Kasper; Løfgren, Bo

    2017-01-01

    Background: Advanced life support (ALS) including resuscitation drugs improves return of spontaneous circulation after cardiac arrest. Resuscitation drugs are recommended to be administered at predefined time-points depending on whether the cardiac rhythm is shockable or non-shockable. Timing...... to administer drugs during shockable rhythm only. Similar, only one third knew when to administer drugs during non-shockable rhythm only. Knowledge on when to administer drugs in case of rhythm transition was poor (Figure 1).Conclusion: Advanced life support providers have poor knowledge of when to administer...... resuscitation drugs. Future studies should address methods to improve learning and skill retention of resuscitation drug administration.Author Disclosures: J. Johnsen: None. K.G. Lauridsen: None. B. Løfgren: None....

  4. Possible therapeutic effect of orally administered ribavirin for respiratory syncytial virus-induced acute respiratory distress syndrome in an immunocompetent patient: a case report.

    Science.gov (United States)

    Yoon, Byung Woo; Lee, Seung Hyeun

    2017-12-20

    Human respiratory syncytial virus usually causes self-limiting upper respiratory infection and occasionally causes pneumonia in immunocompromised hosts. Respiratory syncytial virus-induced severe pneumonia or acute respiratory distress syndrome in immunocompetent adults has been rarely described. Unfortunately, optimal treatment has not been established for this potentially fatal condition. We report a case of respiratory syncytial virus-induced acute respiratory distress syndrome occurring in a previously healthy man successfully treated with orally administered ribavirin. An 81-year-old previously healthy Korean man presented with cough, dyspnea, and febrile sensation. He had hypoxemia with diffuse ground glass opacity evident on chest radiography, which progressed and required mechanical ventilation. All microbiological tests were negative except multiplex real-time reverse transcriptase polymerase chain reaction using respiratory specimen, which was positive for human adenovirus. Under the diagnosis of respiratory syncytial virus-induced acute respiratory distress syndrome, orally administered ribavirin was administered and he recuperated completely without complications. This case demonstrates the potential usefulness of orally administered ribavirin as a therapeutic option for severe respiratory syncytial virus infection, at least in an immunocompetent host.

  5. Effects of orally self-administered bath salt constituent 3,4-methylenedioxypyrovalerone (MDPV) in mice.

    Science.gov (United States)

    Gannon, Brenda M; Russell, Lauren N; Modi, Meet S; Rice, Kenner C; Fantegrossi, William E

    2017-10-01

    Synthetic cathinones in bath salts products are psychostimulant drugs of abuse, and 3,4-methylenedioxypyrovalerone (MDPV) is a common constituent of these products. Oral MDPV has been show to stimulate locomotor activity but reinforcing, locomotor and appetitive stimulus effects of oral MDPV are unknown. Choice procedures evaluated preference for 0.03, 0.10, 0.30, and 1.00mg/mL MDPV solutions versus 0.10mg/mL quinine solution or water. To verify that oral MDPV produced pharmacological effects, locomotor activity was monitored during and after consumption of water, quinine, or MDPV solutions. Conditioned place preference (CPP) tested the apparent appetitive effects of a preferred concentration of oral MDPV with locomotor stimulant effects (0.30mg/mL), using water as a control, and compared with results from intraperitoneally-administered MDPV. Consumption of MDPV solutions (0.03-1.00mg/mL) was low when the alternative fluid was water, but a history of MDPV consumption increased MDPV choice. When paired with a quinine control solution, MDPV solutions (0.03-0.30mg/mL) were almost exclusively preferred, and treatment with the catecholamine synthesis inhibitor αMPT decreased MDPV choice. Consumption of MDPV concentrations (0.1-1.0mg/mL) stimulated locomotor activity. Chronic (10day) access to 0.30mg/mL MDPV resulted in escalated consumption, but locomotor effects did not systematically change across the access period. Finally, consumption of 0.30mg/mL MDPV elicited CPP with a magnitude similar to the preference observed following intraperitoneal administration of MDPV. Consistent with human abuse patterns, oral MDPV has reinforcing effects in the mouse which are most likely related to its psychostimulant-like pharmacological profile. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. 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......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 intraspinal release of acetylcholine. In the present study it was hypothesized that systemically administered lidocaine is acting through the same mechanisms as cholinergic agonists and affects the intraspinal release of acetylcholine. Microdialysis probes were placed in anesthetized rats for sampling...... of acetylcholine. Ten and 30 mg/kg lidocaine injected intravenously significantly increased the intraspinal release of acetylcholine. The effect of lidocaine could be reduced by pretreatment with intraspinally administered atropine or mecamylamine. Our results suggest that the antinociceptive effect produced...

  7. 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).

  8. Initial validation of a computer-administered Addiction Severity Index: the ASI-MV.

    Science.gov (United States)

    Butler, S F; Budman, S H; Goldman, R J; Newman, F L; Beckley, K E; Trottier, D; Cacciola, J S

    2001-03-01

    The Addiction Severity Index--Multimedia Version (ASI-MV) is a CD-ROM-based simulation of the interviewer-administered Addiction Severity Index (ASI). Clients in treatment (N = 202) self-administered the ASI-MV to examine the test-retest reliability, criterion validity, and convergent-discriminant validity of the ASI-MV. Excellent test-retest reliability was observed for composite scores and severity ratings. Criterion validity, tested against the interviewer-administered ASI, was good for the composite scores. For severity ratings, variable agreement was observed between the ASI-MV and each interviewer, suggesting poor interrater reliability among interviewers. This conclusion was bolstered by a finding of superior convergent-discriminant validity for both composite scores and severity ratings compared to the standard ASI. The ASI-MV is a viable alternative to the expensive and potentially unreliable interviewer-administered version.

  9. The effectiveness of self-administered treatments: a practice-friendly review of the research.

    Science.gov (United States)

    Mains, Jennifer A; Scogin, Forrest R

    2003-02-01

    Self-administered treatments are a cost-effective way to treat a broad spectrum of people. This article focuses on the existing research of self-administered treatments and their effectiveness when integrated with ongoing practice or when implemented alone. Evidence for their effectiveness is mixed; self-help has been proven successful in the treatment of depression, mild alcohol abuse, and anxiety disorders. It has proven less successful for smoking cessation and moderate to severe alcohol abuse. When determining whether self-administered treatment is appropriate, individual characteristics and attitude as well as the nature and severity of the problem should be taken into consideration. In addition, because many self-help treatments have not been evaluated, caution should be exercised when implementing self-administered treatment, and progress should be carefully monitored. Copyright 2003 Wiley Periodicals, Inc.

  10. Historical review of the use of motorized vehicles on lands administered by Izembek Refuge

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The purpose of this report is to review and describe the historical use of motorized vehicles within lands administered by the Izembek National Wildlife Refuge, with...

  11. Distribution pattern of cholinesterase enzymes in human tooth germs.

    Science.gov (United States)

    Nandasena, T L; Jayawardena, C K; Tilakaratne, W M; Nanayakkara, C D

    2010-08-01

    The two distinct molecular forms of cholinesterase (ChE) are acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Our previous studies have reported that ChE is involved in tooth development. However, further experiments are needed to understand the precise action of ChE in tooth development. This study aimed to localise types of ChE in human tooth germs, and identify their distribution pattern. ChE were localised in frozen sections of jaws which were prepared from dead fetuses, neonates and stillborns who were free from visible abnormalities by Karnovsky and Root method. AChE was identified in the inner and outer enamel epithelia including the cervical loop region, stratum intermedium and preameloblasts of tooth germs at bell stage. Secretory ameloblasts were free from staining. The bud and cap stages of permanent tooth germs showed AChE activity on the lingual aspect and top surface of the epithelial ingrowths, respectively. BuChE activity was localised in the degenerating dental lamina. Our study reported the first evidence of localisation of ChE in human tooth development and identified the possible molecular form of ChE in tooth germs as AChE. Also, our results have provided strong evidence to speculate the action of AChE is on the cells of enamel organ during tooth development.

  12. 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 i...... 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....

  13. Evaluation of administered dose using portal images in craniospinal irradiation of pediatric patients.

    Science.gov (United States)

    Coelho, Carina Marques; Calçada, Raquel; Rodrigues, Sofia; Barragán, Juan Antonio; Sá, Ana Cravo; Macedo, Ana Paula; de Fátima Monsanto, Maria

    2017-09-01

    This study aimed to assess the administered dose based on portal imaging in craniospinal pediatric irradiation by evaluating cases in which portal images did or did not account for the total administered dose. We also intended to calculate the mean increase in total administered dose. Data were collected from General University Hospital Gregorio Marañón; we evaluated the total dose administered, total dose planned, number of portal images per treatment and corresponding monitor units of two different groups: one in which the dose from portal images is deducted from the total administered dose (D), and another in which it was not (N). We used descriptive statistics to analyze the collected data, including the mean and respective standard deviation. We used the Shapiro-Wilk and Spearman rank correlation coefficient tests and estimated the linear regression coefficients. Patients in group D received a mean dose of 29.00 ± 10.28 cGy based on the verification portal images, a quantity that was deducted from the planned dose to match the total administered dose. Patients in group N received a mean dose of 41.50 ± 30.53 cGy, which was not deducted from the planned dose, evidencing a mean increase of 41.50 ± 30.55 cGy over the total administered dose. The acquisition of the set-up verification portal images, without their inclusion in the total administered dose, reflects an average increase in total dose for craniospinal irradiation of pediatric patients. Subtraction of the monitor units used to acquire the verification images is recommended.

  14. 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....

  15. How to set up and administer an enteral feed via a nasogastric tube.

    Science.gov (United States)

    Best, Carolyn

    2017-07-05

    Rationale and key points Nasogastric tube feeding is a method of enteral feeding commonly administered by nurses. Feed can be administered either using a volumetric enteral feeding pump (pump feeding) or via an enteral syringe (bolus feeding). This article explains how nurses can safely undertake these two methods of nasogastric tube feed administration at the patient's bedside. » Nasogastric tube feeding can be used to provide some or all of the patient's nutrition, fluid or medication. » Nurses should be equipped with the relevant knowledge to flush a nasogastric tube before the administration of feed or medication; set up and administer an enteral feed via a volumetric enteral feeding pump; and set up and administer a feed using a bolus method. » The position of the distal tip of the nasogastric tube must be confirmed as sitting in the patient's stomach before the tube is used to administer enteral feed, fluid or medication. Reflective activity 'How to' articles can help you update your practice and ensure it remains evidence-based. Apply this article to your practice. Reflect on and write a short account of: 1. How you think this article will change your practice when setting up and administering an enteral feed via a nasogastric tube. 2. How you could use this resource to educate your colleagues about nasogastric tube feeding via an enteral feeding pump or bolus feeding.

  16. Influence of time at which oxytocin is administered during labor on uterine activity and perinatal death in pigs

    Directory of Open Access Journals (Sweden)

    DANIEL MOTA-ROJAS

    2007-01-01

    Full Text Available Oxytocin is extensively used to induce or augment uterine contractions, especially to facilitate the third stage of labor in humans. Administration of oxytocin to parturient sows reduces duration of labor whereas mortality of the offspring may remain unchanged. This study aimed to evaluate whether time of administration of oxytocin during parturition may alter the uterine response and fetal outcomes. Two hundred parturient sows were randomly assigned to intramuscularly receive either saline solution (control group or oxytocin 0.083 IU/kg immediately after the delivery of the 1st, 4th or 8th piglet (groups O-1, 0-4 and 0-8, respectively. Uterine effects and fetal outcomes were registered in all groups. The duration of labor was 20-40 min shorter (P < 0.0001 and time interval between babies was reduced by 3-5 min (P < 0.0001 in the three groups receiving oxytocin. The duration and intensity of contractions, meconium-stained piglets and intrapartum deaths decreased as time at which oxytocin administered during labor was increased. In group 0-8, we observed approximately 70% less meconium-stained piglets and intrapartum deaths than in the control group. In conclusion, oxytocin administered at early phases of parturition to sows may increase duration and intensity of uterine contractions as well as adverse fetal outcomes

  17. 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

  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. Effect of bismuth salts on systemic and mucosal immune responses to orally administered cholera toxin.

    Science.gov (United States)

    Horowitz, N S; Staats, H F; Palker, T J

    1995-11-01

    While the antimicrobial and antisecretory effects of bismuth salts are well documented, little is known regarding their effects on immune responses to enterotoxins such as that of V. cholerae or to orally administered vaccine antigens. To evaluate the effects of Pepto Bismol (PB) on the induction of systemic and mucosal immune responses to cholera toxin (CT), C57BL/6 mice were orally administered 10 micrograms CT and PB, or mice were pretreated with PB 30 min prior to CT administration. When co-administered with CT, PB attenuated serum IgG1, IgG2a, IgG2b and IgG3 anti-CT responses in a dose-dependent manner and also reduced levels of circulating anti-CT IgA and total serum IgE. Similarly, anti-CT intestinal IgA responses were also decreased. However, when administered 30 min prior to CT, PB had little to no effect on serum or intestinal anti-CT immunoglobulin responses. Administration of bismuth subsalicylate (BSS), the active component of PB, or sodium salicylate did not reduce immune responses to CT, suggesting that the combination of BSS plus other constituents contained within PB contributed to the decreased immune response to CT. Moreover, bismuth subgallate alone inhibited antibody responses to CT. Our data are consistent with the hypothesis that, when administered orally with CT, PB and bismuth subgallate create a physical barrier to antigen uptake.

  20. Comparative Discussion on Psychophysiological Effect of Self-administered Facial Massage by Treatment Method

    Science.gov (United States)

    Nozawa, Akio; Takei, Yuya

    The aim of study was to quantitatively evaluate the effects of self-administered facial massage, which was done by hand or facial roller. In this study, the psychophysiological effects of facial massage were evaluated. The central nerves system and the autonomic nervous system were administered to evaluate physiological system. The central nerves system was assessed by Electroencephalogram (EEG). The autonomic nervous system were assessed by peripheral skin temperature(PST) and heart rate variability (HRV) with spectral analysis. In the spectral analysis of HRV, the high-frequency components (HF) were evaluated. State-Trait Anxiety Inventory (STAI), Profile of Mood Status (POMS) and subjective sensory amount with Visual Analog Scale (VAS) were administered to evaluate psychological status. These results suggest that kept brain activity and had strong effects on stress alleviation.

  1. 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.

  2. 75 FR 7440 - Oil and Gas Leasing on Lands Administered by the Dixie National Forest, Supplemental Information...

    Science.gov (United States)

    2010-02-19

    ... report to the Oil and Gas Leasing on Lands Administered by the Dixie National Forest Final Environmental... Forest Service Oil and Gas Leasing on Lands Administered by the Dixie National Forest, Supplemental... considered, the FS must receive written comments on the Oil and Gas Leasing on Lands Administered by the...

  3. 40 CFR 147.2250 - State-administered program-Class I, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Utah § 147.2250 State-administered program—Class I, III, IV, and V wells. The UIC program for Class I, III, IV, and V wells in the State of Utah, except those on Indian lands, is administered... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I...

  4. 34 CFR 692.80 - How does a State administer its community service work-study program?

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false How does a State administer its community service work... Its Community Service Work-Study Program? § 692.80 How does a State administer its community service work-study program? When administering its community service work-study program, a State must follow...

  5. 34 CFR 692.30 - How does a State administer its community service-learning job program?

    Science.gov (United States)

    2010-07-01

    ... Administer Its Community Service-Learning Job Program? § 692.30 How does a State administer its community... community service-learning job program that satisfies the conditions set forth in paragraph (b) of this... not a grant. (b)(1) The community service-learning job program must be administered by institutions in...

  6. Preliminary Reliability and Validity of the Clinician-Administered PTSD Scale for Schizophrenia

    Science.gov (United States)

    Gearon, Jean S.; Bellack, Alan S.; Tenhula, Wendy N.

    2004-01-01

    This study provides preliminary psychometric support for a version of the Clinician-Administered Posttraumatic Stress Disorder (PTSD) Scale (CAPS; D. D. Blake et al., 1990) adapted for use with patients with schizophrenia (CAPS-S; J. S. Gearon. S. Thomas-Lohrman, & A. S. Bellack, 2001). Nineteen women with schizophrenia and co-occurring illicit…

  7. 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)

  8. 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

  9. 40 CFR 147.1400 - State-administered program-Class II wells.

    Science.gov (United States)

    2010-07-01

    ... State of Nebraska, except those on Indian lands, is the program administered by the Nebraska Oil and Gas..., 1984. (1) Rules and Regulations of the Nebraska Oil and Gas Conservation Commission, Rules 1 through 6...-906 (Reissue 1988). (b) Other laws. The following statutes and regulations, although not incorporated...

  10. Employing Computer-Administered Exams in General Psychology: Student Anxiety and Expectations

    Science.gov (United States)

    Schult, Carolyn A.; McIntosh, John L.

    2004-01-01

    Computer-administered exams offer many advantages, but instructors may be reluctant to use them due to concerns that computer anxiety may increase student test anxiety. Introductory psychology students (N = 265) completed surveys prior to their first exam about their anxiety related to the upcoming exam, computers in general, and taking exams on…

  11. 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,…

  12. Quality Control for Scoring Tests Administered in Continuous Mode: An NCME Instructional Module

    Science.gov (United States)

    Allalouf, Avi; Gutentag, Tony; Baumer, Michal

    2017-01-01

    Quality control (QC) in testing is paramount. QC procedures for tests can be divided into two types. The first type, one that has been well researched, is QC for tests administered to large population groups on few administration dates using a small set of test forms (e.g., large-scale assessment). The second type is QC for tests, usually…

  13. 40 CFR 147.50 - State-administered program-Class II wells.

    Science.gov (United States)

    2010-07-01

    ... (Cumm. Supp. 1989); (2) State Oil and Gas Board of Alabama Administrative Code, Oil and Gas Report 1 (supplemented through May 1989), Rules and Regulations Governing the Conservation of Oil and Gas in Alabama, and... Alabama, except those on Indian lands, is the program administered by the State Oil and Gas Board of...

  14. “Aju Mbaise”decoction: A liquid extract administered to nursing ...

    African Journals Online (AJOL)

    Antibacterial activity, phytochemical properties and mineral Content of “Aju Mbaise”decoction: A liquid extract administered to nursing mothers. ... Results: The decoction inhibited the growth of Gram negative bacteria used in the study with maximum inhibition observed against E. coli (9.5mm). The Gram positive bacterium, ...

  15. 40 CFR 147.353 - EPA-administered program-Indian lands.

    Science.gov (United States)

    2010-07-01

    ... requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of this subpart. Injection well owners and operators, and EPA shall comply with these requirements. (b... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Connecticut...

  16. 40 CFR 147.651 - EPA-administered program-Indian lands.

    Science.gov (United States)

    2010-07-01

    ... requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of this subpart. Injection well owners and operators, and EPA shall comply with these requirements. (b... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Idaho § 147...

  17. 40 CFR 147.951 - EPA-administered program-Indian lands.

    Science.gov (United States)

    2010-07-01

    ... program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of this subpart. Injection well owners and operators, and EPA shall comply with these requirements... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Louisiana...

  18. 40 CFR 147.1053 - EPA-administered program-Indian lands.

    Science.gov (United States)

    2010-07-01

    ... program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of this subpart. Injection well owners and operators, and EPA shall comply with these requirements... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Maryland...

  19. 40 CFR 147.205 - EPA-administered program-Indian lands.

    Science.gov (United States)

    2010-07-01

    ... requirements of 40 CFR parts 124, 144, 146, 148 and any additional requirements set forth in this subpart. Injection well owners and operators, and EPA shall comply with these requirements. (b) Effective date. The... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Arkansas...

  20. 40 CFR 147.501 - EPA-administered program-Class II wells and Indian lands.

    Science.gov (United States)

    2010-07-01

    ... 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of this... wells and Indian lands. 147.501 Section 147.501 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION...

  1. 40 CFR 147.553 - EPA-administered program-Indian lands.

    Science.gov (United States)

    2010-07-01

    ... program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of this subpart. Injection well owners and operators, and EPA shall comply with these requirements... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Georgia...

  2. 40 CFR 147.1101 - EPA-administered program-Indian lands.

    Science.gov (United States)

    2010-07-01

    ... UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of this subpart. Injection well owners and operators, and EPA shall comply with... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS...

  3. 40 CFR 147.2404 - EPA-administered program-Colville Reservation.

    Science.gov (United States)

    2010-07-01

    ... CFR part 124, 144 and 146 and any additional requirements set forth in the remainder of this subpart...) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS... Indian Reservation consists of a prohibition of all Class I, II, III and IV injection wells and of a...

  4. 40 CFR 147.403 - EPA-administered program-Indian lands.

    Science.gov (United States)

    2010-07-01

    ... requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of this subpart. Injection well owners and operators and EPA shall comply with these requirements. (b... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Delaware...

  5. 40 CFR 147.1001 - EPA-administered program-Indian lands.

    Science.gov (United States)

    2010-07-01

    ... requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of this subpart. Injection well owners and operators and EPA shall comply with these requirements. (b... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Maine § 147...

  6. 40 CFR 147.60 - EPA-administered program-Indian lands.

    Science.gov (United States)

    2010-07-01

    ... requirements of 40 CFR parts 124, 144, 146, 148 and any additional requirements set forth in the remainder of this subpart. Injection well owners and operators, and EPA shall comply with these requirements. (b... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Alabama...

  7. 40 CFR 147.703 - EPA-administered program-Indian lands.

    Science.gov (United States)

    2010-07-01

    ... program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of this subpart. Injection well owners and operators, and EPA shall comply with these requirements... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Illinois...

  8. 40 CFR 147.860 - EPA-administered program-Indian lands.

    Science.gov (United States)

    2010-07-01

    ... program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of this subpart. Injection well owners and operators, and EPA shall comply with these requirements... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Kansas...

  9. 76 FR 20699 - Fellowship Placement Pilot Program Requests for Expressions of Interest To Administer Pilot

    Science.gov (United States)

    2011-04-13

    ... local organization with relevant experience; or A volunteer or community driven organization and college... activities affecting housing and urban development'' as well as to ``provide technical assistance and... responsible for two major activities of the fellowship program: 1. Manage and administer the fellowship...

  10. 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…

  11. [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.

  12. Postoperative analgesic effects of intravenous, intramuscular, subcutaneous or oral transmucosal buprenorphine administered to cats undergoing ovariohysterectomy.

    Science.gov (United States)

    Giordano, Tatiana; Steagall, Paulo V M; Ferreira, Tatiana H; Minto, Bruno W; de Sá Lorena, Sílvia Elaine Rodolfo; Brondani, Juliana; Luna, Stelio P L

    2010-07-01

    To compare the postoperative analgesic effects of intravenous (IV), intramuscular (IM), subcutaneous (SC) or oral transmucosal (OTM) buprenorphine administered to cats undergoing ovariohysterectomy. Randomized, prospective and blinded clinical trial. 100 female cats. Cats were assigned to receive 0.01 mg kg(-1) of buprenorphine administered by the IV, IM, SC or OTM route (n = 25/group). Buprenorphine was made up to 0.3 mL with 0.9% saline. DIVAS (0-100 mm) and simple descriptive scale (SDS) (from 0 to 4) pain and sedation scores were assigned to each cat before and 1, 2, 3, 4, 6, 8, 12 and 24 hours after ovariohysterectomy. Buprenorphine and carprofen were administered for rescue analgesia. Data were analyzed using anova and Fisher's exact test (p 0.05). There were no significant differences between groups for sedation scores at any time. SDS pain scores did not detect any differences between groups (p > 0.05). DIVAS pain scores after OTM administration were significantly higher than IV and IM administration at 1 hour and at 3, 4, 6, 8 and 12 hours, respectively (p buprenorphine required rescue analgesia, respectively. There was a significantly higher incidence of treatment failure in cats that received SC and OTM buprenorphine compared with cats that received IV and IM buprenorphine (p buprenorphine provided better postoperative analgesia than SC or OTM administration of the drug and these routes of administration should be preferred when buprenorphine is administered to cats.

  13. 21 CFR 1306.07 - Administering or dispensing of narcotic drugs.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Administering or dispensing of narcotic drugs. 1306.07 Section 1306.07 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE... (including prescribe) any Schedule III, IV, or V narcotic drug approved by the Food and Drug Administration...

  14. 31 CFR 363.2 - What agency administers TreasuryDirect ®?

    Science.gov (United States)

    2010-07-01

    ... (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC DEBT REGULATIONS GOVERNING... Public Debt (Public Debt), Department of the Treasury (Treasury) is responsible for administering TreasuryDirect. Public Debt may delegate authority to process certain transactions in TreasuryDirect to...

  15. Depression in People with Intellectual Disability: An Evaluation of a Staff-Administered Treatment Program

    Science.gov (United States)

    McGillivray, Jane A.; McCabe, Marita P.; Kershaw, Mavis M.

    2008-01-01

    The prevalence of co-morbid depression in people with intellectual disability (ID) provides a strong rationale for the early identification and treatment of individuals at risk. The aim of this study was to evaluate a staff-administered group CBT program for the treatment of depression in people with mild ID. A sample of 13 staff employed at two…

  16. Telephone-Administered Cognitive Behavioral Therapy for Veterans Served by Community-Based Outpatient Clinics

    Science.gov (United States)

    Mohr, David C.; Carmody, Timothy; Erickson, Lauren; Jin, Ling; Leader, Julie

    2011-01-01

    Objective: Multiple trials have found telephone-administered cognitive behavioral therapy (T-CBT) to be effective for the treatment of depression. The aim of this study was to evaluate T-CBT for the treatment of depression among veterans served by community-based outpatient clinics (CBOCs) outside of major urban areas. Method: Eighty-five veterans…

  17. 41 CFR 302-14.100 - How should we administer our home marketing incentive payment program?

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 4 2010-07-01 2010-07-01 false How should we administer our home marketing incentive payment program? 302-14.100 Section 302-14.100 Public Contracts and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES RESIDENCE TRANSACTION ALLOWANCES...

  18. Validation of a self-administered FFQ in adults in Argentina, Chile and Uruguay

    National Research Council Canada - National Science Library

    Elorriaga, Natalia; Irazola, Vilma E; Defagó, María D; Britz, Mónica; Martínez-Oakley, Solange P; Witriw, Alicia M; Rubinstein, Adolfo L

    2015-01-01

    ... (Argentina, Chile and Uruguay) of a self-administered FFQ to be used in the CESCAS I Study, an ongoing observational prospective cohort study to detect and follow up CVD and their risk factors, as well as in other epidemiological studies...

  19. 40 CFR 272.201 - Arkansas State-administered program: Final authorization.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Arkansas State-administered program: Final authorization. 272.201 Section 272.201 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY...-7-308(4). (iii) Arkansas Department of Pollution Control and Ecology (ADPC&E) Regulation No. 23...

  20. 9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Disposition of animals administered experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND... PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL...

  1. 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

  2. 22 CFR 196.2 - How is the Fellowship Program administered?

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false How is the Fellowship Program administered? 196.2 Section 196.2 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL COMMERCIAL ARBITRATION THOMAS R. PICKERING FOREIGN AFFAIRS/GRADUATE FOREIGN AFFAIRS FELLOWSHIP PROGRAM § 196.2 How is the Fellowship Program...

  3. 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

  4. 20 CFR 669.120 - How do we administer the NFJP program?

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false How do we administer the NFJP program? 669.120 Section 669.120 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR NATIONAL FARMWORKER JOBS PROGRAM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT Purpose and Definitions...

  5. 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

  6. Injectable dexamethasone sodium phosphate administered orally? A pharmacokinetic analysis of a common emergency department practice.

    Science.gov (United States)

    Toledo, Alexander; Amato, Christopher S; Clarke, Nigel; Reitz, Richard E; Salo, David

    2015-01-01

    The injectable formulation of dexamethasone has been administered orally, for the treatment of pediatric asthma and croup. The practice is followed in emergency departments around the country, but pharmacokinetic data supporting this practice are lacking. This study evaluated the relative bioavailability and pharmacokinetics of dexamethasone sodium phosphate for injection (DSPI) administered orally compared to dexamethasone oral concentrate (DOC) in healthy adults. This was an open label, crossover study of 11 healthy adults 18 to 45 years of age. All subjects received 8 mg of dexamethasone oral concentrate initially. After a 1-week wash-out period, subjects received 8 mg of DSPI administered orally. Dexamethasone levels were measured by liquid chromatography in tandem mass spectrometry. Cmax and area under the curve (AUC (0-t) and AUC (0-∞)) were calculated and compared between groups using the paired t test. The mean ± SD AUC(0-t) for dexamethasone oral concentrate and DSPI were 5497.23 ± 1649 and 4807.82 ± 1971) ng/dL/hr, respectively; 90% confidence interval (CI) was 78.8%-96.9%. The mean ± SD AUC(0-∞) for dexamethasone oral concentrate and DSPI were 6136.43 ± 2577 and 5591.48 ± 3075 ng/dL/hr, respectively; 90% CI was 79.0% -105.2%. Mean Cmax ± SD for DOC and DSPI were 942.94 ± 151 and 790.92 ± 229 ng/dL, respectively; 90% CI 76.8%-91.7%. The relative bioavailability of DSPI administered orally was 87.4% when using AUC(0-t) and 91.1% when using AUC(0-∞). The calculated absolute bioavailability was 75.9%. DSPI is not bioequivalent to dexamethasone oral concentrate when administered orally. The existing literature supports the efficacy of DSPI despite this. Dosing adjustments may be considered.

  7. Buccally Administered Intranasal Desmopressin Acetate for the Treatment of Neurogenic Diabetes Insipidus in Infancy.

    Science.gov (United States)

    Smego, Allison R; Backeljauw, Philippe; Gutmark-Little, Iris

    2016-05-01

    The treatment of neurogenic diabetes insipidus (DI) in infancy is challenging and complicated by fluid overload and dehydration. Therapy with subcutaneous (SC), intranasal (IN), or oral tablet desmopressin acetate (1-desamino-8-D-arginine vasopressin [DDAVP]) remains difficult to titrate in infants. Assess the efficacy and safety of buccally administered IN DDAVP for the management of infants with neurogenic DI. Retrospective review of clinical and laboratory data of 15 infants (mean age, 4.5 mo) with neurogenic DI treated at a tertiary care center. Treatment was with diluted IN DDAVP formulation (10 mcg/mL) administered buccally via a tuberculin syringe to the buccal mucosa. After initial DDAVP titration of 2-3 days, IN DDAVP doses ranged from 1 to 5 mcg twice daily given buccally. Mean serum sodium concentration at DI diagnosis was 159 ± 6.6 mmol/L (range, 151-178) and improved to 142 ± 3.5 mmol/L (range, 137-147) with the buccally administered IN DDAVP. Normal sodium concentrations were established without major fluctuations. Serum sodium was then maintained in the outpatient setting at a mean of 145.7 ± 4.8 mmol/L (mean duration of follow-up, 11 mo). Buccally administered IN formulation of DDAVP provides a practical and safe treatment alternative for neurogenic DI in infancy. Our approach avoided severe hypo- and hypernatremia during DDAVP titration and ongoing outpatient management of DI. The possibility for smaller dosage increments and ease of administration make IN DDAVP administered buccally preferable over other DDAVP treatment options in infants.

  8. Aerosol Route to Administer Teicoplanin in Mechanical Ventilation: In Vitro Study, Lung Deposition and Pharmacokinetic Analyses in Pigs.

    Science.gov (United States)

    Guillon, Antoine; Mercier, Emmanuelle; Lanotte, Philippe; Haguenoer, Eve; Darrouzain, François; Barc, Céline; Sarradin, Pierre; Si-Tahar, Mustapha; Heuzé-Vourc'h, Nathalie; Diot, Patrice; Vecellio, Laurent

    2015-08-01

    Glycopeptides given intravenously achieve low airway concentrations. Nebulization of teicoplanin may be an efficient way of delivering a high concentration of this antibiotic to the lung. This multistep study assessed the feasibility of teicoplanin nebulization during mechanical ventilation by evaluating: the stability of its antibiotic effect; epithelial tolerance; lung deposition and systemic absorption in ventilated pigs. Nebulized and non-nebulized teicoplanin activity was tested on Staphylococcus aureus cultures. The cytotoxic effect of teicoplanin on human respiratory epithelial cells was assessed by measuring lactate dehydrogenase activity released, cell viability, and transepithelial electrical resistance. Volume median diameter of particles of nebulized teicoplanin was measured by laser diffraction during mechanical ventilation. The deposited mass of teicoplanin nebulized with a vibrating mesh nebulizer in ventilated piglets was assessed by scintigraphy. Blood pharmacokinetics of teicoplanin administered either intravenously or by nebulization was compared. No decrease of antibiotic activity was observed after nebulization. In vitro cytotoxicity of teicoplanin was only observed with 1000 times the dose recommended for intravenous administration. Volume median diameter of particles was 2.5±0.1 μm. Of the initial nebulizer charge of teicoplanin, 24±7% was present in the lungs of ventilated pigs after the nebulization. Amount absorbed in blood was low (3.4%±0.9%) after nebulization, and blood stream elimination half-life value was 25.4 h. Teicoplanin was administered efficiently by nebulization during mechanical ventilation, without any effect on its pharmacological properties or any cytotoxicity. The pharmacokinetic parameters are promising in view of its time-dependent killing process. All the results of our multi-step study highlighted the potential of teicoplanin to be nebulized during mechanical ventilation.

  9. Effects of intravenously administered recombinant vesicular stomatitis virus (VSV(deltaM51)) on multifocal and invasive gliomas.

    Science.gov (United States)

    Lun, XueQing; Senger, Donna L; Alain, Tommy; Oprea, Andra; Parato, Kelley; Stojdl, Dave; Lichty, Brian; Power, Anthony; Johnston, Randal N; Hamilton, Mark; Parney, Ian; Bell, John C; Forsyth, Peter A

    2006-11-01

    An ideal virus for the treatment of cancer should have effective delivery into multiple sites within the tumor, evade immune responses, produce rapid viral replication, spread within the tumor, and infect multiple tumors. Vesicular stomatitis virus (VSV) has been shown to be an effective oncolytic virus in a variety of tumor models, and mutations in the matrix (M) protein enhance VSV's effectiveness in animal models. We evaluated the susceptibility of 14 glioma cell lines to infection and killing by mutant strain VSV(deltaM51), which contains a single-amino acid deletion in the M protein. We also examined the activity and safety of this strain against the U87 and U118 experimental models of human malignant glioma in nude mice and analyzed the distribution of the virus in the brains of U87 tumor-bearing mice using fluorescence labeling. Finally, we examined the effect of VSV(deltaM51) on 15 primary human gliomas cultured from surgical specimens. All statistical tests were two-sided. All 14 glioma cell lines were susceptible to VSV(deltaM51) infection and killing. Intratumoral administration of VSV(deltaM51) produced marked regression of malignant gliomas in nude mice. When administered systemically, live VSV(deltaM51) virus, as compared with dead virus, statistically significantly prolonged survival of mice with unilateral U87 tumors (median survival: 113 versus 46 days, P = .0001) and bilateral U87 tumors (median survival: 73 versus 46 days, P = .0025). VSV(deltaM51) infected multifocal gliomas, invasive glioma cells that migrated beyond the main glioma, and all 15 primary human gliomas. There was no evidence of toxicity. Systemically delivered VSV(deltaM51) was an effective and safe oncolytic agent against laboratory models of multifocal and invasive malignant gliomas, the most challenging clinical manifestations of this disease.

  10. 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...

  11. Self-administered screening for mild cognitive impairment: initial validation of a computerized test battery.

    Science.gov (United States)

    Tornatore, Jane B; Hill, Emory; Laboff, Jo Anne; McGann, Mary E

    2005-01-01

    The Computer-Administered Neuropsychological Screen for Mild Cognitive Impairment (CANS-MCI), a computer administered, scored, and interpreted touch screen battery was evaluated for its ability to detect mild cognitive impairment. Subjects were three hundred ten community-dwelling elders who enrolled in an National Institute on Aging (NIA)-funded study. One-month test-retest reliability correlations were all significant (pWeschler Memory Scale-Revised (WMS-R) LMS-II test (ptests measure the intended cognitive dimensions of memory, language/spatial fluency, and executive function/mental control. Goodness-of-fit indicators were strong (Bentler Comparative Fit Index=0.99; Root Mean Square Error of Approximation=0.055). Initial validation analyses indicate that the CANS-MCI shows promise of being a reliable, valid screening tool in determining whether more intensive testing for early cognitive impairment is warranted.

  12. Metabolic effects of growth hormone administered subcutaneously once or twice daily to growth hormone deficient adults

    DEFF Research Database (Denmark)

    Laursen, Torben; Jørgensen, Jens Otto Lunde; Christiansen, Jens Sandahl

    1994-01-01

    Abstract OBJECTIVE: The aim of this study was to compare the metabolic effects of GH administered subcutaneously either once or twice daily. The actions of GH might depend upon a pulsatile pattern of serum GH. Pulsatile and continuous intravenous delivery of GH, however, induce similar short......-term metabolic effects in GH deficient patients. An improved growth response is obtained in GH deficient children when a fixed weekly GH dose is administered by daily subcutaneous injections instead of twice or thrice-weekly intramuscular injections. A more pulsatile pattern and serum GH levels above zero might...... be achieved by further increasing the injection frequency. Increased daytime GH levels might, however, adversely affect the circadian patterns of metabolic indices, which have been demonstrated to be more successfully reproduced by evening compared with morning GH administration. DESIGN AND MEASUREMENTS...

  13. 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 (Pbuprenorphine (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.

  14. 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

  15. Pulse-Administered Toceranib Phosphate Plus Lomustine for Treatment of Unresectable Mast Cell Tumors in Dogs.

    Science.gov (United States)

    Burton, J H; Venable, R O; Vail, D M; Williams, L E; Clifford, C A; Axiak-Bechtel, S M; Avery, A C; Thamm, D H

    2015-01-01

    Nonresectable mast cell tumors (MCT) in dogs remain a therapeutic challenge, and investigation of novel combination therapies is warranted. Intermittent administration of tyrosine kinase inhibitors (TKI) combined with cytotoxic chemotherapy may effectively chemosensitize canine MCT while decreasing cost and adverse effects associated with either agent administered as monotherapy. The primary study objectives were to (1) identify the maximally tolerated dose (MTD), (2) determine the objective response rate (ORR) and (3) describe the adverse event profile of pulse-administered toceranib phosphate (TOC) combined with lomustine. Forty-seven client-owned dogs with measurable MCT. Toceranib phosphate was given PO on days 1, 3 and 5 of a 21-day cycle at a target dosage of 2.75 mg/kg. Lomustine was given PO on day 3 of each cycle at a starting dosage of 50 mg/m(2) . All dogs were concurrently treated with diphenhydramine, omeprazole, and prednisone. The MTD of lomustine was established at 50 mg/m(2) when combined with pulse-administered TOC; the dose-limiting toxicity was neutropenia. Forty-one dogs treated at the MTD were evaluable for outcome assessment. The ORR was 46% (4 complete response, 15 partial response) and the overall median progression-free survival (PFS) was 53 days (1 to >752 days). On multivariate analysis, variables significantly associated with improved PFS included response to treatment, absence of metastasis, and no previous chemotherapy. Combined treatment with pulse-administered TOC and lomustine generally is well tolerated and may be a reasonable treatment option for dogs with unresectable or metastatic MCT. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  16. 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

    2017-08-15

    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.

  17. Patients with Advanced Ovarian Cancer Administered Oral Etoposide following Taxane as Maintenance Chemotherapy

    Directory of Open Access Journals (Sweden)

    Hiroaki Nagano

    2016-03-01

    Full Text Available Introduction: The concept of maintenance therapy is one of the highly relevant approaches in the management of advanced ovarian cancer. The fundamental goal of maintenance therapy is to improve survival outcomes. We attempted to reinforce maintenance chemotherapy by adding oral etoposide following taxane administration. Cases: We retrospectively evaluated 14 patients with advanced ovarian cancer who had achieved clinically defined complete response to a primary platinum/taxane chemotherapy regimen and who were administered oral etoposide (50 mg/day × 21 days per cycle monthly for 3-5 cycles following paclitaxel or docetaxel administration as maintenance chemotherapy. With regard to oral etoposide toxicity, grade 2 oral mucositis and grade 3 anemia were observed in 1 patient each. Three to five cycles of etoposide were administered to all patients, though daily dosage was reduced to 25 mg in 2 patients due to toxicity. The median progression-free survival was 43.5 months, the median overall survival was 86 months, and 5-year overall survival was 77.1%. Conclusion: The results from this ovarian cancer treatment evaluation suggest that oral etoposide may be administered safely following paclitaxel or docetaxel as maintenance chemotherapy. We expect this regimen to contribute to the improvement in the survival outcomes of patients with advanced ovarian cancer.

  18. Meta-analysis of the effects of peer-administered psychosocial interventions on symptoms of depression.

    Science.gov (United States)

    Bryan, Amanda E B; Arkowitz, Hal

    2015-06-01

    Many community mental health centers have implemented peer treatment models that employ recovered former clients as cost-efficient adjunct providers. The effectiveness of these and other peer-administered interventions (PAIs) for treating depression symptoms has not been well-established. The current study is a meta-analysis of PAIs' effects on depression symptoms. Twenty-three eligible studies were identified. Study characteristics were coded by multiple raters, random-effects models were used to compare mean effect sizes, and mixed-effects models were used to test for moderation. PAIs produced significant pre-post reductions in depression symptoms (d = .5043 [95 % CI .3675-.6412]). In direct comparisons, PAIs performed as well as non-peer-administered interventions (.0848 [-.1455-.3151]), and significantly better than no-treatment conditions (.2011 [.0104-.3918]). PAIs that involved a professional in a secondary treatment role were significantly less effective than those that were purely peer-administered, and educational/skills-based PAIs produced better outcomes than those that were mainly supportive. Follow-up data, when available, indicated that PAIs' benefits were maintained. PAIs reduce depression symptoms and warrant further study. The clinical significance of PAIs' benefits, and whether they are better suited as stand-alone or adjunct treatments, remain to be established. Implications for the roles of mental health professionals are discussed.

  19. 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.

  20. 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.)

  1. Logistical and fiscal sustainability of a school-based, pharmacist-administered influenza vaccination program.

    Science.gov (United States)

    Fontanesi, John; Jue-Leong, Sierra

    2012-01-01

    To assess the fiscal and logistical viability of school-based, pharmacist-administered influenza vaccination programs. Econometric observational study. Nine schools in the Rincon Unified School District, Santa Rosa, CA. Safeway Pharmacies; Rincon Unified School District; California Department of Public Health, Immunization Branch; and University of California, San Diego. Assessment of direct workflow observations and administrative data. Unit costs, productivity, and effectiveness of school-based, pharmacist-administered influenza vaccination programs. The results showed a unit cost of $23.63 (compared with $25.60 for mass vaccination and $39.79 for walk-in shot-only vaccination clinics). The productivity index ($0.88) and efficiency index ($1.12) were better compared with data reported for comparable vaccination programs. School-based, pharmacist-administered vaccination programs are fiscally and logistically self-sustaining, viable alternatives to medical office-based or community-based mass vaccination clinics, and may offer a practical strategy for vaccinating children and adolescents.

  2. Research on Possible Effects of Acrylamide and Vitamin E Administered to Pregnant Rats on Placenta Tissue

    Directory of Open Access Journals (Sweden)

    Mehmet Erman Erdemli

    2017-04-01

    Full Text Available Investigate the changes that occur in the placenta tissues of pregnant rats that were administered acrylamide (AA and vitamin E as a protective agent during pregnancy. Thirty rats that were proven positive for pregnancy with vaginal smear test were randomly distributed into control, corn oil, vitamin E, acrylamide and vitamin E + acrylamide groups. Pregnant rats were decapitated on the 20th day of the experiment. Malondialdehyde (MDA, reduced glutathione (GSH, total antioxidant capacity (TAS, total oxidant capacity (TOS and Xanthine oxidase (XO levels were measured in placenta tissues. It was determined that acrylamide application during pregnancy statistically significantly increased MDA, TOS and XO levels and reduced GSH and TAS levels in the placenta tissue of pregnant rats when compared to all other groups, and GAS and TAS levels statistically significantly increased in vitamin E administered group when compared to all other groups and TOS and XO levels were decreased to control group levels. It was observed that orally administered AA changed the antioxidant / oxidant equilibrium favoring the oxidants by increasing MDA, XO and TOS levels in pregnant rats and caused oxidative stress, while vitamin E administration returned the antioxidant / oxidant equilibrium back to normal levels, preventing oxidative stress induced toxicity.

  3. Evaluation of a Self-Administered Computerized Cognitive Battery in an Older Population.

    Science.gov (United States)

    Koyama, Alain K; Hagan, Kaitlin A; Okereke, Olivia I; Weisskopf, Marc G; Rosner, Bernard; Grodstein, Francine

    2015-01-01

    The aim of this study is to assess the utility of the Cogstate self-administered computerized neuropsychological battery in a large population of older men. We invited 7,167 men (mean age of 75 years) from the Health Professionals Follow-up Study, a prospective cohort of male health professionals. We considered individual Cogstate scores and composite scores measuring psychomotor speed and attention, learning and working memory and overall cognition. Multivariate linear regression was used to assess the association between risk factors measured 4 and 28 years prior to cognitive testing and each outcome. The 1,866 men who agreed to complete Cogstate testing were similar to the 5,301 non-responders. Many expected risk factors were associated with Cogstate scores in multivariate adjusted models. Increasing age was significantly associated with worse performance on all outcomes (p 2 servings/week vs. self-administered Cogstate battery showed significant associations with several risk factors known to be associated with cognitive function. Future studies of cognitive aging may benefit from the numerous advantages of self-administered computerized testing. © 2015 S. Karger AG, Basel.

  4. 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.

  5. Rechallenge and maintenance therapy using cetuximab and chemotherapy administered to a patient with metastatic colorectal cancer.

    Science.gov (United States)

    Ma, Jian; Yang, Quan-Liang; Ling, Yang

    2017-02-14

    Cetuximab combined with chemotherapy is one of the first-line treatments of metastatic colorectal cancer. Although disease progression inevitably occurs, rechallenge and maintenance therapies using cetuximab-based regimens may be beneficial, particularly for patients with wild-type (WT) KRAS. A 47-year-old female patient who underwent right hemicolectomy presented with an ulcerative adenocarcinoma (grade 2) revealed by histopathological analysis. The patient received three cycles of adjuvant chemotherapy, but disease recurred 15 months later. Cetuximab and a FOLFOX-4 regimen were administered, followed by surgery and adjuvant chemotherapy that was administered for approximately one year. Three years after completing adjuvant therapy, her serum carcinoembryonic antigen levels rapidly increased, and enhanced computed tomography showed widespread metastases. Rechallenge with cetuximab and the FOLFIRI regimen was then initiated, and after 12 cycles, lesions in the lung and liver shrank significantly, and serum CEA levels dramatically declined. Maintenance therapy with cetuximab and capecitabine was then administered for 10 months until the metastatic lesions in the lung and liver enlarged. Rechallenge and maintenance therapy with cetuximab-based chemotherapy were relatively effective for managing a female patient with WT KRAS. Optimization of this strategy requires further in-depth investigations of more patients.

  6. 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.

  7. The effect of orally administered ranitidine and once-daily or twice-daily orally administered omeprazole on intragastric pH in cats.

    Science.gov (United States)

    Šutalo, S; Ruetten, M; Hartnack, S; Reusch, C E; Kook, P H

    2015-01-01

    Gastric acid suppressants frequently are used in cats with acid-related gastric disorders. However, it is not known if these drugs effectively increase intragastric pH in cats. To examine the effects of PO administered ranitidine and omeprazole on intragastric pH in cats and to compare the efficacy of once-daily versus twice-daily dosage regimens for omeprazole. Eight domestic shorthair cats. Using a randomized 4-way cross-over design, cats were given enteric-coated omeprazole granules (1.1-1.3 mg/kg q24h and q12h), ranitidine (1.5-2.3 mg/kg q12h), and placebo. Intragastric pH was monitored continuously for 96 hours using the Bravo(™) system, starting on day 4 of treatment, followed by a median washout period of 12 days. Mean percentage of time pH was ≥3 and ≥4 was compared among groups using repeated measures ANOVA. Mean ± SD percentage of time intragastric pH was ≥3 and ≥4 was 67.0 ± 24.0% and 54.6 ± 26.4% for twice-daily omeprazole, 24.4 ± 22.8% and 16.8 ± 19.3% for once-daily omeprazole, 16.5 ± 9.0% and 9.6 ± 5.9% for ranitidine, and 9.4 ± 8.0% and 7.0 ± 6.6% for placebo administration. Twice-daily omeprazole treatment significantly increased intragastric pH, whereas pH after once-daily omeprazole and ranitidine treatments did not differ from that of placebo-treated cats. Only twice-daily PO administered omeprazole significantly suppressed gastric acidity in healthy cats, whereas once-daily omeprazole and standard dosages of ranitidine were not effective acid suppressants in cats. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

  8. 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...

  9. 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

    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...... the area of punctate-evoked hyperalgesia significantly. It tended to reduce VAS scores of spontaneous pain but had no effect on evoked pain. The differential effects of ketamine and lidocaine on static and dynamic hyperalgesia suggest that the two types of hyperalgesia are mediated by separate mechanisms...

  10. Standardization of Administered Activities in Pediatric Nuclear Medicine: A Report of the First Nuclear Medicine Global Initiative Project, Part 2-Current Standards and the Path Toward Global Standardization.

    Science.gov (United States)

    Fahey, Frederic H; Bom, Henry Hee-Seung; Chiti, Arturo; Choi, Yun Young; Huang, Gang; Lassmann, Michael; Laurin, Norman; Mut, Fernando; Nuñez-Miller, Rodolfo; O'Keeffe, Darin; Pradhan, Prasanta; Scott, Andrew M; Song, Shaoli; Soni, Nischal; Uchiyama, Mayuki; Vargas, Luis

    2016-07-01

    The Nuclear Medicine Global Initiative (NMGI) was formed in 2012 and consists of 13 international organizations with direct involvement in nuclear medicine. The underlying objectives of the NMGI are to promote human health by advancing the field of nuclear medicine and molecular imaging, encourage global collaboration in education, and harmonize procedure guidelines and other policies that ultimately lead to improvements in quality and safety in the field throughout the world. For its first project, the NMGI decided to consider the issues involved in the standardization of administered activities in pediatric nuclear medicine. It was decided to divide the final report of this project into 2 parts. Part 1 was published in this journal in the spring of 2015. This article presents part 2 of the final report. It discusses current standards for administered activities in children and adolescents that have been developed by various professional organizations. It also presents an evaluation of the current practice of pediatric nuclear medicine specifically with regard to administered activities as determined by an international survey of 313 nuclear medicine clinics and centers from 29 countries. Lastly, it provides recommendations for a path toward global standardization of the administration of radiopharmaceuticals in children. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  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. Methoxetamine, a ketamine derivative, produced conditioned place preference and was self-administered by rats: Evidence of its abuse potential.

    Science.gov (United States)

    Botanas, Chrislean Jun; de la Peña, June Bryan; Dela Peña, Irene Joy; Tampus, Reinholdgher; Yoon, Robin; Kim, Hee Jin; Lee, Yong Sup; Jang, Choon Gon; Cheong, Jae Hoon

    2015-06-01

    Methoxetamine (MXE) is an N-methyl-d-aspartate (NMDA) receptor antagonist that is chemically and pharmacologically similar to ketamine. Recently, there have been many reports regarding its use/misuse in humans which have resulted in serious or even fatal outcomes. Despite these reports, MXE is not controlled or regulated in many countries which may be partly due to the lack of scientific evidence regarding its abuse potential. Thus, in the present study we evaluated the abuse potential (rewarding and reinforcing effects) of MXE through the conditioned place preference (CPP) and self-administration (SA) tests in Sprague-Dawley rats. In addition, locomotor activity during the conditioning phase of the CPP was also analyzed. Ketamine was used as a reference drug. MXE (2.5 and 5mg/kg) induced significant CPP in rats, an effect comparable to that of ketamine (5mg/kg). Interestingly, MXE did not produce any locomotor alterations while ketamine decreased the locomotor activity of rats. In the SA test, rats showed modest self-administration of MXE (0.25, 0.5, 1.0mg/kg/infusion), while ketamine (0.5mg/kg/infusion) was robustly self-administered. These results demonstrate that MXE, similar to ketamine, has rewarding and reinforcing effects in rats. The present study strongly suggests that MXE has a potential for human abuse. In addition, the discrepant effects of MXE and ketamine on locomotor activity and rate of self-administration propose that the psychopharmacological effects of these drugs may diverge in some aspects. More importantly, this study advocates the careful monitoring and prompt regulation of MXE and its related substances. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Nonclinical evaluation of CNS-administered TPP1 enzyme replacement in canine CLN2 neuronal ceroid lipofuscinosis.

    Science.gov (United States)

    Vuillemenot, Brian R; Kennedy, Derek; Cooper, Jonathan D; Wong, Andrew M S; Sri, Sarmi; Doeleman, Thom; Katz, Martin L; Coates, Joan R; Johnson, Gayle C; Reed, Randall P; Adams, Eric L; Butt, Mark T; Musson, Donald G; Henshaw, Joshua; Keve, Steve; Cahayag, Rhea; Tsuruda, Laurie S; O'Neill, Charles A

    2015-02-01

    The CLN2 form of neuronal ceroid lipofuscinosis, a type of Batten disease, is a lysosomal storage disorder caused by a deficiency of the enzyme tripeptidyl peptidase-1 (TPP1). Patients exhibit progressive neurodegeneration and loss of motor, cognitive, and visual functions, leading to death by the early teenage years. TPP1-null Dachshunds recapitulate human CLN2 disease. To characterize the safety and pharmacology of recombinant human (rh) TPP1 administration to the cerebrospinal fluid (CSF) as a potential enzyme replacement therapy (ERT) for CLN2 disease, TPP1-null and wild-type (WT) Dachshunds were given repeated intracerebroventricular (ICV) infusions and the pharmacokinetic (PK) profile, central nervous system (CNS) distribution, and safety were evaluated. TPP1-null animals and WT controls received 4 or 16mg of rhTPP1 or artificial cerebrospinal fluid (aCSF) vehicle every other week. Elevated CSF TPP1 concentrations were observed for 2-3 days after the first ICV infusion and were approximately 1000-fold higher than plasma levels at the same time points. Anti-rhTPP1 antibodies were detected in CSF and plasma after repeat rhTPP1 administration, with titers generally higher in TPP1-null than in WT animals. Widespread brain distribution of rhTPP1 was observed after chronic administration. Expected histological changes were present due to the CNS delivery catheters and were similar in rhTPP1 and vehicle-treated animals, regardless of genotype. Neuropathological evaluation demonstrated the clearance of lysosomal storage, preservation of neuronal morphology, and reduction in brain inflammation with treatment. This study demonstrates the favorable safety and pharmacology profile of rhTPP1 ERT administered directly to the CNS and supports clinical evaluation in patients with CLN2 disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. In vivo curative and protective potential of orally administered 5-aminolevulinic acid plus ferrous ion against malaria.

    Science.gov (United States)

    Suzuki, Shigeo; Hikosaka, Kenji; Balogun, Emmanuel O; Komatsuya, Keisuke; Niikura, Mamoru; Kobayashi, Fumie; Takahashi, Kiwamu; Tanaka, Tohru; Nakajima, Motowo; Kita, Kiyoshi

    2015-11-01

    5-Aminolevulinic acid (ALA) is a naturally occurring amino acid present in diverse organisms and a precursor of heme biosynthesis. ALA is commercially available as a component of cosmetics, dietary supplements, and pharmaceuticals for cancer diagnosis and therapy. Recent reports demonstrated that the combination of ALA and ferrous ion (Fe(2+)) inhibits the in vitro growth of the human malaria parasite Plasmodium falciparum. To further explore the potential application of ALA and ferrous ion as a combined antimalarial drug for treatment of human malaria, we conducted an in vivo efficacy evaluation. Female C57BL/6J mice were infected with the lethal strain of rodent malaria parasite Plasmodium yoelii 17XL and orally administered ALA plus sodium ferrous citrate (ALA/SFC) as a once-daily treatment. Parasitemia was monitored in the infected mice, and elimination of the parasites was confirmed using diagnostic PCR. Treatment of P. yoelii 17XL-infected mice with ALA/SFC provided curative efficacy in 60% of the mice treated with ALA/SFC at 600/300 mg/kg of body weight; no mice survived when treated with vehicle alone. Interestingly, the cured mice were protected from homologous rechallenge, even when reinfection was attempted more than 230 days after the initial recovery, indicating long-lasting resistance to reinfection with the same parasite. Moreover, parasite-specific antibodies against reported vaccine candidate antigens were found and persisted in the sera of the cured mice. These findings provide clear evidence that ALA/SFC is effective in an experimental animal model of malaria and may facilitate the development of a new class of antimalarial drug. Copyright © 2015, Suzuki et al.

  15. 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

  16. Validation of a Self-Administered Audiometry Application: An Equivalence Study.

    Science.gov (United States)

    Whitton, Jonathon P; Hancock, Kenneth E; Shannon, Jeffrey M; Polley, Daniel B

    2016-10-01

    To compare hearing measurements made at home using self-administered audiometric software against audiological tests performed on the same subjects in a clinical setting Prospective, crossover equivalence study In experiment 1, adults with varying degrees of hearing loss (N = 19) performed air-conduction audiometry, frequency discrimination, and speech recognition in noise testing twice at home with an automated tablet application and twice in sound-treated clinical booths with an audiologist. The accuracy and reliability of computer-guided home hearing tests were compared to audiologist administered tests. In experiment 2, the reliability and accuracy of pure-tone audiometric results were examined in a separate cohort across a variety of clinical settings (N = 21). Remote, automated audiograms were statistically equivalent to manual, clinic-based testing from 500 to 8,000 Hz (P ≤ .02); however, 250 Hz thresholds were elevated when collected at home. Remote and sound-treated booth testing of frequency discrimination and speech recognition thresholds were equivalent (P ≤ 5 × 10(-5) ). In the second experiment, remote testing was equivalent to manual sound-booth testing from 500 to 8,000 Hz (P ≤ .02) for a different cohort who received clinic-based testing in a variety of settings. These data provide a proof of concept that several self-administered, automated hearing measurements are statistically equivalent to manual measurements made by an audiologist in the clinic. The demonstration of statistical equivalency for these basic behavioral hearing tests points toward the eventual feasibility of monitoring progressive or fluctuant hearing disorders outside of the clinic to increase the efficiency of clinical information collection. 2b. Laryngoscope, 126:2382-2388, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  17. 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

  18. Osteopathic Medical Student Administered Smoking Cessation Counseling is an Effective Tool.

    Science.gov (United States)

    Capozzi, Barbara; Chez, Ariel; Carpenter, Taissia; Hubert, Laura; Hewan-Lowe, Lissa; Ozcan, Asli; Sahni, Sonu

    2016-04-01

    Physician counseling on the risks of tobacco smoking and the benefits of cessation has been shown to be an effective method of increasing the rate of smoking cessation. Using the "Help Your Patients Quit Smoking: A Coaching Guide" also referred to as the "7A's of Smoking Cessation" guideline from the New York City Department of Health and Mental Hygiene is thought to be effective to convey the importance of smoking cessation. To study the efficacy of the "7A's of Smoking Cessation" guideline counseling conducted by osteopathic medical students. Osteopathic medical students were trained to counsel smokers for 3-10 min based on New York City Department of Health's "7A's of Smoking Cessation" guidelines by a licensed physician. Students then counseled health fair participants who were cigarette smokers for 3-10 min. Postcounseling, participants were administered an 4 question survey to evaluate the effect counseling had on their desire to quit smoking. Survey data were collected and analyzed. Institutional Review Board approval was obtained for this study. A total of 13 anonymous health fair participants who were also smokers were administered both counseling sessions and surveys. 11/13 (84.6%) participants stated that the session motivated them to quit smoking. 9/13 (69.2%) participants responded that they were now motivated to discuss smoking cessation with their doctor after being counseled. Of these participants 12/13 (92.3%) had previously attempted to quit smoking without success. Participants reported an increased willingness to stop smoking after being counseled by osteopathic medical students. Participants also reported an increased motivation to discuss smoking cessation with their physician. These findings indicate that smoking cessation counseling administered by osteopathic medical students effectively in encouraging smokers to consider reduction or cessation of tobacco use.

  19. Activation of central nesfatin-1/NucB2 after intraperitoneally administered cisplatin in rats.

    Science.gov (United States)

    Akiyama, Yasuki; Yoshimura, Mitsuhiro; Nishimura, Kazuaki; Nishimura, Haruki; Sonoda, Satomi; Ueno, Hiromichi; Mitojima, Yasuhito; Saito, Reiko; Maruyama, Takashi; Nonaka, Yuki; Hashimoto, Hirofumi; Uezono, Yasuhito; Hirata, Keiji; Ueta, Yoichi

    2017-08-26

    Cisplatin, known as an anticancer drug, has been widely used; however, diverse disadvantageous side effects, including appetite loss, afflict patients. Nesfatin-1/NucB2, discovered as an anorexic neuropeptide, is broadly expressed in the central nervous system (CNS) and peripheral organ. In the present study, we examined the effects of intraperitoneally (i.p.) administered cisplatin on central nesfatin-1/NucB2. Saline, as control, or cisplatin (6 mg/kg dissolved in saline) was i.p. administered in adult male Wistar rats (180-220 g). Cumulative food intake was remarkably suppressed for at least 24 h and body weight was significantly smaller at 24 h after i.p. administration of cisplatin compared to control group. At 90 min after i.p. administration, they were perfused, followed by carrying out double-immunohistochemistry for Fos and nesfatin-1/NucB2. The percentage of nesfatin-1/NucB2 immunoreactive neurons expressing Fos was marked increased in the hypothalamus and brainstem after i.p. administration of cisplatin. Intracerebroventricularlly administered nesfatin-1/NucB2-antisense resulted in a significant attenuation of decreased food intake for 2 h after i.p. administration of cisplatin compared to nesfatin-1/NucB2-missense treated group. These results suggest that i.p. administration of cisplatin activated, at least in part, nesfatin-1/NucB2 neuron in the CNS and may exert anorexigenic effects in rats. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Evaluation of factors important in modeling plasma concentrations of tetracycline hydrochloride administered in water in swine.

    Science.gov (United States)

    Mason, Sharon E; Almond, Glen W; Riviere, Jim E; Baynes, Ronald E

    2012-10-01

    To model the plasma tetracycline concentrations in swine (Sus scrofa domestica) treated with medication administered in water and determine the factors that contribute to the most accurate predictions of measured plasma drug concentrations. Plasma tetracycline concentrations measured in blood samples from 3 populations of swine. Data from previous studies provided plasma tetracycline concentrations that were measured in blood samples collected from 1 swine population at 0, 4, 8, 12, 24, 32, 48, 56, 72, 80, 96, and 104 hours and from 2 swine populations at 0, 12, 24, 48, and 72 hours hours during administration of tetracycline hydrochloride dissolved in water. A 1-compartment pharmacostatistical model was used to analyze 5 potential covariate schemes and determine factors most important in predicting the plasma concentrations of tetracycline in swine. 2 models most accurately predicted the tetracycline plasma concentrations in the 3 populations of swine. Factors of importance were body weight or age of pig, ambient temperature, concentration of tetracycline in water, and water use per unit of time. The factors found to be of importance, combined with knowledge of the individual pharmacokinetic and chemical properties of medications currently approved for administration in water, may be useful in more prudent administration of approved medications administered to swine. Factors found to be important in pharmacostatistical models may allow prediction of plasma concentrations of tetracycline or other commonly used medications administered in water. The ability to predict in vivo concentrations of medication in a population of food animals can be combined with bacterial minimum inhibitory concentrations to decrease the risk of developing antimicrobial resistance.

  1. Lymphatic fat absorption varies among rats administered dairy products differing in physiochemical properties

    DEFF Research Database (Denmark)

    Fruekilde, Maj-Britt; Høy, Carl-Erik

    2004-01-01

    , these results demonstrated different lymphatic absorption patterns of fat from dairy products differing in physiochemical properties. Because the fatty acid composition of the dairy products differed only slightly, other factors such as viscosity, type of emulsion, particle size, and likely also protein content......We examined in rats the intestinal absorption of fat from dairy products differing in physiochemical properties. Five dairy products (cream cheese, cream, sour cream, butter, and mixed butter) with minor differences in fatty acid composition were administered by gavage to rats, and lymphatic fat...

  2. Comparing portable computers with bedside computers when administering medications using bedside medication verification.

    Science.gov (United States)

    Ludwig-Beymer, Patti; Williams, Phillip; Stimac, Ellen

    2012-01-01

    This research examined bedside medication verification administration in 2 adult critical care units, using portable computers and permanent bedside computers. There were no differences in the number of near-miss errors, the time to administer the medications, or nurse perception of ease of medication administration, care of patients, or reliability of technology. The percentage of medications scanned was significantly higher with the use of permanent bedside computers, and nurses using permanent bedside computers were more likely to agree that the computer was always available.

  3. Community Cognitive Screening Using the Self-Administered Gerocognitive Examination (SAGE).

    Science.gov (United States)

    Scharre, Douglas W; Chang, Shu Ing; Nagaraja, Haikady N; Yager-Schweller, Jennifer; Murden, Robert A

    2014-01-01

    This study investigated the functionality of the Self-Administered Gerocognitive Examination (SAGE) for cognitive screening in community settings and examined its characteristics as a cognitive screening assessment tool. From 45 community events, 1,047 individuals over age 50 were screened with SAGE. Cognitive impairment was identified in 28%. Principal-component and correlation analysis indicate that SAGE is an internally-consistent test that is very well balanced, with language, cognition, visuospatial, executive, and memory domains. Community cognitive screening using SAGE was found to be feasible and efficient in diverse settings with both small and large groups.

  4. A Review of "Challenging Situations When Administering Palliative 
Chemotherapy--A Nursing Perspective".

    Science.gov (United States)

    Houlihan, Nancy G

    2015-05-01

    The December 2014 issue of the European Journal of Oncology Nursing published an article by Näppä, Rasmussen, Axelsson, and Lindqvist that reported on a qualitative study of the challenges experienced by Swedish nurses when administering palliative cancer treatment at the end of life. The study identified the various clinical scenarios that create dilemmas among nurses. The authors described why chemotherapy at the end of life has become so prevalent and offered strategies to minimize or prevent the moral distress that can occur. Research from the United States identified similar trends in end-of-life treatment and supportive recommendations for multidisciplinary palliative care team collaboration as a solution.

  5. Relative bioavailability in man of noscapine administered in lozenges and mixture

    DEFF Research Database (Denmark)

    Jensen, L.N.; Christrup, Lona Louring; Jacobsen, L.

    1992-01-01

    The bioavailability of noscapine base administered in lozenges in a dose of 100 mg to twelve healthy volunteers, in a study using an open balanced cross-over design, was compared with that of 100 mg of noscapine hydrochloride given perorally as a mixture. The bioavailability of noscapine after...... administration in lozenges was significantly higher than that after administration of the drug as a mixture. It is concluded that the lozenges containing noscapine base may be a valuable alternative to the conventional noscapine hydrochloride mixture....

  6. 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...... of perforations caused by an experienced or less experienced endoscopist (p = 0.589). Conclusion. The risk of colonic perforations during colonoscopy was not found to be significantly higher in patients undergoing NAPS compared to patients undergoing conventional sedation, although a tendency may exist...

  7. 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

    Abstract Objective. Standard benzodiazepine/opioid cocktail has proven inferior to propofol sedation during complicated endoscopic procedures and in low-tolerance patients. Propofol is a short-acting hypnotic with a potential risk of respiratory depression at levels of moderate to deep sedation....... 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...

  8. Comparison of Anglo- and Mexican-Americans on the 16PF administered in Spanish or English.

    Science.gov (United States)

    Whitworth, R H; Perry, S M

    1990-11-01

    The 16PF was administered in either Spanish or English to 546 Anglo- or Mexican-Americans separated into three ethnicity/test language groups: Anglos tested in English, Mexican-Americans tested in Spanish, and Mexican-Americans tested in English. Multivariate and univariate statistics revealed significant differences among the three groups. The largest number of scale differences was between Anglos and Mexican-Americans tested in Spanish. The second largest number of differences was found between the two Mexican-American groups, and the smallest number of differences was found between Anglos and Hispanics tested in English.

  9. Foundation doctors in Anaesthesia: should they be taught to administer an anaesthetic?

    Directory of Open Access Journals (Sweden)

    Williamson Sean

    2007-11-01

    Full Text Available Abstract Background Anaesthetic pre-registration house officer posts have been available since 1997. With the change to postgraduate medical training introduced in 2005, these posts have become vital building blocks for Foundation Programmes. Discussion We debate the skills that new Foundation Programme doctors in such posts should be taught, particularly whether administration of an anaesthetic holds an important place. The opinion of college tutors prior to the institution of the foundation programme is included. These were obtained from a postal questionnaire. Summary We maintain that teaching how to administer an anaesthetic remains an important learning objective and something that should be actively pursued.

  10. 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....

  11. A Comparison of the Pencil-and-Paper and Computer-Administered Minnesota Multiphasic Personality Inventory-Adolescent

    Science.gov (United States)

    Hays, Shannon; McCallum, R. Steve

    2005-01-01

    Within the context of a counterbalanced design, 102 students from either a high school or a large Southeastern university were administered two versions of the Minnesota Multiphasic Personality Inventory-Adolescent (MMPI-A): a computer-administered version (CA) and a paper-and-pencil version (PAP). Time between testing sessions was approximately…

  12. 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 ...

  13. 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...

  14. 40 CFR 147.2550 - State-administered program-Class I, III, IV and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Wyoming § 147.2550 State-administered program—Class I, III, IV and V wells. The UIC program for Class I, III, IV and V wells in the State of Wyoming, except those on Indian lands is the... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I...

  15. 40 CFR 147.251 - EPA-administered program-Class I, III, IV and V wells and Indian lands.

    Science.gov (United States)

    2010-07-01

    ... INJECTION CONTROL PROGRAMS California § 147.251 EPA-administered program—Class I, III, IV and V wells and Indian lands. (a) Contents. The UIC program in the State of California for Class I, III, IV and V wells... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Class I, III...

  16. 40 CFR 147.2650 - State-administered program-Class I, II, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Puerto Rico § 147.2650 State-administered program—Class I, II, III, IV, and V wells. The... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I, II, III, IV, and V wells. 147.2650 Section 147.2650 Protection of Environment ENVIRONMENTAL PROTECTION...

  17. 40 CFR 147.500 - State-administered program-Class I, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Florida § 147.500 State-administered program—Class I, III, IV, and V wells. The UIC program for Class I, III, IV, and V wells in the State of Florida, except for those on Indian lands is... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I...

  18. 40 CFR 147.1601 - State-administered program-Class I, III, IV and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS New Mexico § 147.1601 State-administered program—Class I, III, IV and V wells. The UIC program for Class I, III, IV and V injection wells in the State of New Mexico, except for those on Indian... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I...

  19. 40 CFR 147.1301 - State-administered program-Class I, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Missouri § 147.1301 State-administered program—Class I, III, IV, and V wells. The UIC program for Class I, III, IV, and V wells in the State of Missouri, other than those on Indian lands, is... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I...

  20. 40 CFR 147.301 - EPA-administered program-Class I, III, IV, V wells and Indian lands.

    Science.gov (United States)

    2010-07-01

    ... INJECTION CONTROL PROGRAMS Colorado § 147.301 EPA-administered program—Class I, III, IV, V wells and Indian lands. (a) Contents. The UIC program for Class I, III, IV and V wells on all lands in Colorado... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Class I, III...

  1. 40 CFR 147.1850 - State-administered program-Class I, III, IV and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Oklahoma § 147.1850 State-administered program—Class I, III, IV and V wells. The UIC program for Class I, III, IV, and V wells in the State of Oklahoma, except those on Indian lands, is the... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I...

  2. 40 CFR 147.1751 - State-administered program-Class I, III, IV and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS North Dakota § 147.1751 State-administered program—Class I, III, IV and V wells. The UIC program for Class I, III, IV, and V wells in the State of North Dakota, except those on Indian lands, is... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I...

  3. 40 CFR 147.200 - State-administered program-Class I, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Arkansas § 147.200 State-administered program—Class I, III, IV, and V wells. The UIC program for Class I, III, IV and V wells in the State of Arkansas, except those wells on Indian lands, is... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I...

  4. 34 CFR 462.41 - How must tests be administered in order to accurately measure educational gain?

    Science.gov (United States)

    2010-07-01

    ... real time; however, for such an instrument, the size of the item pool and the method of item selection... must administer a test using only staff who have been trained to administer the test. (2) A local... the Office of Management and Budget under control number 1830-0027) (Authority: 20 U.S.C. 9212) ...

  5. 40 CFR 147.700 - State-administered program-Class I, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Illinois § 147.700 State-administered program—Class I, III, IV, and V wells. The UIC program for Class I, III, IV and V wells in the State of Illinois, except those on Indian lands, is the... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I...

  6. 40 CFR 147.2000 - State-administered program-Class I, II, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Rhode Island § 147.2000 State-administered program—Class I, II, III, IV, and V wells. The... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I, II, III, IV, and V wells. 147.2000 Section 147.2000 Protection of Environment ENVIRONMENTAL PROTECTION...

  7. 40 CFR 147.1250 - State-administered program-Class I, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Mississippi § 147.1250 State-administered program—Class I, III, IV, and V wells. The UIC program for Class I, III, IV and V wells in the State of Mississippi, except those on Indian lands, is the... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I...

  8. Validation of the GSFQ, a Self-Administered Symptom Frequency Questionnaire for Patients with Gastroesophageal Reflux Disease

    Directory of Open Access Journals (Sweden)

    Pierre Paré

    2003-01-01

    Full Text Available BACKGROUND: Although the diagnosis of gastroesophageal reflux disease (GERD is based primarily on symptoms experienced by a patient, relatively little attention has been paid to the development and validation of self-administered questionnaires specific to GERD symptoms. The present article presents the validation of the short, self-administered GERD Symptom Frequency Questionnaire (GSFQ.

  9. Evaluation of dexamethasone on fetal maturation and delivery in mares when administered on days 305 to 307 of gestation

    Science.gov (United States)

    In many species corticosteroids are administered to the dam to induce precocious fetal maturation when the pregnancy is at risk; however in the mare this has met with mixed results. Previously we showed that 24 mg betamethasone administered to pregnant mares on d305 to 307 of pregnancy tended to...

  10. Biorelevant in vitro performance testing of orally administered dosage forms-workshop report.

    Science.gov (United States)

    Reppas, Christos; Friedel, Horst-Dieter; Barker, Amy R; Buhse, Lucinda F; Cecil, Todd L; Keitel, Susanne; Kraemer, Johannes; Morris, J Michael; Shah, Vinod P; Stickelmeyer, Mary P; Yomota, Chikako; Brown, Cynthia K

    2014-07-01

    Biorelevant in vitro performance testing of orally administered dosage forms has become an important tool for the assessment of drug product in vivo behavior. An in vitro performance test which mimics the intraluminal performance of an oral dosage form is termed biorelevant. Biorelevant tests have been utilized to decrease the number of in vivo studies required during the drug development process and to mitigate the risk related to in vivo bioequivalence studies. This report reviews the ability of current in vitro performance tests to predict in vivo performance and generate successful in vitro and in vivo correlations for oral dosage forms. It also summarizes efforts to improve the predictability of biorelevant tests. The report is based on the presentations at the 2013 workshop, Biorelevant In Vitro Performance Testing of Orally Administered Dosage Forms, in Washington, DC, sponsored by the FIP Dissolution/Drug Release Focus Group in partnership with the American Association of Pharmaceutical Scientists (AAPS) and a symposium at the AAPS 2012 Annual meeting on the same topic.

  11. 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.

  12. Non-surgical periodontal therapy supplemented with systemically administered azithromycin: a systematic review of RCTs.

    Science.gov (United States)

    Buset, Sabrina L; Zitzmann, Nicola U; Weiger, Roland; Walter, Clemens

    2015-11-01

    Azithromycin may be an alternative adjunctive systemic antibiotic in non-surgical periodontal therapy. This study aims to identify randomized controlled trials evaluating non-surgical periodontal treatment of chronic and/or aggressive periodontitis supplemented with systemically administered azithromycin. A systematic literature search was performed for publications published by 31 March 2014 using electronic databases and hand search. Randomized controlled trials published in English or German language, with a follow-up ≥6 months were included. From 231 titles identified, nine publications were eligible for inclusion. Among the studies included, showing some risk of bias, seven reported on patients with chronic periodontitis and two with aggressive periodontitis. Minor adverse events were described in five studies. A synthesis of results using a vote counting method was applied. Significant (p azithromycin were shown in six studies for probing depth changes and in five studies for clinical attachment level changes. In contrast to aggressive periodontitis patients, data from this analysis indicate a potential benefit of systemic azithromycin as adjunctive to non-surgical periodontal therapy in chronic periodontitis patients. When contraindications for the standard antibiotics are present, azithromycin (AZM) may be considered as alternative systemically administered antibiotic drug in selected cases of chronic periodontitis.

  13. 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.

  14. Influence of glutathione on the bioactivity of subcutaneously or orally administered insulin to rats.

    Science.gov (United States)

    Al-Kurdi, Zakieh I; Chowdhry, Babur Z; Leharne, Stephen A; Qinna, Nidal A; Al-Omari, Mahmoud M H; Badwan, Adnan A

    2015-01-01

    The effect of reduced (GSH) and oxidized (GSSG) glutathione on the bioactivity of insulin was studied. A polyelectrolyte complex (PEC) of insulin with low molecular weight chitosan (13 kDa) was prepared and characterized. The PEC was then solubilized, in the presence and absence of GSH and GSSG, in a reverse micelle consisting of oleic acid and two surfactants (PEG-8 caprylic/capric glycerides and polyglycerol-6-dioleate). The in vitro and in vivo performances of the reverse micelle formulations (RMFs) were evaluated in rats. At pH 6.5 the association efficiency of the PEC was 76.2%. In vitro insulin release from the RMs was negligible at pH 1.2 and was markedly increased at pH 6.8. The hypoglycemic activity of insulin in the PEC was reduced when administered via the subcutaneous route, regardless of the GSH content. On the other hand, the presence of GSSG significantly enhanced hypoglycemia. When the RMF was administered via the oral route, the presence of GSH had no effect on the hypoglycemic activity of insulin compared with the GSH free system. However, the presence of GSSG in the oral preparation increased the hypoglycemic activity of insulin; probably by inhibiting insulin degradation, thereby prolonging its effect. Thus, incorporation of GSSG in the RMF reduces blood glucose levels in rats and protects insulin from degradation.

  15. Fate of orally administered {sup 15}N-labeled polyamines in rats bearing solid tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Masaki; Samejima, Keijiro; Goda, Hitomi; Niitsu, Masaru [Josai Univ., Sakado, Saitama (Japan). Faculty of Pharmaceutical Sciences; Xu Yongji [Qingdao Univ. of Science and Technology (China). Inst. of Chemical and Molecular Technology; Takahashi, Masakazu [Sasaki Inst., Tokyo (Japan); Hashimoto, Yoshiyuki [Kyoritsu Coll. of Pharmacy, Tokyo (Japan)

    2003-03-01

    We studied absorption, distribution, metabolism, and excretion of polyamines (putrescine, spermidine, and spermine) in the gastrointestinal tract using {sup 15}N-labeled polyamines as tracers and ionspray ionization mass spectrometry (IS-MS). The relatively simple protocol using rats bearing solid tumors provided useful information. Three {sup 15}N-labeled polyamines that were simultaneously administered were absorbed equally from gastrointestinal tract, and distributed within tissues at various concentrations. The uptake of {sup 15}N-spermidine seemed preferential to that of {sup 15}N-spermine since the concentrations of {sup 15}N-spermidine in the liver and tumors were higher, whereas those of {sup 15}N-spermine were higher in the kidney, probably due to the excretion of excess extracellular spermine. Most of the absorbed {sup 15}N-putrescine seemed to be lost, suggesting blood and tissue diamine oxidase degradation. Concentrations of {sup 15}N-spermidine and {sup 15}N-spermine in the tumor were low. We also describe the findings from two rats that were administered with {sup 15}N-spermine. The tissue concentrations of {sup 15}N-spermine were unusually high, and significant levels of {sup 15}N-spermidine were derived from {sup 15}N-spermine in these animals. (author)

  16. Mood changes by self-administered acupressure in Japanese college students: a randomized controlled trial.

    Science.gov (United States)

    Horiuchi, Satoshi; Tsuda, Akira; Honda, Yasuhiro; Kobayashi, Hisanori; Naruse, Mayu; Tsuchiyagaito, Aki

    2014-12-17

    The aim of this 2-week study was to examine the effects of self-administered acupressure intervention onlevels of mood of 54 students (34 males and 20 females) majoring in acupuncture and moxibustion medicineat a college located in Fukuoka, Japan. Eligibility criteria were the ability to complete the intervention accurately and no history of psychiatric diseases. The students were randomly assigned to one of the two groups: an intervention group (IG, n = 28) and a control group (CG, n = 26). The IG participants completed fiveacupressure sessions three times a day (morning, noon, and night), involving the application of pressure to six acupuncture points (GB12, SI17, and LI18 according to 2008 World Health OrganizationRegional Office in the Western Pacific standard), three on the left and three on the right side of the neck for 5 s each. The CG participants were requested to spend their time as usual. Self-reported levels of tension-anxiety, depression-dejection, anger-hostility, vigor, fatigue, and confusion over the past week were measured before and after the study as the main outcomes. Side effects were not predicted and not assessed. The retention rate of this trial was 100%. Improvements in mood, defined as a change from baseline to 2 weeks later, were significantly greater in IG. Our results showed that self-administered intervention had the ability to alter mood levels in college students.

  17. Does desloratadine alter the serum levels of montelukast when administered in a fixed-dose combination?

    Science.gov (United States)

    Cingi, Cemal; Toros, Sema Zer; Ince, Iskender; Ertugay, Cigdem Kalaycik; Gurbuz, M Kezban; Cakli, Hamdi; Erdogmus, Nagehan; Karasulu, Ercument; Kaya, Ercan

    2013-11-01

    The aim of this study was to investigate the serum levels of montelukast when administered alone or in combination with desloratadine. A prospective crossover study. Twenty-three healthy volunteers were investigated in two sessions. Volunteers were given 10 mg of montelukast orally with 250 mL water in the first session. The same subjects were given 10 mg of montelukast in fixed combination with 5 mg desloratadine 10 days after first session. Blood samples were collected 2, 3, and 4 hours after drug administration, and kept at -80°C after both applications. Plasma samples were analyzed for montelukast concentration. Mean concentration values of both groups were not statistically different (P > .05), but the differences were statistically significant according to time (P .05). The absorption rate of montelukast was not altered when administered with desloratadine. This study suggested that desloratadine does not influence the bioavailability of montelukast, and their combination therapy can be used safely. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  18. 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.

  19. Applications for self-administered mobile cognitive assessments in clinical research: A systematic review.

    Science.gov (United States)

    Moore, Raeanne C; Swendsen, Joel; Depp, Colin A

    2017-12-01

    Frequent, brief and repeated self-administered mobile assessments of cognitive function, conducted in everyday life settings, are a promising complementary tool to traditional assessment approaches. Mobile cognitive assessments promote patient-centered care and might enhance capacity to inform individual-level outcomes over time (i.e. detecting subtle declines in cognitive function), as well as in assessing cognition and its correlates in the naturalistic environment. The goal of this systematic review was to assess the feasibility and psychometric properties of mobile cognitive assessments. Through a comprehensive search, we identified 12 articles using self-administered, mobile phone-based cognitive assessments. Studies sampled participants between 1 and 6 times per day for 1-14 days. Samples ranged in age from 14 to 83 years old and were generally healthy populations without cognitive impairment. Working memory was the most frequently-assessed cognitive domain (n = 7), followed by attention/reaction time (n = 4). Seven studies reported adherence, with mean adherence rates of 79.2%. In addition to positive evidence of feasibility, there was general support for high levels of between- and within-person reliability and construct validity. While research has only begun to explore the utility of mobile cognitive assessments, studies to-date indicate they may be a promising complementary tool to traditional assessment methods with potential to improve clinical care and research. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Tuberculosis treatment outcomes: directly observed therapy compared with self-administered therapy.

    Science.gov (United States)

    Jasmer, Robert M; Seaman, Christopher B; Gonzalez, Leah C; Kawamura, L Masae; Osmond, Dennis H; Daley, Charles L

    2004-09-01

    Effective treatment of tuberculosis requires adherence to a minimum of 6 months treatment with multiple drugs. To improve adherence and cure rates, directly observed therapy is recommended for the treatment of pulmonary tuberculosis. We compared treatment outcomes among all culture-positive patients treated for active pulmonary tuberculosis (n = 372) in San Francisco County, California from 1998 through 2000. Patients treated by directly observed therapy at the start of therapy (n = 149) had a significantly higher cure rate compared with patients treated by self-administered therapy (n = 223) (the sum of bacteriologic cure and completion of treatment, 97.8% versus 88.6%, p < 0.002), and decreased tuberculosis-related mortality (0% vs. 5.5%, p = 0.002). Rates of treatment failure, relapse, and acquired drug resistance were similar between the two groups. Forty-four percent of patients who received self-administered therapy had risk factors for nonadherence and should have been assigned to directly observed therapy. We conclude that treatment plans that emphasize directly observed therapy from the start of therapy have the greatest success in improving tuberculosis treatment outcomes.

  1. 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

  2. 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.

  3. Characterization of the discriminative stimulus properties of centrally administered (-)-DOM and LSD.

    Science.gov (United States)

    Doat, Mireille M; Rabin, Richard A; Winter, Jerrold C

    2003-02-01

    Despite the plausible assumption that the effects of hallucinogens predominantly arise in the central nervous system, most studies of these drugs in intact subjects have been conducted following systemic administration. The objective of the present investigation was to characterize the stimulus effects of (-)2,5-dimethoxy-4-methylamphetamine ((-)-DOM) following intracerebroventricular administration. Chronic indwelling cannulae were implanted into the lateral ventricle of male Fischer 344 rats trained to discriminate systemically administered (-)-DOM or lysergic acid diethylamide (LSD) from saline. Time-course and dose-response relationships for (-)-DOM and LSD administered intracerebroventricularly were established. For both LSD and (-)-DOM, central administration did not change the pretreatment times required for the maximal stimulus effects to occur. However, the onset of the stimulus effect was more rapid following intracerebroventricular administration. Following pretreatment periods that maximize drug-appropriate responding, central administration of (-)-DOM and LSD was approximately 2.4- and 1.5-times more potent, respectively, than systemic administration. The results of this study are consistent with the assumption that the stimulus effects of (-)-DOM and LSD are centrally mediated.

  4. 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.

  5. Lower gastric ulcerogenic effect of suxibuzone compared to phenylbutazone when administered orally to horses.

    Science.gov (United States)

    Monreal, L; Sabaté, D; Segura, D; Mayós, I; Homedes, J

    2004-04-01

    The objective was to compare the gastrointestinal and general toxicity of suxibuzone (SBZ) to that of phenylbutazone (PBZ) when administered orally in horses. Fifteen healthy horses were allocated to three treatment groups. One group received a high dose of PBZ for two weeks; the second group was given an equimolecular dosage of SBZ; and a third group received placebo. Horses were daily monitored, and blood samples were collected before and during the study. On day 18, complete post-mortem examinations were performed. One horse treated with PBZ showed clinical signs of NSAID toxicosis. Small oral ulcers were also detected in other two horses from the PBZ group and in two horses from the SBZ group. There were no statistical differences in the blood parameters among groups. Ulcers in the stomach's glandular mucosa were observed in all horses of the PBZ group, while only two horses of the SBZ group showed ulcerations. PBZ horses had a significant higher ulcerated area, and gastric ulcers were significantly deeper than those in the SBZ and placebo groups. No other lesions were found in any other tissue. In conclusion, SBZ causes significantly lower gastric ulcerogenic effect than PBZ when administered orally at equimolecular doses in horses.

  6. 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.

  7. 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.

  8. An Internet administered treatment program for obsessive-compulsive disorder: a feasibility study.

    Science.gov (United States)

    Wootton, Bethany M; Titov, Nickolai; Dear, Blake F; Spence, Jay; Andrews, Gavin; Johnston, Luke; Solley, Karen

    2011-12-01

    The present study evaluates efficacy of a new Internet-administered cognitive behavioral therapy (CBT) protocol, The OCD Program, designed to treat obsessive-compulsive disorder (OCD) remotely. This protocol comprises 8 online lessons delivered over 8 weeks and incorporates cognitive and behavioral techniques. Twenty-two individuals with a principal diagnosis of OCD received CBT-based online lessons, homework assignments, twice weekly contact from a clinical psychologist, and automated emails. Eighty-one percent of participants completed the lessons within the 8-week program. Post-treatment and 3-month follow-up data were collected from 21/21 (100%) and 19/21 (91%) participants, respectively. Participants improved significantly on the primary outcome measures, the Yale-Brown Obsessive Compulsive Scale and Obsessive Compulsive Inventory-Revised, with within-groups effect sizes (Cohen's d) at follow-up of 1.28 and 0.60, respectively. Participants rated the procedure as highly acceptable despite receiving an average of only 86min (SD=54.4min) telephone contact with the therapist over the 8 weeks. These results provide preliminary support for efficacy of Internet-administered treatment for obsessive-compulsive disorder. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. 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

  10. 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

  11. Safety of DTaP-IPV/Hib vaccine administered routinely to infants and toddlers.

    Science.gov (United States)

    Hansen, John; Timbol, Julius; Lewis, Ned; Pool, Vitali; Decker, Michael D; Greenberg, David P; Klein, Nicola P

    2016-07-29

    The combination DTaP-IPV/Hib vaccine was licensed in the United States in 2008 for children ages 6weeks through 4years with doses administered at 2, 4, 6, and 15-18months of age. The aim of this study was to assess the safety of DTaP-IPV/Hib vaccine routinely administered as part of clinical care to infants at Kaiser Permanente Northern California. This was an observational, retrospective study that included all 2-month-old infants vaccinated with either DTaP-IPV/Hib or another DTaP-containing vaccine. We monitored all subjects for non-elective hospitalizations, emergency department visits and selected outpatient outcomes (seizures, Guillain-Barré Syndrome, encephalopathy, encephalitis, alteration of consciousness, meningitis, hypersensitivity reactions, immune thrombocytopenic purpura, hemolytic anemia, type 1 diabetes, and Kawasaki disease) beginning with their first dose through 6months after a 4th dose or until 24months of age. We calculated incidence rate ratios (IRRs) in the primary analysis by comparing rates of outcomes during the post-vaccination risk interval with rates during a comparison interval more remote from vaccination. Secondary analyses compared outcomes after DTaP-IPV/Hib with those after other DTaP-containing vaccines. We reviewed the medical records of selected outcomes. From October 1, 2008 through July 31, 2010, 14,042 subjects received a first dose of DTaP-IPV/Hib, 13,194 received 2 doses, 12,548 received 3 doses and 6702 received 4 doses. Overall, there were 166 comparisons with significantly elevated IRRs and 165 comparisons with significantly reduced IRRs. Medical record review of outcomes with significantly elevated IRRs in both the primary and secondary analyses did not suggest any relationship with DTaP-IPV/Hib. This study did not detect any safety concerns following DTaP-IPV/Hib and provides reassurance that DTaP-IPV/Hib administered as part of routine care was not associated with unexpected safety risks. Clinical

  12. Centrally administered TNF increases arterial blood pressure independently of nitric oxide synthase.

    Science.gov (United States)

    Żera, Tymoteusz; Nowiński, Artur; Kwiatkowski, Piotr

    2016-08-01

    Emerging evidence indicates that increased levels of TNF in the brain are associated with hypertension. Nitric oxide synthase (NOS) is involved in the central control of the cardiovascular system, exerting both pro- and antihypertensive effects. TNF induces hypothalamic synthesis of nitric oxide. We checked if acutely administered TNF into the cerebral ventricles affects arterial blood pressure, heart rate and baroreflex sensitivity, and whether TNF actions are dependent on NOS in normotensive rats. We carried out hemodynamic measurements in 6 groups of freely moving, adult Sprague-Dawley male rats, intracerebroventricularly (ICV) infused with either: 1) saline (5μl/h); 2) TNF (200ng/5μl/h); 3) non-selective NO synthase inhibitor - l-NG-Nitroarginine Methyl Ester (l-NAME) (1mg/5μl/h); 4) TNF together with l-NAME (200ng and 1mg/5μl/h, respectively); 5) neuronal NO synthase inhibitor - 7-nitroindazole sodium salt (7-NI) (20μg/10μl/h); 6) or TNF together with 7-NI (200ng and 20μg/10μl/h, respectively). Mean arterial blood pressure (MABP), heart rate (HR) and spontaneous baroreflex sensitivity (sBRS) evaluated by the sequence method were analysed. ICV infusion of TNF caused a significant increase in MABP accompanied by a transient increase in HR, and a decrease in sBRS. ICV infusion of l-NAME increased MABP, but it did not change HR, nor sBRS. ICV infusion of 7-NI did not affect MABP, nor HR, nor sBRS. TNF administered together with l-NAME increased MABP with a transient increase in HR without changes of sBRS. Similarly, ICV infusion of TNF with 7-NI increased MABP without changes in HR and sBRS. Centrally administered TNF increases MABP and HR and blunts sBRS. The pressor effect of TNF appears to be independent of NOS activity in the brain. Inhibition of nNOS restores sBRS in TNF treated rats. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Phase I and pharmacokinetic study of irofulven administered weekly or biweekly in advanced solid tumor patients.

    Science.gov (United States)

    Alexandre, Jérôme; Raymond, Eric; Kaci, Mahmoud Ould; Brain, Etienne C; Lokiec, François; Kahatt, Carmen; Faivre, Sandrine; Yovine, Alejandro; Goldwasser, François; Smith, Sheri L; MacDonald, John R; Misset, Jean-Louis; Cvitkovic, Esteban

    2004-05-15

    We performed a Phase I and pharmacokinetic study to determine the maximum tolerated dose of irofulven (6-hydroxymethylacylfulvene; MGI-114, MGI PHARMA, Inc.), administered in intermittent weekly schedules in patients with advanced solid tumors. Three schedules were tested: A, days 1, 8, and 15 every 4 weeks; B, days 1 and 8 every 3 weeks; C, days 1 and 15 every 4 weeks. Drugs were administered as 5- and 30-min (schedules B and C) infusions. Dose levels of 10, 12, and 14 mg/m(2)/week were explored. Ninety-nine patients received 256 cycles. Fifteen of 74 patients evaluable for maximum tolerated dose experienced 16 dose-limiting toxicities (5 of 17 patients on schedule A, 2 of 25 on schedule B, and 8 of 32 on schedule C), principally treatment delay for thrombocytopenia. Schedule A was considered unsuitable because of frequent thrombocytopenia and treatment discontinuations. Twenty-three percent of the overall population (22 patients with grade 1-2, and 1 patient with grade 3), including 37% of patients on dose level 3, experienced unexpected dose-limiting visual toxicity, which included color perception and visual field alterations linked to retinal cone cell toxicity; the visual toxicity had an early onset, was mostly reversible, and was related to higher dose per infusion. Safety profiles were similar for 5- and 30-min infusions. The relationships between dose and area under the plasma concentration-time curve and maximum plasma concentration were linear for both 5- and 30-min infusions in the 78 patients evaluated for pharmacokinetics. The area under the plasma concentration-time curve and clearance were comparable between infusion durations. Responses included one complete (ovarian), one partial (renal), and seven disease stabilizations lasting >4 months. We recommend doses of 18 mg/m(2)/infusion for schedule B and 24 mg/m(2)/infusion for schedule C, limited to 0.55 mg/kg and a total dose of 50 mg/infusion, administered over 30-min.

  14. Computer Administered Safety Planning for Individuals at Risk for Suicide: Development and Usability Testing.

    Science.gov (United States)

    Boudreaux, Edwin D; Brown, Gregory K; Stanley, Barbara; Sadasivam, Rajani S; Camargo, Carlos A; Miller, Ivan W

    2017-05-15

    Safety planning is a brief intervention that has become an accepted practice in many clinical settings to help prevent suicide. Even though it is quick compared to other approaches, it frequently requires 20 min or more to complete, which can impede adoption. A self-administered, Web-based safety planning application could potentially reduce clinician time, help promote standardization and quality, and provide enhanced ability to share the created plan. The aim of this study was to design, build, and test the usability of a Web-based, self-administered safety planning application. We employed a user-centered software design strategy led by a multidisciplinary team. The application was tested for usability with a target sample of suicidal patients. Detailed observations, structured usability ratings, and Think Aloud procedures were used. Suicidal ideation intensity and perceived ability to cope were assessed pre-post engagement with the Web application. A total of 30 participants were enrolled. Usability ratings were generally strong, and all patients successfully built a safety plan. However, the completeness of the safety plan varied. The mean number of steps completed was 5.5 (SD 0.9) out of 6, with 90% (27/30) of participants completing at least 5 steps and 67% (20/30) completing all 6 steps. Some safety planning steps were viewed as inapplicable to some individuals. Some confusion in instructions led to modifications to improve understandability of each step. Ratings of suicide intensity after completion of the application were significantly lower than preratings, pre: mean 5.11 (SD 2.9) versus post: mean 4.46 (SD 3.0), t27=2.49, P=.02. Ratings of ability to cope with suicidal thoughts after completion of the application were higher than preratings, with the difference approaching statistical significance, pre: mean 5.93 (SD 2.9), post: mean 6.64 (SD 2.4), t27=-2.03, P=.05. We have taken the first step toward identifying the components needed to maximize

  15. Metabolism of sialic acids from exogenously administered sialyllactose and mucin in mouse and rat.

    Science.gov (United States)

    Nöhle, U; Schauer, R

    1984-12-01

    A mixture of N-acetyl-[4,5,6,7,8,9-14C]neuraminosyl-alpha (2-3(6]-galactosyl-beta (1-4-glucose[( 14C]sialyl-lactose) and N-acetylneuraminosyl-alpha (2-3(6]-galactosyl-beta(1-4)-glucit-1-[3H]ol(sialyl-[3H]lactitol) as well as porcine submandibular gland mucin labeled with N-acetyl- and N-glycoloyl-[9-(3)H]neuraminic acid were administered orally to mice. The distribution of the different isotopes was followed in blood, tissues and excretion products of the animals. One half of the [14C]sialyl-lactose/sialyl-[3H]lactitol mixture given orally was excreted unchanged in the urine. The other half was hydrolysed by sialidase and partly metabolized further, followed by the excretion of 30% of the 14C-radioactivity as free N-acetyl-[4,5,6,7,8,9-14C]neuraminic acid and 60% of this radioactivity in the form of non-anionic compounds including expired 14CO2 within 24 h. The 14C-radioactivity derived from the [14C]sialyl-lactose/sialyl-[3H]lactitol mixture which remained in the bodies of fasted mice after 24 h was less than 1%. In the case of well-fed mice, a higher amount of the sialic acid residues was metabolized. The bulk of radioactivity of the mucin was resorbed within 24 h. About 40% of the radioactivity administered was excreted by the urine within 48 h; 30% of this radioactivity represented sialic acid and 70% other anionic and non-anionic metabolic products. 60% of the radioactivity administered remained in the body, and bound 3H-labeled sialic acids were isolated from liver. Sialyl-alpha (2-3)-[3H]lactitol was injected intravenously into rats; the substance was rapidly excreted in the urine without decomposition. These studies show that part of the sialic acids bound to oligosaccharides and glycoproteins can be hydrolysed in intestine by sialidase and be resorbed. This is followed either by excretion as free sialic acid or by metabolization at variable degrees, which apparently depends on the compound fed and on the retention time in the digestive tract.

  16. Methoxyflurane and nitrous oxide as obstetric analgesics. II. A comparison by self-administered intermittent inhalation.

    Science.gov (United States)

    Jones, P L; Rosen, M; Mushin, W W; Jones, E V

    1969-08-02

    Methoxyflurane (0.35%) in air and nitrous oxide/oxygen (50%/50%) self-administered intermittently in the usual way have been compared as analgesics for labour. There were 25 patients in each group. Objective assessment by an anaesthetist showed that methoxyflurane is the more effective analgesic, and this was supported by the opinion of the multiparae. Nausea and vomiting were significantly less with methoxyflurane. Fifty per cent. nitrous oxide in oxygen given intermittently does not appear to be the best analgesic concentration. Nevertheless, since a considerable variation in sensitivity exists, it would probably be unwise to consider the introduction of higher concentrations for use by unsupervised midwives.This trial confirms the predictions made by us using a method for screening inhalational analgesics, in which methoxyflurane and nitrous oxide were given continuously.

  17. External radiation doses from patients administered with radiopharmaceuticals measurements and Monte Carlo simulation

    Directory of Open Access Journals (Sweden)

    Kinsara Abdul Raheem

    2014-01-01

    Full Text Available Monte Carlo simulations and dose measurements were performed for radionuclides in the whole body and trunks of different sizes in order to estimate external radiation whole body doses from patients administered with radiopharmaceuticals. Calculations were performed on cylindrical water phantoms whose height was 176 cm and for three body diameters: of 24 cm, 30 cm, and 36 cm. The investigated radionuclides were: 99mTc, 131I, 23I, 67Ga, 201Tl, and 111In. Measured and MCNP-calculated values were 2-6 times lower than the values calculated by the point source method. Additionaly, the total dose received by the public until a radionuclide is completely disintegrated was calculated. The other purpose of this work is to provide data on whole body and finger occupational doses received by technologists working in nuclear medicine. Data showed a wide variation in doses that depended on the individual technologist and the position of the dosimeter.

  18. (Ad)ministering love: providing family foster care to infants with prenatal substance exposure.

    Science.gov (United States)

    Marcellus, Lenora

    2008-09-01

    A significant percentage of children in foster care in North America are younger than 1 year of age and are in foster care because of parental substance use and other social challenges. Infants might present with specific health and behavioral issues that are challenging to manage within the foster family home environment; foster families require specialized skills and knowledge to manage these issues. In this article, the author describes a constructivist grounded theory of the process of becoming and providing family foster caregiving in the context of caring for infants with prenatal alcohol and/or drug exposure. The basic social process of (ad)ministering love was identified. The author further describes the three phases of this process and the core concepts within each phase.

  19. Biodistribution of Intraperitoneally-administered {sup 125}I-labeled IgG in Mouse

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sooyong; Dho, So Hee; Cho, Eunha; Lee, Soyoung; Jung, Sunghee; Lim, Jaecheong [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-10-15

    The use of radiolabeled antibodies is one of the most effective strategies to diagnose and treat cancers. However, it is hindered by the relatively low delivery to tumors following intravenous administration, in particular, cancers in peritoneal cavity. Intraperitoneal administration of radiolabeled antibodies results in significantly higher exposure to the peritoneal cavity than does intravenous administration. Therefore, intraperitoneal administration of the radiolabeled antibodies can be more effective to diagnose and treat cancers in peritoneal cavity such as ovarian and colonic cancers. This study was performed to determine the biodistribution pattern of intraperitoneally-administered radiolabeled antibodies. The {sup 125}I-labeled IgG was rapidly absorbed into the blood and organs, and the radioactivities were dropped in 24 hr p.i. These results suggest that the intraperitoneal administration of the radiolabeled antibodies can be an effective way to treat diseases in the peritoneal cavity.

  20. The reliability of the Alcohol Timeline Followback when administered by telephone and by computer.

    Science.gov (United States)

    Sobell, L C; Brown, J; Leo, G I; Sobell, M B

    1996-09-01

    The Alcohol Timeline Followback (TLFB) has been shown to be a psychometrically sound assessment instrument for obtaining retrospective daily estimates of alcohol consumption. These evaluations, however, have been limited to face-to-face paper-and-pencil interviews. As use of the TLFB method has increased, investigators have reported using the method to collect follow-up data by telephone. Also, as with many assessment instruments, a computerized version of the TLFB method has been developed. The psychometric characteristics of the TLFB method under these administration conditions have not been evaluated. This paper presents results from two studies showing that the Alcohol TLFB method can obtain reliable drinking data when administered over the telephone and by computer.

  1. 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.

  2. Low reliability of sighted-normed verbal assessment scores when administered to children with visual impairments.

    Science.gov (United States)

    Morash, Valerie S; McKerracher, Amanda

    2017-03-01

    The most common and advocated assessment approach when a child cannot access visual materials is to use the verbal subscales of a test the psychologist already has and is familiar with. However, previous research indicates that children with visual impairments experience atypical verbal development. This raises the question of whether verbal subscale scores retain their reliability and interpretation validity when given to children with visual impairments. To answer this question, we administered a vocabulary subscale from a common intelligence test along with several nonverbal subscales to 15 early-blind adolescents (onset of ≤2 years). Reliability of only the vocabulary test scores was insufficient for high-stakes testing. This finding points to the broader issue of difficulties in assessing populations of exceptional children who experience atypical development trajectories, possibly making their assessment with common tests inappropriate. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  3. The antinociceptive efficacy of buprenorphine administered through the drinking water of rats

    DEFF Research Database (Denmark)

    Jessen, L; Bjerrum, Ole Jannik; Christensen, Sten

    2007-01-01

    such as administration of analgesics in the drinking water would be desirable. However, the efficacy of a chronic oral analgesic treatment via this route has not yet been documented. This study investigated the antinociceptive efficacy of buprenorphine administered ad libitum via the drinking water of laboratory rats....... The antinociceptive efficacy of buprenorphine in drinking water was compared with repeated subcutaneous injections. A comparison was also made between buprenorphine in drinking water and the combination of one single subcutaneous injection of buprenorphine followed by buprenorphine in drinking water. Antinociception...... was assessed by use of an analgesiometric model measuring the rats' latency time to withdrawal from a noxious heat stimulus applied to the plantar surface of the paw. Results revealed that buprenorphine in drinking water (0.056 mg/mL) induced significant increases in paw withdrawal latency times during a three...

  4. Cytomegalovirus-associated esophageal ulcer in an immunocompetent infant: When should ganciclovir be administered?

    Directory of Open Access Journals (Sweden)

    Hyo-Jeong Jang

    2012-12-01

    Full Text Available Cytomegalovirus (CMV-associated esophageal ulcer is rare in immunocompetent infants. The presence of inclusion bodies and immunohistochemical staining for CMV in biopsy specimens obtained during esophagogastroduodenoscopy (EGD indicate that such ulcers occur because of CMV infection. A 7-week-old female infant who experienced frequent vomiting and feeding intolerance was diagnosed with a massive CMV-associated ulcer in the distal esophagus. The ulcer improved after conservative treatment using proton-pump inhibitors; however, ganciclovir was not administered. In a follow-up EGD biopsy specimen, no CMV inclusion bodies were present, and immunohistochemical staining results for this virus were negative. The presence of CMV inclusion bodies indicates active viral replication. If persistent inclusion bodies or positive immunohistochemical staining for CMV is observed in follow-up biopsy specimens, ganciclovir may be used to treat CMV-associated esophageal ulcers.

  5. Aripiprazole blocks acute self-administration of cocaine and is not self-administered in mice

    DEFF Research Database (Denmark)

    Sørensen, Gunnar; Sager, Thomas N; Petersen, Jørgen H

    2008-01-01

    doses (0.03, 0.1, and 0.3 mg/kg/infusion) even caused significant decreases in nose-poking activity, possibly due to extrapyramidal side effects. CONCLUSIONS: These data are consistent with a potential role for aripiprazole in treatment of cocaine addiction without abuse potential per se.......RATIONALE: The novel antipsychotic aripiprazole in use for treatment of schizophrenia is a partial agonist at dopamine D(2) receptors with actions at a variety of other receptors as well. Cocaine is believed to exert an important part of its rewarding effect by increasing extracellular levels...... of dopamine that subsequently act at dopamine D(2) receptors. OBJECTIVES: As a partial agonist, aripiprazole may antagonize effects at D(2) receptors and we accordingly tested whether aripiprazole could antagonize self-administration of cocaine. Because D(2)-like receptor agonists are self-administered, a D(2...

  6. 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...... 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......), 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...

  7. Saved by the Nose: Bystander-Administered Intranasal Naloxone Hydrochloride for Opioid Overdose

    Science.gov (United States)

    Doe-Simkins, Maya; Epstein, Andy; Moyer, Peter

    2009-01-01

    Administering naloxone hydrochloride (naloxone) during an opioid overdose reverses the overdose and can prevent death. Although typically delivered via intramuscular or intravenous injection, naloxone may be delivered via intranasal spray device. In August 2006, the Boston Public Health Commission passed a public health regulation that authorized an opioid overdose prevention program that included intranasal naloxone education and distribution of the spray to potential bystanders. Participants were taught by trained nonmedical needle exchange staff. After 15 months, the program provided training and intranasal naloxone to 385 participants who reported 74 successful overdose reversals. Problems with intranasal naloxone were uncommon. Overdose prevention education with distribution of intranasal naloxone is a feasible public health intervention to address opioid overdose. PMID:19363214

  8. Evaluation of the impact of orally administered carbohydrates on postprandial blood glucose levels in different pre-clinical models

    OpenAIRE

    Marques,Any de Castro Ruiz; Schiavon,Fabiana Percinoto Monteiro; Travassos,Patricia Batista; Eik,Vanessa Fontana; Godoy,Guilherme; Schamber,Christiano Rodrigues; Bazotte,Roberto Barbosa

    2016-01-01

    ABSTRACT We developed a pre-clinical model in which to evaluate the impact of orally administered carbohydrates on postprandial blood glucose levels. For this purpose, we compared the effects of different carbohydrates with well-established glycemic indexes. We orally administered (gavage) increasing amounts (0.2, 0.4, 0.6, 0.8, and 1.0 g/kg) of sucrose and lactose to rats which had been fasted for 6 h or 15 h, respectively. In part of the experiments we administered frutose (gavagem). Three ...

  9. 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.

  10. The efficacy of a volunteer-administered cognitive stimulation program in long-term care homes.

    Science.gov (United States)

    van Zon, Lorraine; Kirby, John R; Anderson, Nicole

    2016-06-01

    Cognitive impairment (CI) that arises in some older adults limits independence and decreases quality of life. Cognitive stimulation programs delivered by professional therapists have been shown to help maintain cognitive abilities, but the costs of such programming are prohibitive. The present study explored the feasibility and efficacy of using long-term care homes' volunteers to administer a cognitive stimulation program to residents. Thirty-six resident participants and 16 volunteers were alternately assigned to one of two parallel groups: a control group (CG) or stimulation group (SG). For eight weeks, three times each week, CG participants met for standard "friendly visits" (casual conversation between a resident and volunteer) and SG participants met to work through a variety of exercises to stimulate residents' reasoning, attention, and memory abilities. Resident participants were pre- and post-tested using the Weschler Abbreviated Scale of Intelligence-Second Edition, Test of Memory, and Learning-Senior Edition, a modified Letter Sorting test (LS), Clock Drawing Test (CDT), and the Action Word Verbal Fluency Test. Two-way analyses of covariance (ANCOVA) controlling for dementia diagnosis indicated statistically greater improvements in the stimulation participants than in the control participants in Immediate Verbal Memory, p = 0.011; Non-Verbal Memory, p = 0.012; Learning, p = 0.016; and Verbal Fluency, p = 0.024. The feasibility and efficiency of a volunteer-administered cognitive stimulation program was demonstrated. Longitudinal studies with larger sample sizes are recommended in order to continue investigating the breadth and depth volunteer roles in the maintenance of the cognitive abilities of older adults.

  11. Evaluation of the effect of orally administered acid suppressants on intragastric pH in cats.

    Science.gov (United States)

    Parkinson, S; Tolbert, K; Messenger, K; Odunayo, A; Brand, M; Davidson, G; Peters, E; Reed, A; Papich, M G

    2015-01-01

    Acid suppressant drugs are a mainstay of treatment for cats with gastrointestinal erosion and ulceration. However, clinical studies have not been performed to compare the efficacy of commonly PO administered acid suppressants in cats. To compare the effect of PO administered famotidine, fractionated omeprazole tablet (fOT), and omeprazole reformulated paste (ORP) on intragastric pH in cats. We hypothesized that both omeprazole formulations would be superior to famotidine and placebo. Six healthy adult DSH colony cats. Utilizing a randomized, 4-way crossover design, cats received 0.88-1.26 mg/kg PO q12h fOT, ORP, famotidine, and placebo (lactose capsules). Intragastric pH monitoring was used to continuously record intragastric pH for 96 hours beginning on day 4 of treatment. Plasma omeprazole concentrations at steady state (day 7) were determined by high performance liquid chromatography (HPLC) with ultraviolet detection. Mean percentage time that intragastric pH was ≥ 3 and ≥ 4 were compared among groups using ANOVA with a posthoc Tukey-Kramer test (α = 0.05). The mean percentage time ± SD that intragastric pH was ≥ 3 was 68.4 ± 35.0% for fOT, 73.9 ± 23.2% for ORP, 42.8 ± 18.6% for famotidine, and 16.0 ± 14.2% for placebo. Mean ± SD plasma omeprazole concentrations were similar in cats receiving fOT compared to those receiving ORP and in a range associated with acid suppression reported in other studies. These results suggest that both omeprazole formulations provide superior acid suppression in cats compared to famotidine or placebo. Fractionated enteric-coated OT is an effective acid suppressant despite disruption of the enteric coating. Copyright © 2014 by the American College of Veterinary Internal Medicine.

  12. Musical Rehabilitation in Adult Cochlear Implant Recipients With a Self-administered Software.

    Science.gov (United States)

    Smith, Leah; Bartel, Lee; Joglekar, Samidha; Chen, Joseph

    2017-09-01

    The goal of this study was to determine if a self-administered computer-based rehabilitation program could improve music appreciation and speech understanding in adults who have a cochlear implant (CI). Prospective study. Tertiary adult CI program. Twenty-one postlingually deafened cochlear implant users between the ages of 27 and 79 years were recruited. A self-administered music rehabilitative software was designed to help improve the perception of musical patterns of increasing complexity, as well as pitch and timbre perception, premised on focused and divided attention. All participants completed a diagnostic music test before and after rehabilitative training, including tests of pitch and timbre perception and pattern identification with increasing levels of difficulty. Speech data in quiet and noise was also collected both pre- and post-training. Participants trained for a minimum of 3.5 hours a week, for 4 weeks. Mean changes in music perception and enjoyment as well as speech perception (IEEE sentence test in quiet and noise). Post-training diagnostic test scores, as compared with pretraining scores, indicated significant improvements in musical pattern perception. Tests of speech perception in quiet and in noise were significantly improved in a subset of this cohort. All of the training participants thought that the training helped to improve their recognition skills, and found the program to be beneficial. Despite the limitations of current CI technology, the results of this study suggest that auditory training can improve music perception skills, and possibly speech intelligibility, lending further support to rehabilitation being an integral part of the postimplantation paradigm.

  13. Testing the Question-Behavior Effect of Self-Administered Surveys Measuring Youth Drug Use.

    Science.gov (United States)

    Briney, John S; Brown, Eric C; Kuklinski, Margaret R; Oesterle, Sabrina; Hawkins, J David

    2017-09-29

    Concern that asking about a specific behavior could elicit that behavior is often cited as a reason that communities and schools should not administer surveys about youth drug use. In this study, we investigated if this question-behavior effect exists related to substance use. We examined if simply asking a student about their current drug use leads to an increase in drug use 1 year later. This study tests the validity of the question-behavior effect on youth drug use in a longitudinal panel of 2,002 elementary school students. The sample of students was drawn from the Community Youth Development Study, a community-randomized test of the Communities That Care prevention system. If the prevalence of self-reported drug use in sixth grade in a sample surveyed in fifth and sixth grades was higher than in an accretion sample surveyed only in sixth grade, the difference could indicate a question-behavior effect. Results from logistic regression analyses did not provide any evidence of a question-behavior effect on 30-day or lifetime prevalence of alcohol, tobacco, inhalant, or marijuana use reported in sixth grade. Asking youth about drug use in a survey did not increase the rates of self-reported drug use measured 1 year later. The absence of evidence of a question-behavior effect should ease concerns of communities and schools when administering surveys asking youth about their drug use. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  14. 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.

  15. 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.

  16. 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.

  17. Effects of orally administered bovine lactoferrin on the immune system of healthy volunteers.

    Science.gov (United States)

    Yamauchi, K; Wakabayashi, H; Hashimoto, S; Teraguchi, S; Hayasawa, H; Tomita, M

    1998-01-01

    A protective effect of bovine lactoferrin (Lf) during lethal bacteraemia has been reported in mice. Also, protective effects of orally administered bovine Lf have been reported in cases of intractable stomatitis in cats and Cryptocaryon irritans infection in red sea bream. In this study, we examined the effects of orally administered bovine Lf on the immune system of healthy volunteers. Ten healthy male volunteers (age range of 31 to 55 years old) were given bovine Lf (2 g/body/day) for 4 weeks. Blood samples were drawn before, during and after administration of Lf. Phagocytic activity and superoxide production activity of polymorphonuclear leukocytes (PMN) were evaluated from the number of PMN phagocytizing polymer particles and by the dichlorofluorescein (DCFH) oxidation assay, respectively. The expression levels of CD11b, CD16 and CD56 molecules on leukocytes were quantified using flow cytometry. The phagocytic activity of PMN increased during the period of Lf administration in 3 of the 10 volunteers. In 2 of the 3 volunteers in which the phagocytic activity increased, PMN expressed CD16 at higher levels corresponding to the increase in 3 of the 10 volunteers, whereas the CD11b+ lymphocytes and CD56+ lymphocytes increased in 4 volunteers including the same 3 volunteers who showed an increase in CD16+. These results suggest that the proportion of natural killer (NK) cells among the lymphocytes might have increased in these subjects. It was demonstrated that the phagocytic activity or superoxide production activity of PMN or the proportions of CD11b+, CD16+ and CD56+ in lymphocytes was influenced by Lf administration in 7 of the 10 volunteers, while the effects of Lf on the immune system differed in individual cases. These results suggest that Lf administration may influence primary activation of the host defense system.

  18. The problem of the iridal prolapse during the cataract surgery in patients administering the Tamsulosin

    Directory of Open Access Journals (Sweden)

    Jovanović Miloš

    2011-01-01

    Full Text Available Introduction: Tamsulosin is alfa 1a-adrenergic antagonist administered to patients with prostatic hypertrophy. It causes the relaxation of the smooth muscles of prostate and urinary bladder and results in symptom alleviation. However, Tamsulosin side effect reflects in the atony of pupil's dilatory muscle, and accordingly, the iris during the phacoemulsification becomes folded and prolapses through the phacoemulsification incision. Moreover, there is no possibility of sufficient pupil dilatation because of the predominating effect of the pupillary m. sphincteris. In order to manage the iridal prolapse during the surgery, a special high-cohesive visco-elastic as well as multi-positioned iridal retractors are being used. Case report: This is a case report of three patients. Common to all of them was that they were all males in the advanced age, had benign prostatic hypertrophy, received Tamsulosin and underwent cataract surgery by phacoemulsification. In all three patients, adequately dilated pupils required for unobstructed performance of phacoemulsification could not be achieved by regular medicaments. In addition, in all three cases, the iris prolapsed through the incision during the surgical intervention. Upon applying the viscoelastic and deepening of the anterior ocular chamber as well as after the placement of iridal retractors in different positions, the operation was successfully brought to an end. Conclusion: In patients administering the Tamsulosin, cataract phacoemulsification is more frequently associated with complications. A special problem is a constant iridal prolapse through the incision. Unfortunately, no so far described method for managing this problem has been fully successful, what was confirmed in our case reports as well. Therefore, the operation for cataract in these patients should be carried out only by most experienced and skillful surgeons.

  19. 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.

  20. The effect of orally administered epigallocatechin-3-gallate on ligature-induced periodontitis in rats.

    Science.gov (United States)

    Cho, A-R; Kim, J-H; Lee, D-E; Lee, J-S; Jung, U-W; Bak, E-J; Yoo, Y-J; Chung, W-G; Choi, S-H

    2013-12-01

    Epigallocatechin-3-gallate (EGCG) is known for its beneficial properties, including anti-inflammatory and anti-oxidative activities. Recently, reports have suggested that EGCG plays a pivotal role in regulating cytokine expression and osteoclastic activity. In the present study, we investigated whether orally administered EGCG has a therapeutic effect on ligature-induced periodontitis. Forty-eight Sprague-Dawley rats were treated with EGCG or phosphate-buffered saline. Periodontitis was induced by tying a ligature for 7 d. After removing ligation, EGCG (200 mg/kg) or phosphate-buffered saline was administered via oral gavage on a daily basis. Rats were killed after 1, 2 and 4 wk of administration. Histologic and histomorphometric analyses, tartrate resistant acid phosphatase staining and immunohistochemistry were carried out. In the control group, bone loss did not recover even after the causative factor of periodontitis was eliminated. On the other hand, distance from cemento-enamel junction to alveolar bone crest, long junctional epithelium and collagen destruction were reduced in the EGCG group. Decreased interleukin (IL)-6 expression was shown from the early stage of EGCG administration, followed by reduced tumor necrosis factor (TNF) expression at week 4 EGCG group. The CT area showed a higher decrease of IL-6 expression between the control and EGCG group than alveolar bone area. Downregulation of TNF and IL-6 expression led to a decrease in osteoclast number and activity, which resulted in reduced bone loss. Systemic administration of EGCG could have a therapeutic effect on damaged periodontal tissue. Inhibited cytokine expression, including TNF and IL-6 is responsible for the reduction in osteoclast formation, osteoclastic activity and collagen destruction. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Rectally administered diclofenac (Voltaren) reduces vomiting compared with opioid (morphine) after strabismus surgery in children.

    Science.gov (United States)

    Wennström, B; Reinsfelt, B

    2002-04-01

    Nausea, vomiting and pain are common complications after strabismus surgery in children. Diclofenac, a non-steroid anti-inflammatory drug, is widely used to treat acute and chronic pain but there are few reports of its use given rectally in children undergoing strabismus surgery. This open randomised study was designed to investigate the analgesic and anti-emetic properties of rectally administered diclofenac compared with opioid (morphine) given i.v. in connection with strabismus surgery in children. After obtaining approval from the local ethics committee and written informed consent from the parents, 50 ASA class I-II children, 4-16 years of age, were randomised to receive either rectally administered diclofenac (Voltaren) 1 mg/kg or i.v. opioid (morphine) 0.05 mg/kg perioperatively. The children were consecutively operated upon from May 1999 to January 2001. Anaesthesia was induced with fentanyl and propofol and maintained with propofol. Nitrous oxide was omitted. The postoperative pain was assessed after arrival at the post anaesthesia care unit (PACU) by using the validated Wong and Baker scale (FACES) Pain Rating Scale. Postoperative nausea and vomiting (PONV) was assessed by measuring the frequency of vomiting and the degree of nausea. In the diclofenac group the incidence of PONV during the first 24 h was 12% (of which one child had severe vomiting). The incidence of PONV was much higher, 72% (P = 0.0000), in the morphine group, where 56% of the children also had severe vomiting. There were no difference in pain score between the two groups. Recovery time at the PACU was longer (P < 0.002) and the postoperative analgesic requirement higher in the morphine group (10 vs. 5 children). No children needed overnight admission to the hospital. Diclofenac given rectally is an effective analgesic for this kind of surgery and gives less postoperative nausea than i.v. morphine. No serious adverse events were observed.

  2. Lactobacillus GG administered in oral rehydration solution to children with acute diarrhea: a multicenter European trial.

    Science.gov (United States)

    Guandalini, S; Pensabene, L; Zikri, M A; Dias, J A; Casali, L G; Hoekstra, H; Kolacek, S; Massar, K; Micetic-Turk, D; Papadopoulou, A; de Sousa, J S; Sandhu, B; Szajewska, H; Weizman, Z

    2000-01-01

    The probiotic Lactobacillus GG is effective in promoting a more rapid recovery of acute, watery diarrhea in children with rotavirus enteritis. Very limited information is available, however, on the potential role of such agents in non-rotaviral diarrheal episodes. Furthermore, no evidence is available concerning the efficacy of Lactobacillus GG administered in the oral rehydration solution during oral rehydration therapy. A multicenter trial was conducted to evaluate the efficacy of Lactobacillus GG administered in the oral rehydration solution to patients with acute-onset diarrhea of all causes. Children 1 month to 3 years of age with acute-onset diarrhea were enrolled in a double-blind, placebo-controlled investigation. Patients were randomly allocated to group A, receiving oral rehydration solution plus placebo, or group B, receiving the same preparation but with a live preparation of Lactobacillus GG (at least 10(10) CFU/250 ml). After rehydration in the first 4 to 6 hours, patients were offered their usual feedings plus free access to the same solution until diarrhea stopped. One hundred forty children were enrolled in group A, and 147 in group B. There were no differences at admission between the groups in age, sex, previous types of feeding, previous duration of diarrhea, use of antibiotics, weight, height, weight-height percentile, prevalence of fever, overall status, degree of dehydration, and percentage of in- versus outpatients. Duration of diarrhea after enrollment was 71.9 +/- 35.8 hours in group A versus 58.3 +/- 27.6 hours in group B (mean +/- SD; P = 0.03). In rotavirus-positive children, diarrhea lasted 76.6 +/- 41.6 hours in group A versus 56.2 +/- 16.9 hours in groups B (P children with acute diarrhea is safe and results in shorter duration of diarrhea, less chance of a protracted course, and faster discharge from the hospital.

  3. Coccidiosis control by administering toltrazuril in the drinking water for a 2-day period.

    Science.gov (United States)

    Mathis, G F; Froyman, R; Kennedy, T

    2004-05-07

    A 56-day floor pen study was conducted to determine the appropriate time to administer toltrazuril (Baycox) (TOL) for control of coccidiosis in broiler chickens. Litter was seeded with field strains of Eimeria acervulina, Eimeria maxima and Eimeria tenella. On Days 0, 21, 35 and 56, all birds and feed were weighed. Starting on Day 14, weekly lesion scores and oocyst counts were performed. The treatments were 125 ppm nicarb (NIC) in the starter to 66 ppm salinomycin (SAL) in the grower with no TOL (NIC/SAL/no TOL), 66 ppm salinomycin in both the starter and the grower but no TOL (SAL/SAL/no TOL), or no in-feed medication with the following TOL treatment: TOL Days 2-3, TOL Days 6-7, TOL Days 10-11, TOL Days 14-15, TOL Days 18-19, and as control NM/NM/no TOL (NM). The withdrawal feed was nonmedicated. TOL was administered in the drinking water at the rate of 7 mg/kg body weight. Oocysts per gram litter and lesion scores showed a significant infection in the NM birds, which peaked about Day 21. The NIC/SAL gave excellent early protection but only moderate protection during the SAL phase. The final performance for the SAL/SAL was significantly less compared to all TOL and NIC/SAL birds. All TOL treatments but Days 2-3 provided good coccidiosis control with accompanying performance. The absence of clinical coccidiosis relapse during the last third of the growout along with moderate oocyst counts and low lesions was indicative of unimpaired coccidiosis immunity. It can be inferred from the overall results that the use of TOL as the sole anticoccidial for two consecutive days in the drinking water between Days 10 and 14 would be the best time for good coccidiosis control allowing full performance. Copyright 2004 Elsevier B.V.

  4. Impact of allergic rhinitis and its treatment on the pharmacokinetics of nasally administered fentanyl.

    Science.gov (United States)

    Perelman, Michael; Fisher, Anthony N; Smith, Alan; Knight, Alastair

    2013-05-01

    Fentanyl pectin nasal spray (FPNS, Lazanda® in the US and PecFent® in Europe and Australia) is a novel analgesic approved for the management of breakthrough pain in cancer patients. Given that the fentanyl is nasally administered, it is important to understand whether concomitant allergic rhinitis, or its treatment with a vasoconstrictor, would affect its absorption and, potentially, its efficacy or safety. Subjects with a history of allergic rhinitis were screened to identify subjects who developed at least moderate rhinitis symptoms on exposure to pollen allergen (either ragweed or tree) in an environmental exposure chamber (EEC). These were entered into a randomized, three-way crossover study in which each subject received 100 μg of FPNS under three exposure conditions; Control (no rhinitis), Rhinitis (symptomatic without decongestant), Treated (symptomatic with concomitant oxymetazoline). Blood samples for fentanyl were collected over a 24-hour period. A total of 132 subjects was screened to identify 54 for inclusion in the study; 31 were evaluable for pharmacokinetics. Measures of fentanyl absorption (mean or median) were similar between Control and Rhinitis conditions: Cmax 453.0 vs. 467.8 pg/ml; AUCt 1,292.3 vs. 1,325.4 pg×h/ml, AUC0-∞ 1,430.6 vs. 1,387 pg×h/ml and tmax 20 vs. 17 minutes. When oxymetazoline was co-administered, overall fentanyl absorption was slightly reduced (AUC0-∞ 1,362.4 pg×h/ml); but, more clinically relevant were the delayed rate of absorption (tmax 53 minutes) and reduced Cmax (235.3 pg/ml). Patients treated with FPNS will be unaffected by the development of allergic rhinitis; but, if oxymetazoline is prescribed, the patient would benefit from added supervision when oxymetazoline is started and stopped.

  5. The effects of vitamin B6 on lens antioxidant system in valproic acid-administered rats.

    Science.gov (United States)

    Tunali, S

    2014-06-01

    Valproic acid (VPA, 2-propyl pentanoic acid) is a broad-spectrum antiepileptic drug (AED) and is commonly used in the treatment of bipolar disorders and epilepsy. AEDs are known to result in vascular disturbances. Vitamin B6 (Vit B6) is water soluble vitamin essential for normal growth, development, and metabolism. In this study, we aimed to investigate the protective effects of Vit B6 against VPA-induced lens damage in experimental animals. In this study, male 4-month-old, Sprague-Dawley rats were used. The animals were divided into four groups. Group I was intact control animals. Group II rats were administered with Vit B6 (50 mg/kg/day) for 7 days. Group III rats were administered with only VPA (500 mg/kg/day) for 7 days. Group IV was given VPA + Vit B6 (in a same dose and time). Vit B6 was given to rats by gavage and VPA was given by intraperitoneally. On the 8th day of experiment, all of the animals were fasted overnight and then killed under ether anesthesia. Lens tissues were taken from animals, homogenized in 0.9% saline to make up a 10% homogenate. The homogenates was used for glutathione (GSH), lipid peroxidation (LPO), protein levels, and enzyme analysis. In VPA groups, levels of lens GSH and LPO and activities of glutathione-S-transferase, glutathione peroxidase, glutathione reductase, and aldose reductase were increased, while superoxide dismutase activity was decreased. Treatment with Vit B6 reversed these effects. These results demonstrated that administration of Vit B6 is potentially beneficial agent to reduce the lens damage in VPA toxicity, probably by decreasing oxidative stress. © The Author(s) 2014.

  6. The effects of caffeine administered at different temperatures on foetal development.

    Science.gov (United States)

    Tomaszewski, Marek; Burdan, Franciszek; Olchowik, Grażyna; Tomaszewska, Monika

    2016-01-01

    An easy access to products containing caffeine makes it widely consumed to excess by the general population, including pregnant women. Beverages containing caffeine are consumed at different temperatures (iced, hot, room temperature). Caffeine easily passes through biological membranes, including the blood-brain barrier, the placental barrier, and can also enter the amniotic fluid, breast milk and semen. The aim of this study was to evaluate the relationship between caffeine's developmental toxicity, and the solution's temperature (both low and high) administered to pregnant female rats. Fertilized females were randomly divided into two main groups: an experimental (E) and a control group (C). The experimental groups received caffeine (30mg/day) in 10 (E1), 25 (E2) and 45(o)C (E3). The females in the control group were given water at the same temperature (C1, C2 and C3). On the day 21 of pregnancy, the pregnant females were killed by decapitation, using a specially prepared laboratory guillotine, after which the mothers' internal organs were weighed. Additionally, the offspring were examined using standard teratological methods. The study found that caffeine administered to pregnant females at a dose of 30mg/day and at the temperatures of 10°C, 25°C or 45°C did not produce any teratogenic effects. The only sign of its adverse effect was the appearance of developmental abnormalities in the form of haematomas and saturated bleeding in the internal organs. These changes most frequently occurred in foetuses of females which received caffeine at 10°C or 45°C.

  7. Pharmacokinetics of meloxicam administered orally to rabbits (Oryctolagus cuniculus) for 29 days.

    Science.gov (United States)

    Delk, Katie W; Carpenter, James W; KuKanich, Butch; Nietfeld, Jerome C; Kohles, Micah

    2014-02-01

    To determine the pharmacokinetics and safety of meloxicam in rabbits when administered orally for 29 days. 6 healthy rabbits. Meloxicam (1.0 mg/kg, PO, q 24 h) was administered to rabbits for 29 days. Blood was collected immediately before (time 0) and 2, 4, 6, 8, and 24 hours after drug administration on days 1, 8, 15, 22, and 29 to evaluate the pharmacokinetics of meloxicam. On day 30, an additional sample was collected 36 hours after treatment. Plasma meloxicam concentrations were quantified with liquid chromatography-mass spectrometry, and noncompartmental pharmacokinetic analysis was performed. Weekly plasma biochemical analyses were performed to evaluate any adverse physiologic effects. Rabbits were euthanatized for necropsy on day 31. Mean ± SD peak plasma concentrations of meloxicam after administration of doses 1, 8, 15, 22, and 29 were 0.67 ± 0.19 μg/mL, 0.81 ± 0.21 μg/mL, 1.00 ± 0.31 μg/mL, 1.00 ± 0.29 μg/mL, and 1.07 ± 0.19 μg/mL, respectively; these concentrations did not differ significantly among doses 8 through 29. Results of plasma biochemical analyses were within reference ranges at all time points evaluated. Gross necropsy and histologic examination of tissues revealed no clinically relevant findings. Plasma concentrations of meloxicam for rabbits in the present study were similar to those previously reported in rabbits that received 1. 0 mg of meloxicam/kg, PO every 24 hours, for 5 days. Results suggested that a dosage of 1. 0 mg/kg, PO, every 24 hours for up to 29 days may be safe for use in healthy rabbits.

  8. Effects of ceftriaxone on glial glutamate transporters in Wistar rats administered sequential ethanol and methamphetamine

    Directory of Open Access Journals (Sweden)

    Yusuf S Althobaiti

    2016-09-01

    Full Text Available Methamphetamine (METH is one of the psychostimulants that is co-abused with ethanol. Repeated high doses of METH have been shown to cause increases in extracellular glutamate concentration. We have recently reported that ethanol exposure can also increase the extracellular glutamate concentration and downregulate glutamate transporter subtype 1 (GLT-1. GLT-1 is a glial transporter that regulates the majority of extracellular glutamate. A Wistar rat model of METH and ethanol co-abuse was used to examine the expression of GLT-1 as well as other glutamate transporters (xCT and GLAST. We also examined the body temperature in rats administered METH, ethanol or both drugs. We further investigated the effects of ceftriaxone (CEF, a β-lactam antibiotic known to upregulate GLT-1, in this METH/ethanol co-abuse rat model. After seven days of either ethanol (6 g/kg or water oral gavage, Wistar rats received either saline or METH (10 mg/kg i.p. every 2 hrs x 4, followed by either saline or CEF (200 mg/kg posttreatment. METH administered alone decreased GLT-1 expression in the NAc and PFC and increased body temperature, but did not reduce either xCT or GLAST expression in ethanol and water-pretreated rats. Interestingly, ethanol and METH were found to have an additive effect on the downregulation of GLT-1 expression in the NAc but not in the PFC. Moreover, ethanol alone caused GLT-1 downregulation in the NAc and elevated body temperature compared to control. Finally, CEF posttreatment significantly reversed METH-induced hyperthermia, restored GLT-1 expression, and increased xCT expression. These findings suggest the potential therapeutic role of CEF against METH- or ethanol/METH-induced hyperglutamatergic state and hyperthermia.

  9. 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 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 meglumine and fenbendazole and known drug metabolizing genes.

  10. Steroids administered after vacuum-assisted biopsy in the management of idiopathic granulomatous mastitis.

    Science.gov (United States)

    Deng, J Q; Yu, L; Yang, Y; Feng, X J; Sun, J; Liu, J; Fan, F S; Liao, L Q

    2017-10-01

    The aetiology and treatment options for idiopathic granulomatous mastitis (IGM) are controversial. The aim was to study the clinical and diagnostic features and discuss medical and surgical treatment for IGM in our patients. Sixty-five patients who met the histological criteria for IGM were retrospectively studied. The diagnosis of IGM was confirmed using Mammotome (an ultrasound-guided, vacuum-assisted biopsy system), core needle biopsy, quadrantectomy or segmental resection. Forty-five patients were treated with prednisolone (69.2%). Immunohistochemical (IHC) staining for immune-related antigens (CD3, CD4, CD8, CD79a, IgG, and IgM) was performed. Ultrasonography (USG) was carried out in all patients. Among them, 61 were considered to have an inflammatory mass and 15 had accompanying liquefaction. In four patients, the findings mimicked breast carcinoma (6.2%). The IHC results showed CD3, CD4, CD8 and CD79a lymphocytes diffusely distributed in the lesion. Stains for IgG and IgM were negative. Prednisolone was administered to the patients diagnosed with IGM. The success rate was 53 (81.5%) and the whole recurrence was 12 (18.5%). The median follow-up period was 12 months (range 4-42 months). The aetiology of IGM remains uncertain. The disease has no propensity for the right or left breast. It is a local autoimmune disease, involving humoral and cell-mediated immunity. Hyperprolactinaemia may play a role in some patients. Corticosteroids administered after complete removal of the IGM lesion using the Mammotome biopsy system is an effective treatment option. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  11. A New Paradigm for Credibly Administering Placebo Alcohol to Underage Drinkers

    Science.gov (United States)

    Bernstein, Michael H.; Colby, Suzanne M.

    2015-01-01

    Background The primary goal of this study was to establish a paradigm for credibly administering placebo alcohol to underage drinkers. We also sought to create a new, valid procedure for establishing placebo alcohol believability. Method Participants were 138 American college students (66.7% female) predominantly (90.0%) under the legal drinking age. Groups of 2–3 participants and one same-sex confederate consumed mixed drinks, purportedly containing alcohol, ad-lib in a naturalistic bar-laboratory for 20 minutes. All beverages, however, were non-alcoholic but we used visual, olfactory, and taste cues to maximize placebo credibility. Also, the confederate made two scripted statements designed to increase the perception of drinking real alcohol. After the drinking portion, participants responded to survey items related to alcohol consumption and intoxication. Next, they were individually debriefed, with open-ended responses used to make a determination of whether the participant was deceived with respect to placebo alcohol. Results All participants estimated consuming some amount of alcohol. However, using a more conservative criteria for estimating alcohol believability based on the debrief, 89.1% of participants were classified as deceived. Deceived participants were much more likely to estimate having a positive Blood Alcohol Content, and to say their current level of intoxication was typical given the amount of alcohol consumed than non-deceived participants. Discussion Credibly administering placebo alcohol to underage drinkers is possible. This approach carries great potential for future laboratory work. In addition, the methodology used here to classify participants as deceived or not deceived appears valid based on self-reported BAC estimation and intoxication levels. PMID:26334562

  12. A new paradigm for credibly administering placebo alcohol to underage drinkers.

    Science.gov (United States)

    Bernstein, Michael H; Wood, Mark D; Colby, Suzanne M

    2016-01-01

    The primary goal of this study was to establish a paradigm for credibly administering placebo alcohol to underage drinkers. We also sought to create a new, valid procedure for establishing placebo alcohol believability. Participants were 138 American college students (66.7% female) predominantly (90.0%) under the legal drinking age. Groups of 2-3 participants and one same-sex confederate consumed mixed drinks, purportedly containing alcohol, ad-lib in a naturalistic bar-laboratory for 20 min. All beverages, however, were non-alcoholic but we used visual, olfactory, and taste cues to maximize placebo credibility. Also, the confederate made two scripted statements designed to increase the perception of drinking real alcohol. After the drinking portion, participants responded to survey items related to alcohol consumption and intoxication. Next, they were individually debriefed, with open-ended responses used to make a determination of whether the participant was deceived with respect to placebo alcohol. All participants estimated consuming some amount of alcohol. However, using a more conservative criteria for estimating alcohol believability based on the debrief, 89.1% of participants were classified as deceived. Deceived participants were much more likely to estimate having a positive blood alcohol content and to say that their current level of intoxication was typical given the amount of alcohol consumed than non-deceived participants. Credibly administering placebo alcohol to underage drinkers is possible. This approach carries great potential for future laboratory work. In addition, the methodology used here to classify participants as deceived or not deceived appears valid based on self-reported BAC estimation and intoxication levels. Copyright © 2015. Published by Elsevier Ltd.

  13. TCDD administered on activated carbon eliminates bioavailability and subsequent shifts to a key murine gut commensal.

    Science.gov (United States)

    Stedtfeld, Robert D; Brett Sallach, J; Crawford, Robert B; Stedtfeld, Tiffany M; Williams, Maggie R; Waseem, Hassan; Johnston, Cliff T; Li, Hui; Teppen, Brian J; Kaminski, Norbert E; Boyd, Stephen A; Tiedje, James M; Hashsham, Syed A

    2017-08-15

    Activated carbon (AC) is an increasingly attractive remediation alternative for the sequestration of dioxins at contaminated sites globally. However, the potential for AC to reduce the bioavailability of dioxins in mammals and the residing gut microbiota has received less attention. This question was partially answered in a recent study examining 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced hallmark toxic responses in mice administered with TCDD sequestered by AC or freely available in corn oil by oral gavage. Results from that study support the use of AC to significantly reduce the bioavailability of TCDD to the host. Herein, we examined the bioavailability of TCDD sequestered to AC on a key murine gut commensal and the influence of AC on the community structure of the gut microbiota. The analysis included qPCR to quantify the expression of segmented filamentous bacteria (SFB) in the mouse ileum, which has responded to TCDD-induced host toxicity in previous studies and community structure via sequencing the 16S ribosomal RNA (rRNA) gene. The expression of SFB 16S rRNA gene and functional genes significantly increased with TCDD administered with corn oil vehicle. Such a response was absent when TCDD was sequestered by AC. In addition, AC appeared to have a minimal influence on murine gut community structure and diversity, affecting only the relative abundance of Lactobacillaceae and two other groups. Results of this study further support the remedial use of AC for eliminating bioavailability of TCDD to host and subsequent influence on the gut microbiome.

  14. 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.

  15. Strain-dependent induction of cytokine profiles in the gut by orally administered Lactobacillus strains.

    Science.gov (United States)

    Maassen, C B; van Holten-Neelen, C; Balk, F; den Bak-Glashouwer, M J; Leer, R J; Laman, J D; Boersma, W J; Claassen, E

    2000-05-22

    Different Lactobacillus strains are frequently used in consumer food products. In addition, recombinant lactobacilli which contain novel expression vectors can now be used in immunotherapeutic applications such as oral vaccination strategies and in T cell tolerance induction approaches for autoimmune disease. Both for food and clinical applications of lactobacilli, proper selection of wild type strains is crucial. For that purpose, eight different common Lactobacillus strains were analysed with respect to mucosal induction of pro- and anti-inflammatory cytokines, IgA-producing plasma cells in the gut, as well as systemic antibody responses against a parenterally administered antigen. Immunohistochemical analysis of cytokine-producing cells in the gut villi showed no significant induction of the cytokines IL-1alpha, IFN-gamma, IL-4 or IL-10 after oral administration of wild type Lactobacillus strains. In contrast, oral administration of L. reuteri and L. brevis induced expression of the proinflammatory/Th1 cytokines TNF-alpha, IL-2 and/or IL-1beta. Oral administration of these two strains and L. fermentum also significantly enhanced the IgG response against parenterally administered haptenated chicken gamma globulin (TNP-CGG). The five other strains did not show this adjuvanticity. L. reuteri induced relatively high levels of IgG2a compared to L. murines, a nonadjuving Lactobacillus strain. These findings imply that different Lactobacillus strains induce distinct mucosal cytokine profiles and possess differential intrinsic adjuvanticity. This suggests that rational Lactobacillus strain selection provides a strategy to influence cytokine expression and thereby influence immune responses.

  16. Muscle protein metabolism in neonatal alloxan-administered rats: effects of continuous and intermittent swimming training.

    Science.gov (United States)

    Ribeiro, Carla; Cambri, Lucieli T; Dalia, Rodrigo A; Araújo, Michel B; Ghezzi, Ana C; Moura, Leandro P; Araújo, Gustavo G; Botezelli, Jose D; Mello, Maria Ar

    2012-02-06

    This study aimed to examine the effects of intermittent and continuous swimming training on muscle protein metabolism in neonatal alloxan-administered rats. Wistar rats were used and divided into six groups: sedentary alloxan (SA), sedentary control (SC), continuous trained alloxan (CA), intermittent trained alloxan (IA), continuous trained control (CC) and intermittent trained control (IC). Alloxan (250 mg/kg body weight) was injected into newborn rats at 6 days of age. The continuous training protocol consisted of 12 weeks of swimming training in individual cylinder tanks while supporting a load that was 5% of body weight; uninterrupted swimming for 1 h/day, five days a week. The intermittent training protocol consisted of 12 weeks of swimming training in individual cylinder tanks while supporting a load that was 15% of body weight; 30 s of activity interrupted by 30 s of rest for a total of 20 min/day, five days a week. At 28 days, the alloxan animals displayed higher glycemia after glucose overload than the control animals. No differences in insulinemia among the groups were detected. At 120 days, no differences in serum albumin and total protein among the groups were observed. Compared to the other groups, DNA concentrations were higher in the alloxan animals that were subjected to continuous training, whereas the DNA/protein ratio was higher in the alloxan animals that were subjected to intermittent training. It was concluded that continuous and intermittent training sessions were effective in altering muscle growth by hyperplasia and hypertrophy, respectively, in alloxan-administered animals.

  17. Muscle protein metabolism in neonatal alloxan-administered rats: effects of continuous and intermittent swimming training

    Directory of Open Access Journals (Sweden)

    Ribeiro Carla

    2012-02-01

    Full Text Available Abstract Background This study aimed to examine the effects of intermittent and continuous swimming training on muscle protein metabolism in neonatal alloxan-administered rats. Methods Wistar rats were used and divided into six groups: sedentary alloxan (SA, sedentary control (SC, continuous trained alloxan (CA, intermittent trained alloxan (IA, continuous trained control (CC and intermittent trained control (IC. Alloxan (250 mg/kg body weight was injected into newborn rats at 6 days of age. The continuous training protocol consisted of 12 weeks of swimming training in individual cylinder tanks while supporting a load that was 5% of body weight; uninterrupted swimming for 1 h/day, five days a week. The intermittent training protocol consisted of 12 weeks of swimming training in individual cylinder tanks while supporting a load that was 15% of body weight; 30 s of activity interrupted by 30 s of rest for a total of 20 min/day, five days a week. Results At 28 days, the alloxan animals displayed higher glycemia after glucose overload than the control animals. No differences in insulinemia among the groups were detected. At 120 days, no differences in serum albumin and total protein among the groups were observed. Compared to the other groups, DNA concentrations were higher in the alloxan animals that were subjected to continuous training, whereas the DNA/protein ratio was higher in the alloxan animals that were subjected to intermittent training. Conclusion It was concluded that continuous and intermittent training sessions were effective in altering muscle growth by hyperplasia and hypertrophy, respectively, in alloxan-administered animals.

  18. Interaction Kinetics of Oximes with Native, Phosphylated and Aged Human Acetylcholinesterase

    Science.gov (United States)

    Radić, Zoran; Kalisiak, Jaroslaw; Fokin, Valery V.; Sharpless, K. Barry; Taylor, Palmer

    2010-01-01

    Oximes are commonly used nucleophilic reactivators of alkyl phosphorylated and alkyl methylphosphonylated acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Covalent inhibition of these enzymes by organophosphate (OP) pesticides results typically in phosphorylated enzymes, while covalent inhibition by nerve agent OPs results in methyl phosphonylated cholinesterases. In this study we determined kinetic constants for interaction of three triazole containing oximes with native human AChE, enzyme diethylphosphorylated by paraoxon, enzyme phosphonylated by VX and cyclosarin as well as enzyme aged upon phosphonylation by soman. Stopped-flow kinetics of oxime interaction was monitored using quenching of intrinsic tryptophan fluorescence of AChE as an indicator of oxime binding. Triazole oximes were efficiently synthesized using copper catalyzed cycloaddition between azide and alkyne building blocks (“Click chemistry”). Equilibrium dissociation constants determined for both native enzymes were in low micromolar range for all three oximes, while dissociation constants for phosphylated (phosphorylated and phosphonylated) enzymes were typically one to two orders of magnitude larger. Dissociation constants for interaction with aged enzymes were similar or smaller than those determined for native enzymes. Similar results were obtained with reference oximes, 2PAM and HI6. Association rate constants for formation of oxime complexes were similar for both native, phosphylated and aged enzymes. In summary our data suggest that modification of active site gorge in AChEs by phosphylation of the active serine compromises oxime binding. Dealkylation of phosphonylated enzyme, however opens space in the gorge allowing oximes to bind tighter. PMID:20412789

  19. 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.

  20. Nicotinamide treatment induces behavioral recovery when administered up to 4 hours following cortical contusion injury in the rat.

    Science.gov (United States)

    Hoane, M R; Pierce, J L; Holland, M A; Anderson, G D

    2008-06-26

    Recent studies have demonstrated nicotinamide (NAM), a soluble B-group vitamin, to be an effective treatment in experimental models of traumatic brain injury (TBI). However, research on this compound has been limited to administration regimens starting shortly after injury. This study was conducted to establish the window of opportunity for NAM administration following controlled cortical impact (CCI) injury to the frontal cortex. Groups of rats were assigned to NAM (50 mg/kg), saline (1 ml/kg), or sham conditions and received contusion injuries or sham procedures. Injections of NAM or saline were administered at 15 min, 4 h, or 8 h post-injury, followed by five boosters at 24 h intervals. Following the last injection, blood was taken for serum NAM analysis. Animals were tested on a variety of tasks to assess somatosensory performance (bilateral tactile adhesive removal and vibrissae-forelimb placement) and cognitive performance (reference and working memory) in the Morris water maze. The results of the serum NAM analysis showed that NAM levels were significantly elevated in treated animals. Behavioral analysis on the tactile removal test showed that all NAM-treated groups facilitated recovery of function compared with saline treatment. On the vibrissae-forelimb placing test all NAM-treated groups also were significantly different from the saline-treated group. However, the acquisition of reference memory was only significantly improved in the 15-min and 4-h groups. In the working memory task both the 15-min and 4-h groups also improved working memory compared with saline treatment. The window of opportunity for NAM treatment is task-dependent and extends to 8 h for the sensorimotor tests but only extends to 4 h post-injury in the cognitive tests. These results suggest that a 50 mg/kg treatment regimen starting at the clinically relevant time point of 4 h may result in attenuated injury severity in the human TBI population.

  1. Phase I study of bosutinib, a src/abl tyrosine kinase inhibitor, administered to patients with advanced solid tumors.

    Science.gov (United States)

    Daud, Adil I; Krishnamurthi, Smitha S; Saleh, Mansoor N; Gitlitz, Barbara J; Borad, Mitesh J; Gold, Philip J; Chiorean, Elena G; Springett, Gregory M; Abbas, Richat; Agarwal, Shefali; Bardy-Bouxin, Nathalie; Hsyu, Poe-Hirr; Leip, Eric; Turnbull, Kathleen; Zacharchuk, Charles; Messersmith, Wells A

    2012-02-15

    Bosutinib, a potent ATP-competitive, quinolinecarbonitrile Src/Abl kinase inhibitor, was tested in this first-in-human phase I trial in patients with advanced solid tumor malignancies. This trial was conducted in 2 parts. In part 1 (dose escalation), increasing oral bosutinib doses were administered using a 3 + 3 design. In part 2 (dose expansion), approximately 30 patients each with refractory colorectal, pancreas, or non-small cell lung cancer were treated at the recommended phase II dose (RP2D). Primary efficacy endpoints for part 2 were median progression-free survival (colorectal and non-small cell lung) and median overall survival (pancreas). In part 1, dose-limiting toxicities of grade 3 diarrhea (two patients) and grade 3 rash occurred with bosutinib 600 mg/day and the maximum tolerated dose identified was 500 mg/day. However, the majority of patients treated with 500 mg/day had grade 2 or greater gastrointestinal toxicity, and 400 mg/day was identified as the RP2D. The most common bosutinib-related adverse events were nausea (60% patients), diarrhea (47%), vomiting (40%), fatigue (38%), and anorexia (36%). Bosutinib had a mean half-life of 19 to 20 hours at the RP2D. A partial response (breast) and unconfirmed complete response (pancreas) were observed; 8 of 112 evaluable patients had stable disease for 22 to 101 weeks. However, the primary efficacy endpoints for part 2 were not met. Bosutinib was generally well tolerated in patients with solid tumors, with the main toxicity being gastrointestinal. The RP2D was 400 mg/day orally. Further study of bosutinib is planned in combination regimens. ©2011 AACR.

  2. A randomized, crossover study to evaluate the pharmacokinetics of amantadine and oseltamivir administered alone and in combination.

    Directory of Open Access Journals (Sweden)

    Dennis Morrison

    2007-12-01

    Full Text Available The threat of potential pandemic influenza requires a reevaluation of licensed therapies for the prophylaxis or treatment of avian H5N1 infection that may adapt to man. Among the therapies considered for use in pandemic influenza is the co-administration of ion channel and neuraminidase inhibitors, both to potentially increase efficacy as well as to decrease the emergence of resistant isolates. To better understand the potential for drug interactions, a cross-over, randomized, open-label trial was conducted with amantadine, 100 mg po bid, and oseltamivir, 75 mg po bid, given alone or in combination for 5 days. Each subject (N = 17 served as their own control and was administered each drug alone or in combination, with appropriate wash-out. Co-administration with oseltamivir had no clinically significant effect on the pharmacokinetics (PK of amantadine [mean ratios (90% CI for AUC(0-12 0.93 (0.89, 0.98 and C(max 0.96 (0.90, 1.02]. Similarly, amantadine co-administration did not affect oseltamivir PK [AUC(0-12 0.92 (0.86, 0.99 and C(max 0.85 (0.73, 0.99] or the PK of the metabolite, oseltamivir carboxylate [AUC(0-12 0.98 (0.95, 1.02 and C(max 0.95 (0.89, 1.01]. In this small trial there was no evidence of an increase in adverse events. Although many more subjects would need to be studied to rule out a synergistic increase in adverse events, the combination in this small human drug-drug interaction trial appears safe and without pharmacokinetic consequences.ClinicalTrials.gov NCT00416962.

  3. Intraperitoneal injection of ethanol results in drastic changes in bone metabolism not observed when ethanol is administered by oral gavage.

    Science.gov (United States)

    Iwaniec, Urszula T; Turner, Russell T

    2013-08-01

    Chronic alcohol abuse is associated with increased risk of osteoporosis while light-to-moderate alcohol intake correlates with reduced osteoporosis risk. Addition of alcohol to a liquid diet is often used to model chronic alcohol abuse. Methods to model intermittent drinking (including binge drinking and light-to-moderate consumption) include (i) intragastric administration of alcohol by oral gavage or (ii) intraperitoneal (ip) administration of alcohol by injection. However, it is unclear whether the latter 2 methods produce comparable results. The purpose of this investigation was to determine the skeletal response to alcohol delivered daily by oral gavage or ip injection. Ethanol (EtOH) or vehicle was administered to 4-month-old female Sprague-Dawley rats once daily at 1.2 g/kg body weight for 7 days. Following necropsy, bone formation and bone architecture were evaluated in tibial diaphysis (cortical bone) and proximal tibial metaphysis (cancellous bone) by histomorphometry. mRNA was measured for bone matrix proteins in distal femur metaphysis. Administration of alcohol by gavage had no significant effect on body weight gain or bone measurements. In contrast, administration of the same dose of alcohol by ip injection resulted in reduced body weight, total suppression of periosteal bone formation in tibial diaphysis, decreased cancellous bone formation in proximal tibial metaphysis, and decreased mRNA levels for bone matrix proteins in distal femur. Our findings raise concerns regarding the use of ip injection of EtOH in rodents as a method for modeling the skeletal effects of intermittent exposure to alcohol in humans. This concern is based on a failure of the ip route to replicate the oral route of alcohol administration. Copyright © 2013 by the Research Society on Alcoholism.

  4. Effect of orally administered probiotic E. coli strain Nissle 1917 on intestinal mucosal immune cells of healthy young pigs.

    Science.gov (United States)

    Duncker, Swantje C; Lorentz, Axel; Schroeder, Bernd; Breves, Gerhard; Bischoff, Stephan C

    2006-06-15

    Several beneficial effects of probiotics have been described in studies using rodent disease models and in human patients; however, the underlying mechanisms remained mostly unclear. Only a few studies focused on the effects of probiotics on the intestinal mucosal immune system. Here, we studied the effect of the probiotic strain E. coli Nissle 1917 (EcN) administered orally to young pigs at two concentrations (10(9) and 10(11)CFU/d for 21 days) on the gut-associated lymphatic tissue. This probiotic strain was shown recently to reduce recurrence of inflammation in ulcerative colitis patients. We quantified the number and distribution of intestinal immune cells (granulocytes, mast cells, CD4+, CD8+, CD25+, IgA+ lymphocytes) and the mucosal mRNA expression of cytokines (IFN-gamma, TNF-alpha, TGF-beta, IL-10) and antimicrobial peptides (PR-39, NK-lysin, prepro-defensin-beta 1, protegrins). The number and distribution of cells were highly different between small intestinal and colon segments in all groups, but were not influenced by EcN, except high dose EcN fed pigs (10(11) CFU/d) showing an increase in mucosal CD8+ cells in the ascending colon. The mRNA analysis revealed no changes associated with EcN feeding. In conclusion, according to our analyses EcN has only minor effects on the distribution of mucosal immune cells in the gut of healthy individuals. The well-established preventive effects of EcN might therefore be relate to other mechanisms than simple modulation of immune cell distribution.

  5. 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.

  6. Musquash Estuary: a proposed monitoring framework for the marine protected area and intertidal area administered by Fisheries and Oceans Canada

    National Research Council Canada - National Science Library

    Kennedy, E

    2011-01-01

    ...) and Administered Intertidal Area (AIA) boundaries. The implementation of monitoring, however, may not be undertaken on the scale of the estuary, and this is to be determined at a later date dependent on factors such as partnerships and availability...

  7. Butyrylcholinesterase as a Therapeutic Drug for Protection Against Percutaneous VX

    Science.gov (United States)

    2010-01-01

    ard therapy of atropine, oxime or diazepam . While all of these nimals displayed mild signs of poisoning following VX, the signs ad resolved in 5h and by...Zheng, C.B. Gilley,M.MacDonald, K. Okolotowicz, J.R. Cashman, S.Vyas, J.M.Beck, C.M.Hadad, J. Zhang, Chemical synthesis of twoseriesofnerve agent

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

    African Journals Online (AJOL)

    USER

    2010-06-28

    Jun 28, 2010 ... guidelines of the American Diabetes Association. Based on anthropometric indices and clinical data, patients were stratified ... The World Health Organization. *Corresponding author. E-mail: rabiu34@yahoo.com. ..... Neuroscience, 110: 627-639. Nath D, Heemels M, Anson L (2006). Obesity and Diabetes.

  9. 40 CFR 147.1050 - State-administered program-Class I, II, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Maryland § 147.1050 State-administered program—Class I, II, III, IV, and V wells. The UIC program for Class I, II, III, IV, and V wells in the State of Maryland, except those wells on Indian lands... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I, II...

  10. 40 CFR 147.850 - State-administered program-Class I, III, IV and V wells.

    Science.gov (United States)

    2010-07-01

    ... PROGRAMS Kansas § 147.850 State-administered program—Class I, III, IV and V wells. The UIC program for Class I, III, IV and V wells in the State of Kansas, except those on Indian lands as described in § 147... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I...

  11. The effect of vitamin A supplementation administered with missing vaccines during national immunization days in Guinea-Bissau

    OpenAIRE

    Benn, Christine Stabell; Martins, Cesario; Rodrigues, Amabelia; Ravn, Henrik; Fisker, Ane B?rent; Christoffersen, Dorthe; Aaby, Peter

    2008-01-01

    Background WHO recommends high-dose Vitamin A supplementation (VAS) at vaccination contacts after 6 months of age. It has not been studied whether the effect of VAS on mortality depends on the type of vaccine. We have hypothesized that VAS administered with measles vaccine (MV) is more beneficial than VAS with diphtheria?tetanus?pertussis (DTP) vaccine. We assessed the effect of VAS administered with different vaccines during national immunization days (NIDs). Methods In 2003, VAS was distrib...

  12. 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.

  13. US Human Rights Conduct and International Legitimacy

    DEFF Research Database (Denmark)

    Keating, Vincent Charles

    Did the Bush administration fundamentally harm the international human rights system through its rejection of human rights norms? This is the central question explored within US Human Rights Conduct and International Legitimacy, which analyses the practices of legitimacy between the Bush administ...... nations have followed in America's footsteps, and that the Bush administration's deviation from international norms has served to reaffirm worldwide commitment to human rights....

  14. 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 sexual behavior questionnaire in primary care clinics. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Effect of Mesalamine and Prednisolone on TNBS Experimental Colitis, following Various Doses of Orally Administered Iron

    Directory of Open Access Journals (Sweden)

    John K. Triantafillidis

    2014-01-01

    Full Text Available Background. Experimental data suggest that oral iron (I. supplementation can worsen colitis in animals. Aim. To investigate the influence of various concentrations of orally administered I. in normal gut mucosa and mucosa of animals with TNBS colitis, as well as the influence of Mesalamine (M. and Prednisolone (P. on the severity of TNBS colitis following orally administered I. Methods and Materials. 156 Wistar rats were allocated into 10 groups. Colitis was induced by TNBS. On the 8th day, all animals were euthanatized. Activity of colitis and extent of tissue damage were assessed histologically. The levels of tissue tumor necrosis factor-α (t-TNF-α and tissue malondialdehyde (t-MDA were estimated in all animal groups. Results. Moderate and high I. supplementation induced inflammation in the healthy colon and increased the activity of the experimentally induced TNBS colitis. Administration of M. on TNBS colitis following moderate iron supplementation (0.3 g/Kg diet resulted in a significant improvement in the overall histological score as well as in two individual histological parameters. M. administration, however, did not significantly reduce the t-TNF-α levels (17.67±4.92 versus 14.58±5.71, P=0.102, although it significantly reduced the t-MDA levels (5.79±1.55 versus 3.67±1.39, P=0.000. Administration of M. on TNBS colitis following high iron supplementation (3.0 g/Kg diet did not improve the overall histological score and the individual histological parameters, neither reduced the levels of t-TNF-α (16.57 ± 5.61 versus 14.65±3.88, P=0.296. However, M. significantly reduced the t-MDA levels (5.99±1.37 versus 4.04±1.41, P=0.000. Administration of P. on TNBS colitis after moderate iron supplementation resulted in a significant improvement in the overall histological score as well as in three individual histological parameters. P. also resulted in a significant reduction in the t-TNF-α levels (17.67±4.92 versus 12.64±3

  16. Rationality of administered gentamicin dose in cerebral coma patients treated in an intensive care unit.

    Science.gov (United States)

    Janušonis, Tomas; Mačiulaitis, Romaldas; Sveikata, Audrius; Milašius, Arvydas; Kregždytė, Rima

    2011-01-01

    Gentamicin is still widely used in the treatment of patients in an intensive care unit (ICU). The efficacy of aminoglycosides correlates with the peak serum concentration (Cmax), and the toxicity with the minimum serum concentration (Cmin). The aim of this study was to determine Cmax and Cmin in serum of cerebral coma ICU patients when a dosage of gentamicin of 5 mg/kg body weight was administered once daily; to evaluate the rationality of mentioned dose; and to identify factors associated with these concentrations. Material and METHODS. A total of 24 ICU patients suffering from cerebral coma were included into this analysis. A dosage of gentamicin of 5 mg/kg body weight was administered once a day. Gentamicin concentrations were tested twice after the first dose infusion (immediately and 5 hours after 1-hour infusion). Cmax, Cmin, volume of distribution (Vd), and elimination half-life (T1/2) were obtained. RESULTS. The mean Cmax was 17.96 (SD, 4.31) µg/mL (range, 10.30-27.87 µg/mL). The desirable Cmax (≥ 20 µg/mL) was reached only in 6 patients (25%). Cmin was calculated using a special pharmacokinetic program "Kinetica." Cmin of 0.5 µg/mL was not exceeded in any patient. A correlative analysis indicated a significant inverse direct correlation between Cmax and Vd and between Cmax and treatment duration in the ICU. An inverse correlation was observed between Cmin and T1/2, evaluation of coma according to the Glasgow coma scale, and creatinine clearance. CONCLUSIONS. A dosage of 5 mg/kg body weight once a day was not sufficient in cerebral coma ICU patients. This dose was not associated with the nephrotoxic effect of gentamicin (additional risk factors were absent). It is recommended to obtain gentamicin concentration at two time points following administration of the first dose (e.g., immediately after 1-hour infusion and 5 hours later), and using a special pharmacokinetic software, to calculate a necessary dose and interval of administration.

  17. 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

  18. 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

  19. Metformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activity

    Science.gov (United States)

    Sikora, Joanna; Mateusiak, Łukasz; Mikiciuk-Olasik, Elżbieta; Huttunen, Kristiina M.

    2017-01-01

    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. PMID:28770024

  20. 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.

  1. Self-administered methoxyflurane for procedural analgesia: experience in a tertiary Australasian centre.

    Science.gov (United States)

    Gaskell, A L; Jephcott, C G; Smithells, J R; Sleigh, J W

    2016-04-01

    Methoxyflurane, an agent formerly used as a volatile anaesthetic but that has strong analgesic properties, will soon become available again in the UK and Europe in the form of a small hand-held inhaler. We describe our experience in the use of inhaled methoxyflurane for procedural analgesia within a large tertiary hospital. In a small pilot crossover study of patients undergoing burns-dressing procedures, self-administered methoxyflurane inhalation was preferred to ketamine-midazolam patient-controlled analgesia by five of eight patients. Patient and proceduralist outcomes and satisfaction were recorded from a subsequent case series of 173 minor surgical and radiological procedures in 123 patients performed using inhaled methoxyflurane. The procedures included change of dressing, minor debridement, colonoscopy and incision-and-drainage of abscess. There was a 97% success rate of methoxyflurane analgesia to facilitate these procedures. Limitations of methoxyflurane include maximal daily and weekly doses, and uncertainty regarding its safety in patients with pre-existing renal disease. © 2016 The Association of Anaesthetists of Great Britain and Ireland.

  2. Immunopotentiative effect of polysaccharide from kefir grain, KGF-C, administered orally in mice.

    Science.gov (United States)

    Murofushi, M; Mizuguchi, J; Aibara, K; Matuhasi, T

    1986-08-01

    Since a water-soluble polysaccharide (KGF-C) from the kefir grains was shown to have the property of retarding tumor growth in vivo when administered orally, the effect of KGF-C was examined on antibody responses to thymus-dependent antigen, sheep red blood cells (SRBC), and thymus-independent antigen, dinitrophenyl-Ficoll and trinitrophenyl-lipopolysaccharide. Antibody response in mice intubated with KGF-C was enhanced to low doses of SRBC, but not to optimal or high doses. The optimal dose of KGF-C required for the enhancement was 100 mg/kg body weight. The time-course studies on KGF-C administration implied that KGF-C exerted its effect on the early events of anti-SRBC response. The enhancement was not due to the alteration of kinetics of anti-SRBC responses. Furthermore, the enhancing effect on antibody responses to thymus-independent antigens, such as dinitrophenyl-Ficoll and trinitrophenyl-lipopolysaccharide, was observed neither in nu/nu nor in nu/+ mice, and the effect on delayed-type hypersensitivity response to a low dose of SRBC in normal mice was also found. These findings suggest that the oral immune enhancement by KGF-C is elucidated probably through T-cell but not through B-cell participation.

  3. Uniform brain tumor distribution and tumor associated macrophage targeting of systemically administered dendrimers.

    Science.gov (United States)

    Zhang, Fan; Mastorakos, Panagiotis; Mishra, Manoj K; Mangraviti, Antonella; Hwang, Lee; Zhou, Jinyuan; Hanes, Justin; Brem, Henry; Olivi, Alessandro; Tyler, Betty; Kannan, Rangaramanujam M

    2015-06-01

    Effective blood-brain tumor barrier penetration and uniform solid tumor distribution can significantly enhance therapeutic delivery to brain tumors. Hydroxyl-functionalized, generation-4 poly(amidoamine) (PAMAM) dendrimers, with their small size, near-neutral surface charge, and the ability to selectively localize in cells associated with neuroinflammation may offer new opportunities to address these challenges. In this study we characterized the intracranial tumor biodistribution of systemically delivered PAMAM dendrimers in an intracranial rodent gliosarcoma model using fluorescence-based quantification methods and high resolution confocal microscopy. We observed selective and homogeneous distribution of dendrimer throughout the solid tumor (∼6 mm) and peritumoral area within fifteen minutes after systemic administration, with subsequent accumulation and retention in tumor associated microglia/macrophages (TAMs). Neuroinflammation and TAMs have important growth promoting and pro-invasive effects in brain tumors. The rapid clearance of systemically administered dendrimers from major organs promises minimal off-target adverse effects of conjugated drugs. Therefore, selective delivery of immunomodulatory molecules to TAM, using hydroxyl PAMAM dendrimers, may hold promise for therapy of glioblastoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. 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.

  5. 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...

  6. Treatment of hepatoma with liposome-encapsulated adriamycin administered into hepatic artery of rats.

    Science.gov (United States)

    Sun, Dong-Sheng; Chen, Jiang-Hao; Ling, Rui; Yao, Qing; Wang, Ling; Ma, Zhong; Li, Yu

    2006-08-07

    To observe the therapeutic effects of liposome-encapsulated adriamycin (LADM) on hepatoma in comparison with adriamycin solution (FADM) and adriamycin plus blank liposome (ADM + BL) administered into the hepatic artery of rats. LADM was prepared by pH gradient-driven method. Normal saline, FADM (2 mg/kg), ADM+BL (2 mg/kg), and LADM (2 mg/kg) were injected via the hepatic artery in rats bearing liver W256 carcinosarcoma, which were divided into four groups randomly. The therapeutic effects were evaluated in terms of survival time, tumor enlargement ratio, and tumor necrosis degree. The difference was determined with ANOVA and Dunnett test and log rank test. Compared to FADM or ADM + BL, LADM produced a more significant tumor inhibition (tumor volume ratio: 1.243 +/- 0.523 vs 1.883 +/- 0.708, 1.847 +/- 0.661, P LADM compared with FADM or ADM+BL (231.48 vs 74.66, 94.70) (P < 0.05). The anticancer efficacies of adriamycin on hepatoma can be strongly improved by liposomal encapsulation through hepatic arterial administration.

  7. An interdisciplinary approach to the development of accessible computer-administered measurement instruments.

    Science.gov (United States)

    Magasi, Susan; Harniss, Mark; Heinemann, Allen W

    2017-09-04

    Principles of fairness in testing require that all test takers, including people with disabilities, have an equal opportunity to demonstrate their capacity in the construct being measured. Measurement design features and assessment protocols can pose barriers for people with disabilities. Fairness in testing is a fundamental validity issue at all phases in the design, administration and interpretation of measurement instruments in clinical practice and research. There is limited guidance for instrument developers in how to develop and evaluate the accessibility and usability of measurement instruments. This paper describes a 6-stage iterative process for developing accessible computer-administered measurement instruments based on our work in several major measurement initiatives. Interdisciplinary teams of accessibility experts, content and measurement experts, information technology experts and people with disabilities should work together to ensure that measurement instruments are accessible and usable by a wide range of users. The development of accessible measurement instruments is not only an ethical requirement, it also ensures better science by minimizing measurement bias, missing data, and attrition due to mismatches between the target population and test administration platform and protocols. Copyright © 2017. Published by Elsevier Inc.

  8. Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils

    Science.gov (United States)

    Holguin, Sarah; Martinez, Joseph; Chow, Camille; Wurtman, Richard

    2008-01-01

    This study examined the effects on cognitive behaviors of giving normal adult gerbils three compounds, normally in the circulation, which interact to increase brain phosphatides, synaptic proteins, dendritic spines, and neurotransmitter release. Animals received supplemental uridine (as its monophosphate, UMP; 0.5%) and choline (0.1%) via the diet, and docosahexaenoic acid (DHA; 300 mg/kg/day) by gavage, for 4 wk, and then throughout the subsequent period of behavioral training and testing. As shown previously, giving all three compounds caused highly significant (P<0.001) increases in total brain phospholipids and in each major phosphatide; giving DHA or UMP (plus choline) produced smaller increases in some of the phosphatides. DHA plus choline improved performance on the four-arm radial maze, T-maze, and Y-maze tests; coadministering UMP further enhanced these increases. (Uridine probably acts by generating both CTP, which can be limiting in phosphatide synthesis, and UTP, which activates P2Y receptors coupled to neurite outgrowth and protein synthesis. All three compounds also act by enhancing the substrate-saturation of phosphatide-synthesizing enzymes.) These findings demonstrate that a treatment that increases synaptic membrane content can enhance cognitive functions in normal animals.—Holguin, S., Martinez, J., Chow, C., Wurtman, R. Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils. PMID:18606862

  9. Intraperitoneally administered biliverdin protects against UVB-induced skin photo-damage in hairless mice.

    Science.gov (United States)

    Bai, Bingxue; Liu, Yingdi; You, Yan; Li, Yuzhen; Ma, Liangjuan

    2015-03-01

    Oxidative stress is shown to be responsible for ultraviolet B (UVB) irradiation-induced skin cancer and premature aging. Biliverdin (BVD), a product of heme oxygenase-1, has strong anti-oxidant and anti-inflammatory properties. In the present study, we investigated the effects of BVD on UVB-induced skin photo-damage in hairless mice. Mice were divided into three groups: control group, UVB group (only UVB irradiation) and BVD+UVB group (mice were intraperitoneally injected with BVD before each UVB irradiation). Intraperitoneal BVD injection resulted in a significant photoprotective effect by reducing morphological and histopathological changes to the skin. BVD also exhibited a significant antioxidant effect by increasing the superoxide dismutase (SOD) level and decreasing the thiobarbituric acid reactive substances (TBARS) level compared with the control group. In addition, BVD activated biliverdin reductase (BVR) expression and inhibited the UVB-induced increase of p38 mitogen-activated protein kinase phosphorylation (p-p38MAPK), MMP (matrix metalloproteinase)-1 and MMP-3 expression (p<0.05). It also significantly decreased the interleukin (IL)-6 level compared with the UVB group (p<0.05). In conclusion, these data suggest that the intraperitoneally administered BVD can prevent UVB irradiation-induced skin photo-damage in hairless mice and that this is likely mediated by its antioxidant and anti-inflammatory mechanisms and cell signal regulatory action. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. A Self-Administered Stress Management Intervention for Hispanic Patients Undergoing Cancer Chemotherapy.

    Science.gov (United States)

    Loi, Claudia X Aguado; Nesman, Teresa M; Xu, Ping; Taylor, Teletia R; McMillan, Susan; Krischer, Jeffrey P; Tyc, Vida L; Gross-King, Margaret; Huegel, Viki

    2016-11-05

    This study evaluated whether a self-administered stress management training (SSMT) could improve quality of life (QOL) and reduce distress among Hispanics receiving chemotherapy across multiple community clinical settings. Participants were randomized to receive SSMT (n = 106) or usual care (UCO) (n = 113). The primary outcome-QOL (SF-36) and secondary outcomes depression (CES-D), and anxiety (STAI) were assessed longitudinally over four chemotherapy cycles. Acculturation (BAS) and patients' intervention adherence were assessed. About 63% of participants reported distress after the initial chemotherapy cycle. Hispanics with lower acculturation reported greater STAI-Trait scores (p = .003). No significant treatment effects on outcomes measures were observed for participants receiving SSMT. SSMT intervention techniques were reported useful and improved mental health scores were observed with patients on a psychotropic agent (p = .04). Hispanics experience an elevated level of distress, yet SSMT did not significantly improve primary outcomes. SSMT may be potentially effective when combined with a psychotropic agent. SSMT enhancing strategies are discussed.

  11. Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines.

    Science.gov (United States)

    Hayashi, Masayuki; Aoshi, Taiki; Haseda, Yasunari; Kobiyama, Kouji; Wijaya, Edward; Nakatsu, Noriyuki; Igarashi, Yoshinobu; Standley, Daron M; Yamada, Hiroshi; Honda-Okubo, Yoshikazu; Hara, Hiromitsu; Saito, Takashi; Takai, Toshiyuki; Coban, Cevayir; Petrovsky, Nikolai; Ishii, Ken J

    2017-02-01

    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 (Th)2-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. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Effect of Orally Administered Collagen Peptides from Bovine Bone on Skin Aging in Chronologically Aged Mice

    Directory of Open Access Journals (Sweden)

    Hongdong Song

    2017-11-01

    Full Text Available Collagen peptides (CPs have demonstrated to exert beneficial effects on skin photoaging. However, little has been done to evaluate their effects on chronologically aged skin. Here, the effects of CPs from bovine bone on skin aging were investigated in chronologically aged mice. 13-month-old female Kunming mice were administered with CPs from bovine bone (200, 400 and 800 mg/kg body weight/day or proline (400 mg/kg body weight/day for 8 weeks. Mice body weight, spleen index (SI and thymus index (TI, degree of skin laxity (DSL, skin components, skin histology and antioxidant indicators were analyzed. Ingestion of CPs or proline had no effect on mice skin moisture and hyaluronic acid content, but it significantly improved the skin laxity, repaired collagen fibers, increased collagen content and normalized the ratio of type I to type III collagen in chronologically aged skin. CPs prepared by Alcalase performed better than CPs prepared by collagenase. Furthermore, CPs intake also significantly improved the antioxidative enzyme activities in skin. These results indicate that oral administration of CPs from bovine bone or proline can improve the laxity of chronologically aged skin by changing skin collagen quantitatively and qualitatively, and highlight their potential application as functional foods to combat skin aging in chronologically aged process.

  13. Effect of Intravenously Administered Crystalloid Solutions on Acid-Base Balance in Domestic Animals.

    Science.gov (United States)

    Muir, W

    2017-09-01

    Intravenous fluid therapy can alter plasma acid-base balance. The Stewart approach to acid-base balance is uniquely suited to identify and quantify the effects of the cationic and anionic constituents of crystalloid solutions on plasma pH. The plasma strong ion difference (SID) and weak acid concentrations are similar to those of the administered fluid, more so at higher administration rates and with larger volumes. A crystalloid's in vivo effects on plasma pH are described by 3 general rules: SID > [HCO3-] increases plasma pH (alkalosis); SID acidity. Appreciation of IV fluid composition and an understanding of basic physicochemical principles provide therapeutically valuable insights about how and why fluid therapy can produce and correct alterations of plasma acid-base equilibrium. The ideal balanced crystalloid should (1) contain species-specific concentrations of key electrolytes (Na(+) , Cl(-) , K(+) , Ca(++) , Mg(++) ), particularly Na(+) and Cl(-) ; (2) maintain or normalize acid-base balance (provide an appropriate SID); and (3) be isosmotic and isotonic (not induce inappropriate fluid shifts) with normal plasma. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. Comparative hemodynamic effects of three different parenterally administered lipid emulsions in conscious dogs.

    Science.gov (United States)

    Van de Velde, M; Wouters, P F; Rolf, N; Van Aken, H; Vandermeersch, E

    1998-01-01

    To compare the hemodynamic side effects of three structurally different lipid emulsions. Randomized, controlled, prospective animal study. University research laboratory. Six chronically instrumented mongrel dogs. On separate days, all animals were submitted to three different treatments, in a randomized order. After baseline measurements, either a long-chain triglyceride emulsion (treatment 1), a mixed medium-chain triglyceride/long-chain triglyceride emulsion (treatment 2), or an omega3 polyunsaturated fatty acid long-chain triglyceride (PUFA) emulsion (treatment 3) was administered intravenously over 30 mins. Global and regional hemodynamics (sonomicrometry) were recorded for 2 hrs after baseline measurements. Arterial blood gases and plasma concentrations of hemoglobin, triglycerides, total protein, and glucose were recorded for 2 hrs. Long-chain triglycerides did not affect the cardiovascular performance in awake animals. However, medium-chain triglycerides/long-chain triglycerides and omega3 PUFA caused marked increases in systemic vascular resistance (from 1833 +/- 154 to 3277 +/- 163 mm Hg/dynexsec5, p emulsions can cause profound cardiovascular side effects at high doses, depending on their composition. Whereas long-chain triglyceride emulsions have virtually no effects on hemodynamics in normal dogs, medium-chain triglyceride/long-chain triglyceride, and omega3 PUFA emulsions should be used with caution in critically ill patients with compromised cardiovascular function.

  19. Interpretive accuracy of the disk diffusion method for testing newer orally administered cephalosporins against Morganella morganii.

    Science.gov (United States)

    Biedenbach, D J; Jones, R N; Erwin, M E

    1993-01-01

    Eight newer orally administered cephems (cefdinir, cefetamet, cefixime, cefpodoxime, cefprozil, ceftibuten, cefuroxime, and loracarbef) were tested against 100 clinical strains of Morganella morganii to determine the extent of serious interpretive very major (false-susceptible) errors when current criteria for the disk diffusion test are applied. Agar dilution MICs and disk diffusion tests were performed as recommended by the National Committee for Clinical Laboratory Standards (Villanova, Pa.) (NCCLS), and the methods were compared by regression analysis using the method of least squares and by error rate bounding. The following results are listed in the order of increasing error rates: cefdinir, loracarbef, and cefprozil, ceftibuten, 8% minor errors; cefuroxime, 21% minor errors; cefixime, cefpodoxime, and cefetamet, very major errors of 15, 24, and 36%, respectively. M. morganii produces unacceptable rates of test error with cefuroxime, cefixime, cefpodoxime, and cefetamet. The latter two cephalosporins currently have NCCLS table footnote warnings covering the problem observed with this organism. The inclusion of cefuroxime and cefixime in the NCCLS table footnote is strongly recommended. PMID:8253998

  20. Aminothiol Receptors for Decorporation of Intravenously Administered 60Co in the Rat

    Energy Technology Data Exchange (ETDEWEB)

    Levitskaia, Tatiana G.; Morris, James E.; Creim, Jeffrey A.; Woodstock, Angela D.; Luders, Teresa; Curry, Terry L.; Thrall, Karla D.

    2010-01-01

    The reported investigation provides a comparison of the oral decorporation efficacy of L-glutathione (GSH), L-cysteine (Cys), and a liposomal GSH formulation (ReadiSorb) toward systemic cobalt-60 (60Co) to that observed following intravenous administration of GSH and Cys in F344 rats. L-histidine (His) was tested intravenously to compare in vivo efficacy of the aminothiol GSH and Cys chelators with that of aminoimidazole (His) chelator. 60Co was administered to animals by intravenous injection, followed by intravenous or oral gavage doses of a chelator repeated at 24 hour intervals for a total of 5 doses. The results suggest that GSH and Cys are potent decorporation agents for 60Co in the rat model, although the efficacy of treatment depends largely on systemic availability of a chelator. The intravenous GSH or Cys were most effective in reducing tissue 60Co levels and in increasing excretion of radioactivity compared to control animals. Liposomal encapsulation was found to markedly enhance the oral bioavailability of GSH compared to non-formulated GSH. Oral administration of ReadiSorb reduced 60Co levels in nearly all tissues by 12-43% compared to that observed for non-formulated GSH. Efficacy of oral Cys was only slightly reduced in comparison with intravenous Cys. Further studies to optimize the dosing regimen in order to maximize decorporation efficiency are warranted.

  1. Effects of administered alcohol on intimate partner interactions in a conflict resolution paradigm.

    Science.gov (United States)

    Testa, Maria; Crane, Cory A; Quigley, Brian M; Levitt, Ash; Leonard, Kenneth E

    2014-03-01

    Although couples' alcohol use has been associated with intimate partner aggression and poorer marital functioning, few studies have examined the proximal effects of alcohol on couple interactions. The current experimental study examined the effects of alcohol, administered independently to male and female intimate partners, on positive and negative interaction behaviors within a naturalistic conflict resolution paradigm. Married and cohabiting couples (n = 152) were recruited from the community and each partner randomly assigned to receive either alcohol (target dose: .08 mg/kg) or no alcohol. They engaged in two 15-minute interactions regarding current disagreements in their relationship, one before and one after beverage administration. Videotaped interactions were coded by trained observers using the Rapid Marital Interaction Coding System, and positive and negative interaction behaviors were analyzed using the Actor-Partner Interdependence Model. Participants displayed decreased negativity and increased positivity following alcohol consumption when their partners were sober but no differences in negativity or positivity when their partners also consumed alcohol. There were no gender differences. Although participants with a history of perpetrating intimate partner aggression displayed more negativity, prior aggression did not interact with beverage condition. The immediate effects of alcohol consumption on couple interaction behaviors appeared more positive than negative. Contrary to hypotheses, congruent partner drinking had neither particularly positive nor particularly negative effects. These unique findings represent a rare glimpse into the immediate consequences of alcohol consumption on couple interaction and stand in contrast to its delayed or long-term effects.

  2. Ethnopharmacological Evaluation of Breu Essential Oils from Protium Species Administered by Inhalation

    Directory of Open Access Journals (Sweden)

    Eduardo Rodrigues da Silva

    2017-01-01

    Full Text Available Background. Breu is an aromatic oleoresin which has been used by Amazonian traditional communities as a remedy for headaches and migraines by burning and inhaling the smoke produced during its combustion. This study evaluated the antinociceptive and sedative activities of formulations containing breu essential oils administered by inhalation. Methods. Five different formulations (A–E containing breu essential oils were evaluated for their sedative and antinociceptive activities in mice. They were delivered for 20 minutes using an inhalation chamber coupled with a nebulizer and the air inside was collected by static headspace and analyzed by GC-FID. Results. All nebulized formulations had similar chemical compositions and major compounds as the original essential oils. None of them resulted in significant increase in response time during the hot plate test. In the formalin test, Formulation E showed a significant inhibition of licking responses in the early (46.8% and late (60.2% phases. Formulation B was effective (36.9% in the first phase and Formulation D (37.9% in the second. None of the formulations presented sedative effects. Conclusion. Breu essential oils, when inhaled, may present antinociceptive and anti-inflammatory properties without sedation. Additionally, nebulization proved to be an efficient method for administration of formulations containing these essential oils.

  3. [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.

  4. 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.

  5. Administering the "AHSP Questionnaire" (appetite, hunger, sensory perception) in a geriatric rehabilitation care.

    Science.gov (United States)

    Savina, C; Donini, L M; Anzivino, R; De Felice, M R; De Bernardini, L; Cannella, C

    2003-01-01

    Frail elderly people, living in nursing homes, usually show a malnutrition state caused by an increased need of energy or an inadequate food intake. Among the causes leading to reduction of food intake in elderly people and consequently to malnutrition, is the loss of appetite, often marker of depression and alterations of taste and smell perception. The aim of this research is to verify the application of the AHSP Questionnaire and relate its score to nutritional state of a frail elderly population hospitalized in a geriatric rehabilitation care. All patients of the "3rd Rehabilitation Department" of the Istituto Geriatrico "Villa delle Querce" Nemi (Rome-Italy). Informations, number and type of medical conditions, prescribed drugs, other parameters that can affect taste, smell, hunger and nutritional status, mood, cognitive and nutritional status have been collected from the clinical folders. To assess appetite, hunger smell and taste perception had been submitted the AHSP Questionnaire. The AHSP Questionnaire had been administered only to 44 of the 103 patients present at the survey because of the high prevalence of cognitive impairment. AHSP score is lower in presence of malnutrition assessed with MNA (Mini Nutritional Assessment). MNA, expressed as proportional score, seems to present a clear correlation with AHSP's (r=0.59; p=0.000). The results achieved show the scarce adaptability of the AHSP Questionnaire to frail elderly people living in geriatric rehabilitation care. MNA is at the moment the most reliable tool to single out dietary deficiency on geriatrics population.

  6. The influence of administering "effective microorganisms" to pullets on chosen haematological and biochemical blood indexes.

    Science.gov (United States)

    Sokół, R; Michalczyk, M; Spodniewska, A; Barski, D

    2009-01-01

    "Effective Microorganisms" (EM)--a mixture of lactic acid bacteria, photosynthetic bacteria, yeasts and fungi are used mainly in agriculture and organic waste treatment. Recently, they have also been added to water and feed for animals, as well as to processing their excrements into compost and to eliminate the stench. The objective of the present study was to assess the influence of a 14-day administration of an EM solution in drinking water to layer hens on chosen haematological and biochemical indexes. The research was carried out on 120 hens divided into two equal groups. The birds in the experimental group were given drinking water with dissolved EM (5% solution), and those in the control group--water without the preparation. On the 64th day of the aviculture, the hens were weighted and their blood was taken from the wing vein for haematological and biochemical examinations. Administering EM with water to hens did not influence significantly their body weight nor chosen haematological and biochemical indexes. A significant increase was found only in the number of platelets, the level of albumins, the content of total cholesterol and the LDH activity, however, a decrease in the ALT activity was observed.

  7. Estimations of water balance after validating and administering the water balance questionnaire in pregnant women.

    Science.gov (United States)

    Malisova, Olga; Protopappas, Athanasios; Nyktari, Anastasia; Bountziouka, Vassiliki; Antsaklis, Aristides; Zampelas, Antonis; Kapsokefalou, Maria

    2014-05-01

    Dehydration during pregnancy may be harmful for the mother and fetus; thus our objective was to understand whether pregnant women balance water intake and loss. The Water Balance Questionnaire (WBQ) was modified to reflect pregnancy (WBQ-P). Validation was performed using 3-day diaries (n = 60) and hydration indices in urine (osmolality, specific gravity, pH and color, n = 40). The WBQ-P was found valid according to Kedhal τ-b coefficient agreement. The WBQ-P was administered to 95, 100 and 97 women per trimester, in Greece. Median (IQR) water balance, intake and loss were, respectively, 203 (-577, 971), 2917 (2187, 3544) and 2658 (2078, 3391) ml/day; these did not differ among the trimesters or between pregnant and non-pregnant women. However, more pregnant women were falling in the higher quartiles of water balance distribution. No differences in sources of water intake were identified except that women in the third trimester had lower water intake from beverages.

  8. 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.

  9. Administering ketoconazole (25mg/Kg) For 14 Days in male wistar ...

    African Journals Online (AJOL)

    structures ( amygdala, median emmence, paraventricular and raphe nuclei) and plasma. ACTH increase significantly. These results were also obtained in humans where it was found that chronic administration of KTCN generated a very significant elevation of plasma. ACTH [34]. The inhibition of plasma corticosterone by ...

  10. Digested BLG can induce tolerance when co-administered with intact BLG in Brown Norway rats

    DEFF Research Database (Denmark)

    Bøgh, Katrine Lindholm; Barkholt, Vibeke; Madsen, Charlotte Bernhard

    the human gastro-duodenal digestion process. Four different fractions of BLG-digest was made, based on sizes of peptides or aggregates hereof. Intact BLG and the four fractions of BLG-digesta were characterized by protein chemical analyses. Brown Norway (BN) rats were immunised i.p. three times without...

  11. 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

  12. 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

  13. Self-Administered Mind-Body Practices for Reducing Health Disparities: An Interprofessional Opinion and Call to Action

    Directory of Open Access Journals (Sweden)

    Patricia A. Kinser

    2016-01-01

    Full Text Available Health disparities (HD continue to persist in the United States which underscores the importance of using low-cost, accessible, evidence-based strategies that can improve health outcomes, especially for chronic conditions that are prevalent among underserved minority populations. Complementary/integrative health modalities, particularly self-administered mind-body practices (MBP, can be extremely useful in reducing HD because they are intrinsically patient-centered and they empower patients to actively engage in self-care of health and self-management of symptoms. Interprofessional healthcare providers and patients can engage in powerful partnerships that encompass self-administered MBP to improve health. This is a call to action for interprofessional researchers to engage in high-quality research regarding efficacy and cost-effectiveness of self-administered MBP, for practitioners to engage patients in self-administered MBP for health promotion, disease prevention, and symptom management, and for healthcare institutions to integrate self-administered MBP into conventional health practices to reduce HD in their communities.

  14. 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.

  15. Diagnosing depression in the medically ill: validity of a lay-administered structured diagnostic interview.

    Science.gov (United States)

    Booth, B M; Kirchner, J E; Hamilton, G; Harrell, R; Smith, G R

    1998-01-01

    Understanding the validity of structured psychiatric diagnostic interviews in medically ill patients will advance the ability to conduct research into the treatment and management of these disorders in general medical settings. We compared the University of Michigan version of the CIDI (Composite International Diagnostic Interview) for major depression to a clinical gold standard, derived through Spitzer's Longitudinal, Expert, All Data (LEAD) criteria based on the SCID-III-R. A convenience sample of medical inpatients was administered the SCID-III-R and the CIDI for major depression in random order. A physician panel reviewed the SCID interview and other pertinent data and determined whether patients had a lifetime or current (past month) diagnosis of major depression. The CIDI was scored with and without hierarchical exclusions for mania, hypomania, substance use, or medical illness. When the UM-CIDI was scored for a lifetime diagnosis of major depression without hierarchical exclusions, agreement above chance (kappa) was very good (kappa = 0.67) between the CIDI and the physician panel and good (kappa = 0.46) when the UM-CIDI was scored with exclusions. Agreement above chance for diagnosis of a recent disorder was better for UM-CIDI scoring with exclusions (kappa = 0.51) compared to scoring without exclusions (kappa = 0.43). Predictive value-positive was excellent in both scoring versions for a lifetime diagnosis (82%) and good to very good for current depression (46% and 62%). In all cases predictive value-negative was very good to excellent (77-93%). Discordant cases were almost uniformly due to difficulties in attribution of symptoms to medical illnesses. We conclude that the CIDI can perform acceptably as a research instrument to diagnose major depression in medically ill patients, potentially supplemented by clinician review of cases identified by the CIDI with current disorder.

  16. 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.

  17. Valproate administered after traumatic brain injury provides neuroprotection and improves cognitive function in rats.

    Directory of Open Access Journals (Sweden)

    Pramod K Dash

    Full Text Available BACKGROUND: Traumatic brain injury (TBI initiates a complex series of neurochemical and signaling changes that lead to pathological events including neuronal hyperactivity, excessive glutamate release, inflammation, increased blood-brain barrier (BBB permeability and cerebral edema, altered gene expression, and neuronal dysfunction. It is believed that a drug combination, or a single drug acting on multiple targets, may be an effective strategy to treat TBI. Valproate, a widely used antiepileptic drug, has a number of targets including GABA transaminase, voltage-gated sodium channels, glycogen synthase kinase (GSK-3, and histone deacetylases (HDACs, and therefore may attenuate a number of TBI-associated pathologies. METHODOLOGY/PRINCIPAL FINDINGS: Using a rodent model of TBI, we tested if post-injury administration of valproate can decrease BBB permeability, reduce neural damage and improve cognitive outcome. Dose-response studies revealed that systemic administration of 400 mg/kg (i.p., but not 15, 30, 60 or 100 mg/kg, increases histone H3 and H4 acetylation, and reduces GSK-3 activity, in the hippocampus. Thirty min post-injury administration of 400 mg/kg valproate improved BBB integrity as indicated by a reduction in Evans Blue dye extravasation. Consistent with its dose response to inhibit GSK-3 and HDACs, valproate at 400 mg/kg, but not 100 mg/kg, reduced TBI-associated hippocampal dendritic damage, lessened cortical contusion volume, and improved motor function and spatial memory. These behavioral improvements were not observed when SAHA (suberoylanilide hydroxamic acid, a selective HDAC inhibitor, was administered. CONCLUSION/SIGNIFICANCE: Our findings indicate that valproate given soon after TBI can be neuroprotective. As clinically proven interventions that can be used to minimize the damage following TBI are not currently available, the findings from this report support the further testing of valproate as an acute therapeutic strategy.

  18. The effect of desmopressin on bleeding time and platelet aggregation in healthy volunteers administered ticagrelor.

    Science.gov (United States)

    Teng, R; Mitchell, P D; Butler, K

    2014-04-01

    Ticagrelor is a reversibly binding and selective P2Y12 -receptor antagonist approved for the prevention of atherothrombotic events in patients with acute coronary syndromes. As bleeding events remain a hazard with antiplatelet therapy, this study investigated the effect of the vasopressin agonist, desmopressin, on ticagrelor-induced bleeding time prolongation. Desmopressin has previously been shown to improve primary haemostasis and is widely used as first-line therapy for individuals with bleeding disorders. In a randomized, double-blind, 2-period crossover study, healthy volunteers received ticagrelor (270 mg loading dose; 180 mg bid) for 5 days. On Day 5, desmopressin (0·3 μg/kg) or saline intravenous infusions were administered. The impact of desmopressin on bleeding time, inhibition of platelet aggregation (IPA), platelet function and ticagrelor pharmacokinetic parameters was investigated. Twenty-one volunteers (81% male) were enrolled. Median [range] bleeding times were slightly reduced with ticagrelor plus desmopressin compared with ticagrelor alone (7·50 [3-17] vs. 10·50 [3-25] min at 2·5 h). Median reductions in bleeding time from baseline were generally similar between ticagrelor plus desmopressin compared with ticagrelor alone at all time points. Co-administration of desmopressin had no impact on IPA, although platelet reactivity was significantly increased (von Willebrand Factor antigen: GLS mean AUEC was 4667%.h for ticagrelor plus desmopressin compared with 2750%.h for ticagrelor alone). Desmopressin did not influence the pharmacokinetics of ticagrelor. Desmopressin had no significant effect on bleeding time or inhibition of platelet aggregation by ticagrelor, although primary haemostatic activity was significantly increased. Ticagrelor pharmacokinetic parameters were not affected by co-administration with desmopressin. Therefore, desmopressin is unlikely to be an effective therapeutic agent for control of the potential bleeding events

  19. Impact of in ovo-administered lead and testosterone on developing female thymocytes.

    Science.gov (United States)

    Hussain, Irshad; Piepenbrink, Michael S; Dietert, Rodney R

    2005-08-13

    The developing immune system is particularly sensitive to lead-induced immunotoxicity, but in some models, genders can differ in lead-induced immunotoxicity. Using an avian in ovo model of lead-induced T-helper disruption, the ability of in ovo administered lead and testosterone to alter thymocyte maturation among female embryos was investigated. On embryonic day (E) 8, Cornell K-strain embryos were given either testosterone (12.5 microg/egg in ethanol) or 15% ethanol in 100 microl volume. The groups then received either lead acetate (200 microg/egg) or sodium acetate (control) on E 12 of incubation. On E 20, thymocytes from 4-5 female embryos per group were analyzed by flow cytometry for cell surface markers CD3, CD4, CD8, TCR1, and TCR2. Lead alone did not induce any appreciable changes among the cell populations measured in this study. However, when testosterone treatment was followed by lead (testosterone + lead), there was a significant increase in CD4+CD8+ double-positive cells compared with either control or lead treatment groups. Testosterone, either by itself or in combination with lead, significantly reduced the percentage of cells with the CD4+CD8- phenotype when compared to the lead alone group. No change was detected with respect to the CD4-CD8+, CD4-CD8-, TCR1+, and TCR2+ phenotypes following any treatment. Therefore, sex hormonal balance in early life appears to influence the manner in which the developing thymus responds to the heavy metal lead.

  20. 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.

  1. Reduction of Pavlovian Bias in Schizophrenia: Enhanced Effects in Clozapine-Administered Patients.

    Directory of Open Access Journals (Sweden)

    Matthew A Albrecht

    Full Text Available The negative symptoms of schizophrenia (SZ are associated with a pattern of reinforcement learning (RL deficits likely related to degraded representations of reward values. However, the RL tasks used to date have required active responses to both reward and punishing stimuli. Pavlovian biases have been shown to affect performance on these tasks through invigoration of action to reward and inhibition of action to punishment, and may be partially responsible for the effects found in patients. Forty-five patients with schizophrenia and 30 demographically-matched controls completed a four-stimulus reinforcement learning task that crossed action ("Go" or "NoGo" and the valence of the optimal outcome (reward or punishment-avoidance, such that all combinations of action and outcome valence were tested. Behaviour was modelled using a six-parameter RL model and EEG was simultaneously recorded. Patients demonstrated a reduction in Pavlovian performance bias that was evident in a reduced Go bias across the full group. In a subset of patients administered clozapine, the reduction in Pavlovian bias was enhanced. The reduction in Pavlovian bias in SZ patients was accompanied by feedback processing differences at the time of the P3a component. The reduced Pavlovian bias in patients is suggested to be due to reduced fidelity in the communication between striatal regions and frontal cortex. It may also partially account for previous findings of poorer "Go-learning" in schizophrenia where "Go" responses or Pavlovian consistent responses are required for optimal performance. An attenuated P3a component dynamic in patients is consistent with a view that deficits in operant learning are due to impairments in adaptively using feedback to update representations of stimulus value.

  2. Effects of Self-Administered Methamphetamine on Discrimination Learning and Reversal in Nonhuman Primates

    Science.gov (United States)

    Kangas, Brian D.; Bergman, Jack

    2015-01-01

    Rationale Frequent exposure to methamphetamine has been reported to adversely influence cognitive behavior and, in particular, inhibitory control processes. Objective The present studies were conducted in squirrel monkeys to assess the effects of daily intravenous methamphetamine self-administration on touchscreen-based repeated acquisition and discrimination reversal tasks thought to reflect behavioral dimensions of, respectively, learning and response inhibition. Methods First, stable methamphetamine-maintained behavior was established (0.35-1.6 mg/kg/session) and, subsequently, a second daily session of discrimination learning was conducted (20 hr later). Subjects first learned to discriminate between two simultaneously presented stimuli (acquisition) and, subsequently, to re-learn the discrimination with the contingencies switched (reversal). The role of the interval between self-administration and touchscreen sessions was evaluated, as well as the effects of abrupt methamphetamine discontinuation. Results Results indicate that daily methamphetamine self-administration markedly disrupted the development of discrimination learning, initially requiring nearly twice the number of trials to master discriminations. The magnitude of adverse effects in individual subjects correlated to the level of daily methamphetamine intake. Importantly, however, behavioral disruption of discrimination learning was surmounted following remedial training. Once criterion levels of discrimination performance were achieved, subsequent development of reversal performance was largely unaffected except when the interval between self-administration and touchscreen session was short and, thus, likely vulnerable to methamphetamine’s direct effects. Discontinuation of methamphetamine produced no disruption in acquisition or reversal. Conclusion These results indicate that self-administered methamphetamine can markedly disrupt learning processes and, as well, highlights key differences in

  3. Disposition, behavioural and physiological effects of escalating doses of intravenously administered fentanyl to young foals.

    Science.gov (United States)

    Knych, H K; Steffey, E P; Casbeer, H C; Mitchell, M M

    2015-09-01

    Foal responses to a broader range of plasma fentanyl concentrations than currently reported are desirable to support (or not) clinical use. To describe fentanyl plasma concentrations following an escalating i.v. fentanyl dosing schedule in foals aged 5-13 days and describe selected, associated dose- and time-related behavioural and physiological responses to plasma fentanyl concentration. Experimental. Fentanyl was administered i.v. in an escalating fashion (2, 4, 8, 16 and 32 μg/kg bwt) at 10-min intervals. Blood samples were collected before and at selected times until 24 h post administration. Blood samples were analysed for fentanyl and metabolite concentrations and correlated with behavioural and physiological observations and selected blood analytes. Foals mostly appeared to be unaffected following 2 μg/kg bwt (1.09 ± 0.41 μg/l; average maximal plasma concentration) of fentanyl, but 6 of the 8 foals appeared to be sedated following 4 μg/kg bwt (3.07 ± 1.11 μg/l). Ataxia with increased locomotor activity, muscle rigidity and head pressing posture was observed in many foals at 8 (7.24 ± 3.22 μg/l) and 16 μg/kg bwt (17.4 ± 5.67 μg/l). All foals were heavily sedated after 32 μg/kg bwt (34.5 ± 10.3 μg/l); 3 of the 8 foals became recumbent. The average (± s.d.) terminal half-life following administration of the final dose was 44.2 ± 9.85 min. Behavioural and physiological responses to i.v. fentanyl in young foals are dose related. As with mature horses, the window of fentanyl plasma concentrations related to possible clinically desirable actions appears relatively narrow. © 2014 EVJ Ltd.

  4. The impact of orally administered phages on host immune response and surrounding microbial communities.

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    Hong, Yingying; Thimmapuram, Jyothi; Zhang, Jiayi; Collings, Clayton K; Bhide, Ketaki; Schmidt, Kyle; Ebner, Paul D

    2016-01-01

    Numerous studies have shown the efficacy of phage therapy in reducing foodborne pathogen carriage in food animals. Fewer studies have focused on host reactions, especially in terms of phage-mediated acute immune responses and effects on the gut microbiome. Here we administered E. coli O157:H7 phages in low (single dose of 105 PFU) or high (single dose of 107 PFU) quantities to mice. While there were time points at which cytokine levels in different treatment groups differed from one another, all cytokine levels remained within normal ranges for mice regardless of treatment. Similarly, the patterns of these differences were not dose related, indicating that phage treatment did not result in a strong acute immune response as measured here. In separate experiments, 3-week-old pigs received a diet containing an in-feed antibiotic or daily phage treatment. After two weeks, microbial DNA of ileal, cecal, and fecal contents was characterized using 16S rRNA sequencing. There were no statistical differences in performance among the different groups. Compared to control pigs (no antibiotic, no phage), antibiotic treatment significantly altered ileal microbiome composition (P < 0.05), with Bacilli being most affected (antibiotic treated: 22%; control: 76%; FDR = 0.0572). No significant differences were observed in cecal and fecal microbiome composition between antibiotic-treated and control pigs, and there were no differences in gut microbiome composition between phage treated and control pigs in any intestinal compartment. Significant abundance differences were observed at the OTU level, with OTUs belonging to genera such as Lactobacillus and Streptococcus being over- or under-represented in either antibiotic or phage treated groups compared to control pigs. Determining whether these changes are deleterious to host, however, requires further study.

  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. Parents' understanding of and accuracy in using measuring devices to administer liquid oral pain medication.

    Science.gov (United States)

    Tanner, Shauna; Wells, Martha; Scarbecz, Mark; McCann, Billy W

    2014-02-01

    Dentists recommend over-the-counter medications for postoperative pain in children, and parents often make dosing errors when administering these medications. The authors compared the dosing accuracy when parents used various measuring devices and aimed to identify risk factors associated with dosing errors. The authors recruited parent-child pairs visiting the Pediatric Clinic at the College of Dentistry at The University of Tennessee Health Science Center, Memphis, and three private dental offices. The parents completed a survey and a liquid measuring exercise. The authors instructed parents to measure 5 milliliters of liquid by using a medicine cup with clear markings, a medicine cup with printed markings, a cylindrical measuring spoon and an oral syringe. For the medicine cup with printed markings, the authors placed the parents randomly into one of two groups: those receiving text-only instructions or those receiving text-pictogram instructions. The authors weighed each device before and after the measuring exercise and compared the difference in weight with a reference weight of 5 mL. A total of 120 parent-child pairs participated. The results of a McNemar test revealed a significant difference in parents' ability to measure accurate doses with the various devices. The results of a Pearson χ(2) test showed no statistically significant difference between the control and study groups for dosing accuracy. The χ(2) analysis results showed no significant differences in risk factors that could be associated with dosing errors. Medicine cups were the devices parents reported using most frequently. Medicine cups had a higher occurrence of dosing errors when compared with the other devices. No sociodemographic factors were associated with dosing errors. Practical Implications. Dentists can improve pain management in pediatric patients by educating parents about accurate measuring devices, weight-based dosing and correct interpretation of medication dosing charts.

  7. Accuracy of Telehealth-Administered Measures to Screen Language in Spanish-Speaking Preschoolers.

    Science.gov (United States)

    Guiberson, Mark; Rodríguez, Barbara L; Zajacova, Anna

    2015-09-01

    There is a critical need for telehealth language screening measures for use with Spanish-speaking children because of the shortage of bilingual providers and the current lack of psychometrically sound measures that can be administered via telehealth. The purpose of the current study was to describe the classification accuracy of individual telehealth language screening measures as well as the accuracy of combinations of measures used with Spanish-speaking preschoolers from rural and underserved areas of the country. This study applied a hybrid telehealth approach that implemented synchronous videoconferencing, videocasting, and traditional pen and paper measures. Screening measures included a processing efficiency measure (Spanish nonword repetition [NWR]), language sampling, and a developmental language questionnaire. Eighty-two mostly Spanish-speaking preschool-age children and their parents participated. Thirty-four children had language impairment (LI), and 48 had typical language development. Although many of the individual measures were significantly associated with standardized language scores (r=0.27-0.55), not one of the measures had classification values of 0.8 or higher, which is recommended when screening for LI. However, when NWR scores were combined with language sample or parent survey measures, promising classification accuracy values that approached or were higher than 0.8 were obtained. This research provides preliminary evidence showing the effectiveness of a hybrid telehealth model in screening the language development of Spanish-speaking children. A processing efficiency measure, NWR, combined with a parent survey or language sample measure can provide informative and accurate diagnostic information when screening Spanish-speaking preschool-age children for LI.

  8. Development of Orally Administered γ-Tocotrienol (GT3) Nanoemulsion for Radioprotection.

    Science.gov (United States)

    Ledet, Grace A; Biswas, Shukla; Kumar, Vidya P; Graves, Richard A; Mitchner, Demaurian M; Parker, Taylor M; Bostanian, Levon A; Ghosh, Sanchita P; Mandal, Tarun K

    2016-12-24

    The purpose of this study was two-fold: (1) to formulate γ-tocotrienol (GT3) in a nanoemulsion formulation as a prophylactic orally administered radioprotective agent; and (2) to optimize the storage conditions to preserve the structural integrity of both the formulation and the compound. γ-tocotrienol was incorporated into a nanoemulsion and lyophilized with lactose. Ultra performance liquid chromatography-mass spectroscopy (UPLC-MS) was used to monitor the chemical stability of GT3 over time, the particle size and ζ potential, and scanning electron microscopy (SEM) were used to study the physical stability of the nanoemulsion. Radioprotective and toxicity studies were performed in mice. The liquid formulation exhibited GT3 degradation at all storage temperatures. Lyophilization, in the presence of lactose, significantly reduced GT3 degradation. Both the liquid and lyophilized nanoemulsions had stable particle size and ζ potential when stored at 4 °C. Toxicity studies of the nanoemulsion resulted in no observable toxicity in mice at an oral dose of 600 mg/kg GT3. The nano-formulated GT3 (300 mg/kg) demonstrated enhanced survival efficacy compared to GT3 alone (200 and 400 mg/kg) in CD2F1 mice exposed to total body gamma radiation. The optimal long-term storage of formulated GT3 is as a powder at -20 °C to preserve drug and formulation integrity. Formulation of GT3 as a nanoemulsion for oral delivery as a prophylactic radioprotectant shows promise and warrants further investigation.

  9. 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.

  10. Pharmacokinetics of desmopressin administered as tablet and oral lyophilisate formulation in children with monosymptomatic nocturnal enuresis.

    Science.gov (United States)

    De Bruyne, Pauline; De Guchtenaere, Ann; Van Herzeele, Charlotte; Raes, Ann; Dehoorne, Jo; Hoebeke, Piet; Van Laecke, Erik; Vande Walle, Johan

    2014-02-01

    Desmopressin 120 μg oral lyophilisate and 200 μg tablet are considered bioequivalent, based on extrapolation of studies in a limited number of adults and on one dose-finding study of desmopressin oral lyophilisate in children. However, no comparative pharmacokinetic study in children was executed confirming this statement. No data are available on the influence of food intake on the bioavailability of desmopressin tablet in a pediatric setting, although studies in adults have documented that food intake results in a significantly lower desmopressin plasma concentration. In this study, we analyzed plasma concentrations of desmopressin oral lyophilisate and tablet with concomitant food intake. Twenty-three children with monosymptomatic nocturnal enuresis (mean age, 12.7 years) were recruited. Two tests were performed on two separate days in identical conditions with a standardized food and fluid intake. Desmopressin was administered as desmopressin tablet or desmopressin oral lyophilisate immediately after a meal. Desmopressin plasma concentration was measured at 1 h, 2 h, and 6 h postdosing. No significant difference in plasma concentration of 120 μg desmopressin oral lyophilisate and 200 μg tablet was demonstrated, even with concomitant food intake. A significant difference in variability was found, identifying a smaller variance for desmopressin oral lyophilisate plasma concentrations at all time points. This study demonstrates comparable plasma levels for desmopressin oral lyophilisate, despite the lower dose. The dosage for desmopressin oral lyophilisate is more predictable due to the significantly smaller variance. Therefore, desmopressin oral lyophilisate seems more suitable, especially in the younger age group for which time interval between dinner and drug administration is limited.

  11. Effect of instruction on the ability to use a self-administered epinephrine injector.

    Science.gov (United States)

    Segal, Nirit; Garty, Ben-Zion; Hoffer, Vered; Levy, Yael

    2012-01-01

    Patients with allergy as well as their parents frequently fail to use the self-administered epinephrine injection (EpiPen) properly in cases of allergic emergencies. To determine the benefit of an instruction session with follow-up instruction. We evaluated 141 patients aged 1.9-23.4 years (median 5.8 years, 83% with food allergy) or their parents (for those aged EpiPen during the first diagnostic visit to the allergy clinic during 2006-2009. At the next follow-up visit, the patients or their parents were asked to list the indications for epinephrine administration and to demonstrate the five steps involved in using the EpiPen. Each step was scored on a scale of 0-2. Fourteen participants (9.9%) had used self-injectable epinephrine in the past. Only 65 (46%) brought the device with them to the follow-up visit. The mean total score for the whole sample was 4.03 +/- 3. Fifty-three participants (38%) failed to remove the cap before trying to apply the device. Only 8 (5.6%) had a maximum score. The patients and their parents were reinstructed in the use of the device: 41 participants were reexamined at a subsequent follow-up visit after 1.02 +/- 0.56 years; their mean score improved from 4.71 +/- 3.04 to 6.73 +/- 3.18 (P EpiPen after only one instruction session with a specialist. Repeated instruction may improve the results and we therefore recommend that the instructions be repeated at every follow-up visit.

  12. Developmental defects of coronary vasculature in rat embryos administered bis-diamine.

    Science.gov (United States)

    Hanato, Takashi; Nakagawa, Masao; Okamoto, Nobuhiko; Nishijima, Setsuko; Fujino, Hidetoshi; Shimada, Morimi; Takeuchi, Yoshihiro; Imanaka-Yoshida, Kyoko

    2011-02-01

    Conotruncal anomalies are often associated with abnormal coronary arteries. Although bis-diamine is known to induce conotruncal defects, its pathological effects on coronary vascular development have not been demonstrated. This study sought to assess the teratogenic effects of bis-diamine on coronary vascular development and the pathogenesis of this anomalous association. A single 200 mg dose of bis-diamine was administered to pregnant Wistar rats at 10.5 days of gestation. Fifty-two embryos from 10 mother rats underwent morphological analysis of the coronary arteries. Three embryos each were removed from four mothers on embryonic days (ED) 14.5, 15.5, 16.5, and 17.5 and used for immunohistochemical studies using the anti-vascular cell adhesion molecule (VCAM)-1 antibody. Conotruncal anomalies were detected in 48 of 52 embryos, and an aplastic or hypoplastic left coronary artery was found in all of them. In control embryos at ED 16.5, VCAM-1-positive epicardial cells were transformed into mesenchymal cells in vascular plexus, which appeared to differentiate into the endothelial cells of coronary vasculature. In the heart at ED 17.5, coronary vasculature was well developed and connected with coronary ostia near the aorta. However, poor epicardial-mesenchymal transformation and subsequent differentiation was revealed in bis-diamine-treated embryos at EDs 16.5 and 17.5, causing abnormal development of the coronary vasculature and incomplete connections with coronary ostia of the aorta. Anomalous coronary arteries in the bis-diamine-treated embryos are induced by the disruption of epicardial-mesenchymal transformation and subsequent poor development of coronary vasculature. Incomplete hatching of the coronary ostium is associated with abnormal truncal division. © 2010 Wiley-Liss, Inc.

  13. 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

  14. Tissue distribution and toxicity of intravenously administered titanium dioxide nanoparticles in rats.

    Science.gov (United States)

    Fabian, Eric; Landsiedel, Robert; Ma-Hock, Lan; Wiench, Karin; Wohlleben, Wendel; van Ravenzwaay, Ben

    2008-03-01

    The tissue distribution and toxicity of intravenously administered nanoparticles of titanium dioxide (TiO2) (>10 wt.% at nanoparticle in a situation of 100% bioavailability. Male Wistar rats were treated with single intravenous injections of a suspension of TiO2 in serum (5 mg/kg body weight), and the tissue content of TiO2 was determined 1, 14, and 28 days later. Biochemical parameters and antigens in serum were also assessed to determine potential pathological changes. The health and behavior of the animals were normal throughout the study. There were no detectable levels of TiO2 in blood cells, plasma, brain, or lymph nodes. The TiO2 levels were highest in the liver, followed in decreasing order by the levels in the spleen, lung, and kidney, and highest on day 1 in all organs. TiO2 levels were retained in the liver for 28 days, there was a slight decrease in TiO2 levels from day 1 to days 14 and 28 in the spleen, and a return to control levels by day 14 in the lung and kidney. There were no changes in the cytokines and enzymes measured in blood samples, indicating that there was no detectable inflammatory response or organ toxicity. Overall, rats exposed to TiO2 nanoparticles by a route that allows immediate systemic availability showed expected tissue distribution, no obvious toxic health effects, no immune response, and no change in organ function. Therefore, even with 100% bioavailability of the 5 mg/kg TiO2 dose afforded by the intravenous route of administration, there were no remarkable toxic effects evident in the experimental animals. These results indicate that TiO2 nanoparticles could be used safely in low doses.

  15. Tissue distribution and clearance of intravenously administered titanium dioxide (TiO2) nanoparticles.

    Science.gov (United States)

    Shinohara, Naohide; Danno, Nobuko; Ichinose, Takayuki; Sasaki, Takeshi; Fukui, Hiroko; Honda, Kazumasa; Gamo, Masashi

    2014-03-01

    The organ-tissue distribution and clearance of Degussa P25 TiO2 nanoparticles were determined after intravenous administration to rats (0.95 mg/kg bodyweight) using an inductively coupled plasma sector field mass spectrometer. The detection limits of Ti analysis, 0.54 and 1.4 ng/mL for blood and urine and 0.35-2.0 ng/g tissue for several organ tissues, enabled determination of tissue distribution and clearance for organs in which Ti content could not be previously determined due to low concentrations. Blood concentrations of TiO2 were 420 and 19 ng/mL at 5 and 15 min after administration, which were equivalent of only 2.8% and 0.13% of the administration dose, respectively. At 6 h, 94%, 2.0%, 0.17%, 0.023%, 0.014% and 0.026% of administered TiO2 was found in the liver, spleen, lung, kidney, heart and blood, respectively. Liver and spleen TiO2 burden was significantly higher in the administration than control group (p TiO2 burden in the lung, kidney, heart and blood decreased over time. A two-step decay model was more suitable than a one-step decay model for the decay curves of pulmonary TiO2 burden but did not improve fitting to the decay curves of kidney TiO2 burden. No translocation to the brain was confirmed at a lower detection limit than was applied in previous studies. Ti content in faeces and urine in the TiO2 administration group did not differ from that in the control group.

  16. Cisplatin can be safely administered to ovarian cancer patients with hypersensitivity to carboplatin.

    Science.gov (United States)

    Bergamini, A; Pisano, C; Di Napoli, M; Arenare, L; Della Pepa, C; Tambaro, R; Facchini, G; Gargiulo, P; Rossetti, S; Mangili, G; Pignata, S; Cecere, S C

    2017-01-01

    Hypersensitivity reactions (HSR) are frequently reported in patients rechallenged with carboplatin for recurrent ovarian cancer (ROC) and represent a critical issue, since discontinuation of the platinum-based therapy could affect prognosis. Several strategies to allow platinum rechallenge have been described, with controversial outcomes. The aim of this study is to illustrate a 10-year experience with cisplatin in patients with a previous HSR to carboplatin or at risk for allergy. A retrospective review of all patients with platinum sensitive ROC retreated with carboplatin was performed between January 2007 and May 2016 at the Istituto Nazionale Tumori, Fondazione "G. Pascale", Naples. Among 183 patients, 49 (26.8%) presented HSR to carboplatin, mainly during second line therapy. Mean number of cycles before HSR was 8 (range 3-17). G2, G3 and G4 reaction were detected in 83%, 15% and 2% of patients, respectively. In a multivariate analysis including age, hystotype, BRCA status, previous known HSR, and combination drug administered, only the type of carboplatin-based doublet used as 2nd line therapy was found to significantly affect HSR development, with a protective effect of PLD (pegylated liposomal doxorubicin) (p = 0.014, OR = 0.027). Thirty seven patients (77%) with a previous HSR to carboplatin were rechallenged with cisplatin. Treatment was generally well tolerated. 5 patients (13.1%) experienced mild HSR to cisplatin, successfully managed in all cases. 14 patients were treated with cisplatin even without a carboplatin-related HSR due to other allergies. Among these, only one developed HSR (7.1%). Cisplatin rechallenge is a feasible approach in patients experiencing HSR to carboplatin to maintain the beneficial effect of platinum while reducing hypersensitivity-related risks. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Influence of caffeine administered at 45 °C on bone tissue development

    Directory of Open Access Journals (Sweden)

    Marek Tomaszewski

    2014-11-01

    Full Text Available [b]introduction and objective[/b]. Caffeine is one of the world’s most commonly ingested alkaloids which easily permeates the placenta. The teratogenic and embryotoxic influence of large doses of caffeine has been established in many experimental studies on animals. The objective of this work was to assess the influence of caffeine, administered at 45 °C, on the development of the bone tissue of rats, with particular reference to elemental bone composition using an X-ray microprobe. [b]materials and methods[/b]. The research was conducted on white rats of the Wistar strain. The fertilized females were divided into two groups: an Experimental Group (Group E and a Control Group (Group C. The females in Group E were given caffeine orally (at 45 °C in 30 mg/day doses from the 8 [sup]th [/sup] to the 21 [sup]st[/sup] day of pregnancy. The females in Group C were given water at the same temperature. The fetuses were used to assess the growth and mineralization of the skeleton. A qualitative analysis of the morphology and mineralization of bones was conducted using the alcian-alizarin method. For calcium and potassium analysis, an X-ray microprobe was used. [b]results.[/b] By staining the skeleton using the alcian-alizarin method, changes in 52 of Group E fetuses were observed. The frequency of the development variants in the Group E rats was statistically higher, compared with Group C. [b]conclusions[/b]. Receiving caffeine at a higher temperature may result in different pharmacodynamics and significantly change tolerance to it. In Group E, a significant decrease in the calcium level, as well as an increase in the potassium level, was observed. The X-ray microprobe can be a perfect complement to the methods which enable determination of the mineralization of osseous tissue.

  18. Safety and efficacy of administering the maximal dose of candesartan in renal transplant recipients.

    Science.gov (United States)

    Okumi, Masayoshi; Kawada, Noritaka; Ichimaru, Naotsugu; Kitamura, Harumi; Abe, Toyofumi; Imamura, Ryoichi; Kojima, Yasuyuki; Kokado, Yukito; Isaka, Yoshitaka; Rakugi, Hiromi; Nonomura, Norio; Moriyama, Toshiki; Takahara, Shiro

    2011-12-01

    The regular dose of an angiotensin II type-1 receptor blocker (ARB) in renal transplant patients for hypertension is shown to be safe and effective; however, information on the appropriate dosing of ARBs in renal transplant patients is limited. We evaluate the efficacy and safety of the maximal dose of candesartan administered to renal transplant patients. Sixty-nine recipients were enrolled in this study. Patients were divided into three groups based on the basal dose of candesartan: patients not taking candesartan (Group A); patients taking a low to medium dose of candesartan (2-4 mg/day; Group B); and patients taking a high dose of candesartan (8 mg/day; Group C). During the course of the study, the dose of candesartan was gradually increased to a final dose of 12 mg/day. Physiological and biochemical parameters were measured before and after the 12-month study period. Ninety-one percent of patients succeeded in continuing their administration of candesartan for 1 year and 75% tolerated the administration of the maximal dose of candesartan. Significant differences in proteinuria, albuminuria, serum creatinine, and estimated glomerular filtration rate (eGFR) level among the groups were detected. In Group A, candesartan reduced systolic blood pressure, decreased the levels of proteinuria, albuminuria, eGFR, and hemoglobin and increased plasma potassium, creatinine level, and plasma renin activity. The gradual increase of an ARB to its maximal dose in renal transplant patients is safe when carefully monitored. We were able to demonstrate the impact of maximal renin-angiotensin system (RAS) blockade on both proteinuria and albuminuria, which indicates the need for future, long-term randomized prospective trials to further establish the impact of maximal RAS blockade on renal and cardiovascular protection in transplant patients.

  19. Long-lived effects of administering β-glucans: Indications for trained immunity in fish.

    Science.gov (United States)

    Petit, Jules; Wiegertjes, Geert F

    2016-11-01

    Over the past decades, it has become evident that immune-modulation of fish with β-glucans, using injection, dietary or even immersion routes of administration, has stimulating but presumed short-lived effects on both intestinal and systemic immunity and can increase protection against a subsequent pathogenic challenge. Although the exact effects can be variable depending on, among others, fish species and administration route, the immune-stimulating effects of β-glucans on the immune system of fish appear to be universal. This review provides a condensed update of the most recent literature describing the effects of β-glucans on the teleost fish immune system. We shortly discuss possible mechanisms influencing immune-stimulation by β-glucans, including microbial composition of the gut, receptor recognition and downstream signalling. Of interest, in mammalian monocytes, β-glucans are potent inducers of trained immunity. First, we screened the literature for indications of this phenomenon in fish. Criteria that we applied include indications for at least one out of three features considered characteristic of trained immunity; (i) providing protection against a secondary infection in a T- and B-lymphocyte independent manner, (ii) conferring increased resistance upon re-infection and, (iii) relying on key roles for innate immune cell types such as natural killer cells and macrophages. We conclude that several indications exist that support the notion that the innate immune system of teleost fish can be trained. Second, we screened the literature for indications of long-lived effects on innate immunity of fish after administering β-glucans, a criterion which could help to identify key roles for macrophages on resistance to infection. We discuss whether β-glucans, as well-known immune-stimulants, are able to train the immune system of fish and argue in favour of further studies designed to specifically investigate this phenomenon in fish. Copyright © 2016 The

  20. Phase I dose-finding study of cabazitaxel administered weekly in patients with advanced solid tumours

    Science.gov (United States)

    2013-01-01

    Background 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. Methods 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. Results Thirty-one patients were enrolled. Two of six patients experienced DLTs at 12 mg/m2, 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 Cmax and AUC0–t were dose proportional for the 6–12 mg/m2 doses. Conclusion The MTD of weekly cabazitaxel was 12 mg/m2 and the recommended weekly dose was 10 mg/m2. The observed safety profile and antitumour activity of cabazitaxel were consistent with those observed with other taxanes in similar dosing regimens. Trial registration The study was registered with ClinicalTrials.gov as NCT01755390. PMID:24099585