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Sample records for sch23390 caused substantial

  1. Comparison between dopamine-stimulated adenylate cyclase and 3H-SCH 23390 binding in rat striatum

    International Nuclear Information System (INIS)

    Andersen, P.H.; Groenvald, F.C.; Jansen, J.A.

    1985-01-01

    Methods for measuring 3 H-SCH 23990 binding and dopamine (DA) stimulated adenylate cyclase (AC) were established in identical tissue preparations and under similar experimental conditions. Pharmacological characterization revealed that both assays involved interaction with the D1 receptor or closely associated sites. In order to investigate whether the binding sites for 3 H-SCH 23390 and DA in fact are identical, the antagonistic effects of a variety of pharmacologically active compounds were examined. Surprisingly, the K/sub i/-values obtained from Schild-plot analysis of the antagonism of DA-stimulated AC, were 80-240 times higher than the K/sub i/-values obtained from competition curves of 3 H-SCH 23390 binding. Since both assays were performed under identical conditions, the differences in K/sub i/-values indicate the possibility of different binding sites for DA and 3 H-SCH 23390 or, that DA and 3 -SCH 23390 label different states of the same receptor. 19 references, 7 figures, 2 tables

  2. Synthesis of 11C-SCH 23390, a dopamine D-1 receptor antagonist, for use in in vivo receptor binding studies with PET

    International Nuclear Information System (INIS)

    Halldin, Christer; Stone-Elander, Sharon; Farde, Lars; Ehrin, Erling; Fasth, Karl-Johan; Langstroem, Bengt; Sedvall, Goeran; Karolinska Hospital, Stockholm; Uppsala Univ.

    1986-01-01

    Central dopamine receptors are generally accepted to exist in at least two distinct subtypes: D-1 and D-2. Recently a benzazepine, SCH 23390, was reported to be a selective D-1 dopaminergic antagonist. PET studies of the radio-brominated 76 Br-SCH 23390 reported by Friedman, et al. indicated that the analog exhibits specific binding in the striatum of the monkey brain. Here we report the synthesis of 11 C-SCH 23390 suitable for the in vivo study of dopamine D-1 receptors in the human brain. (author)

  3. In vivo binding of a radioiodinated derivative of SCH 23390 (SCH)

    International Nuclear Information System (INIS)

    McQuade, R.D.; Iorio, L.C.; Chipkin, R.E.; Barnett, A.

    1986-01-01

    The in vitro binding properties of SCH have been extensively characterized, however, little research has been conducted on its in vivo binding profile. This report is on the characterization of the in vivo binding of 7- 125 I-SCH (71 SCH), which possesses a specific radioactivity of 2200 Ci/mmole and exhibits in vitro binding properties similar to those of 3 H-SCH. Sprague-Dawley rats were injected with 0.02 nmoles of 7ISH, in the absence and presence of 30 nmoles of unlabeled SCH, and were sacrificed at 1,2 and 4 hours post-treatment. The striatum and cerebellum were removed, weighed and the radioactivity was counted. Specific binding was defined as cpm in the absence of SCH less cpm in the presence of SCH. One hour after injection, the striatum of the rats treated with 7ISCH contained 170,000 cpm/g tissue, of which 105,000 cpm/g tissue were specific. The cerebellum of the rats contained 75% fewer cpm/g tissue and did not exhibit specifically bound in the striatum, but not in the cerebellum. Sacrifice after longer periods of time resulted in a 35% decrease in specific binding between 1 and 2 h, and a 70% decrease between 1 and 4 h. The pharmacological profile of the in vivo binding of 7ISCH was determined by the ability of dopaminergic antagonists to inhibit specific binding in the rat striatum 1 h after treatment. Thirty nmoles of SCH caused a 55% inhibition of the specific binding to striatum, while an equal amount of SCH 23388, the inactive S isomer of SCH, resulted in no inhibition. Haloperidol, a D-2 antagonist, did not inhibit the specific binding of 7ISCH to the striatum at doses up to 3000 nmoles. These data indicate that 7ISCH is specifically bound, in vivo, to D-1 receptors in the rat striatum

  4. Enantiomeric analogues of SCH 23390 as new probes for behavioral interactions between D-1 and D-2 dopaminergic function

    International Nuclear Information System (INIS)

    Waddington, J.L.; Mashurano, M.; Molloy, A.G.; O'Boyle, K.M.

    1986-01-01

    The purposes of this article are to describe the properties of some newer selective D 1 agents, and to characterize behavioral responses to a D 1 agonist in the intact adult rat. R- and S-SKandF 83566 and other new 1-phenyl-1H-3-benzazephines as selective D 1 agents are discussed. The displacement of 3 H-SCH 23390 from human brain D 1 receptors, in comparison with displacement of 3 H-piflutixol and 3 H-spiperone is shown. Enantiomeric induction of grooming and other behaviors by R- and S-SKandF 38393 is examined. Sections are also devoted to pharmacological characterization of behavioral responses to SKandF 38393 and to D 1 : D 2 receptor systems and the regulation of dopaminergic behaviors

  5. Effect of the dopamine D1-like receptor antagonist SCH 23390 on the microstructure of ingestive behaviour in water-deprived rats licking for water and NaCl solutions.

    Science.gov (United States)

    Galistu, Adriana; D'Aquila, Paolo S

    2012-01-18

    The analysis of licking microstructure provides measures, size and number of licking bouts, which might reveal, respectively, reward evaluation and behavioural activation. Based on the different effects of the dopamine D1-like and D2-like receptor antagonists SCH 23390 and raclopride on licking for sucrose, in particular the failure of the former to reduce bout size and the ability of the latter to induce a within-session decrement of bout number resembling either reward devaluation or neuroleptics on instrumental responding, we suggested that activation of reward-associated responses depends on dopamine D1-like receptor stimulation, and its level is updated on the basis of a dopamine D2-like receptor-mediated reward evaluation. Consistent results were obtained in a study examining the effect of dopamine D2-like receptor antagonism in rats licking for NaCl solutions and water. In this study, we examined the effects of the dopamine D1-like receptor antagonist SCH 23390 (0, 10, 20 and 40 μg/kg) on the microstructure of licking for water and sodium chloride solutions (0.075 M, 0.15 M, 0.3 M) in 12 h water deprived rats. Rats were exposed to each solution for 60 s either after the first lick or after 3 min that the animals were placed in the chambers. Bout size, but not bout number, was decreased at the highest NaCl concentration. SCH 23390 produced a decrease of bout number and of lick number mainly due to the decreased number of subjects engaging in licking behaviour, and failed to reduce bout size for Na Cl and water at a dose which increased the latency to the 1st lick but did not affect the intra-bout lick rate. In agreement with previous observations, these results suggest that dopamine D1-like receptors play an important role in the activation of reward-oriented responses. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. The disruptive effects of methamphetamine on delayed-matching-to-sample performance reflect proactive interference and are reduced by SCH23390.

    Science.gov (United States)

    Macaskill, Anne C; Harrow, Catherine C; Harper, David N

    2015-01-01

    Different drugs produce different patterns of impairment on delayed matching-to-sample tasks. For example, (+/-)3,4-methylenedioxymethamphetamine (MDMA) produces an increase in proactive interference. That is, subjects are less accurate when they are required to make a response different to the one they made on the immediately previous trial. The current study assessed whether methamphetamine also produces this particular pattern of disruption in delayed matching-to-sample performance in rats. Methamphetamine primarily reduced accuracy on trials where the correct response differed from the one made on the previous trial. Thus methamphetamine, like MDMA and other stimulant-based drugs of abuse, increased proactive interference. This impairment was reduced by prior administration of the dopamine D1 antagonist SCH23390. These results further extend a general conclusion that a range of stimulant-based drugs may disrupt working memory function indirectly via a tendency to repeat previously made responses and that this disruption is related to D1 receptor activity. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Dopamine1 receptors in rat kidneys identified with 125I-Sch 23982

    International Nuclear Information System (INIS)

    Felder, R.A.; Jose, P.A.

    1988-01-01

    Dopamine1 receptors were studied in rat kidney using the selective dopamine1 antagonist 125I-labeled Sch 23982. The specific binding of 125I-Sch 23982 (defined by 5 microM Sch 23390) to renal cortical homogenates incubated at room temperature was rapid, saturable with time and ligand concentration, and reversible. Analysis of Rosenthal plots revealed a single class of receptors with an apparent dissociation constant of 12.2 +/- 1.9 nM and maximum receptor density of 1.03 +/- 0.15 pmol/mg protein (n = 6). However, competition experiments with the dopamine1 antagonist Sch 23390 revealed a low- and high-affinity binding site with inhibition constants of 1 x 10(-6) and 1 x 10(-8) M, respectively. The competition experiments were also indicative of dopamine1 receptors with stereoselectivity noted for dopamine1 but not for dopamine2 antagonists. The inhibition constants for dopamine1 antagonists and agonists were two orders of magnitude greater in renal cortical than striatal homogenates. Different buffers affected striatal but not renal cortical binding. Autoradiographic studies revealed 125I-Sch 23982 binding in renal cortical but not medullary tissue. These studies confirm the presence of dopamine1 receptors in the cortex of the rat kidney

  8. Central actions of a novel and selective dopamine antagonist

    International Nuclear Information System (INIS)

    Schulz, D.W.

    1985-01-01

    Receptors for the neurotransmitter dopamine traditionally have been divided into two subgroups: the D 1 class, which is linked to the stimulation of adenylate cyclase-activity, and the D 2 class which is not. There is much evidence suggesting that it is the D 2 class which is not. There is much evidence suggesting that it is the D 2 dopamine receptor that mediates the physiological and behavioral actions of dopamine in the intact animal. However, the benzazepine SCH23390 is a dopamine antagonist which has potent behavioral actions while displaying apparent neurochemical selectivity for the D 1 class of dopamine receptors. The purpose of this dissertation was to (1) confirm and characterize this selectivity, and (2) test certain hypothesis related to possible modes of action of SCH233390. The inhibition of adenylate cyclase by SCH23390 occurred via an action at the dopamine receptor only. A radiolabeled analog of SCH23390 displayed the receptor binding properties of a specific high-affinity ligand, and regional receptor densities were highly correlated with dopamine levels. The subcellular distribution of [ 3 H]-SCH23390 binding did not correspond completely with that of dopamine-stimulated adenylate cyclase. The neurochemical potency of SCH23390 as a D 1 receptor antagonist was preserved following parental administration. A variety of dopamine agonists and antagonists displayed a high correlation between their abilities to compete for [ 3 H]-SCH23390 binding in vitro and to act at an adenylate cyclase-linked receptor. Finally, the relative affinities of dopamine and SCH23390 for both D 1 receptors and [ 3 H]-SCH23390 binding sites were comparable. It is concluded that the behavioral effects of SCH23390 are mediated by actions at D 1 dopamine receptors only, and that the physiological importance of this class of receptors should be reevaluated

  9. Benzazepines: Structure-activity relationships between D1 receptor blockade and selected pharmacological effects

    International Nuclear Information System (INIS)

    Iorio, L.C.; Billiard, W.; Gold, E.H.

    1986-01-01

    This chapter describes the displacement of 3 H-23390 and 3 H-spiperone binding by dopamine agonists and antagonists. The authors undertook an evaluation of the ability of selected analogs of SCH 23390 to displace 3 H-SCH 23390 and 3 H-spiperone. Structure-activity relationships of SCH 23390 analogs: 7-position substituents, is shown. It is shown that, in general, benzazepines with a variety of substituents in the 7-position retain their selectivity for D 1 sites. Substituents at the 8-position and at the N-position are also discussed. The authors determine a correlation between displacement of 3 H-SCH 23390 and blockade of dopamine-sensitive adenylate cyclase (DSAC). These effects and inhibition of conditioned avoidance responsing (CAS) in rats was also studied. A detailed evaluation is presented of the effects of SCH 23390 and haloperidol in the Inclined Screen and CAR tests

  10. Pharmacological and biochemical characterization of the D-1 dopamine receptor mediating acetylcholine release in rabbit retina

    International Nuclear Information System (INIS)

    Hensler, J.G.; Cotterell, D.J.; Dubocovich, M.L.

    1987-01-01

    Superfusion with dopamine (0.1 microM-10 mM) evokes calcium-dependent [ 3 H]acetylcholine release from rabbit retina labeled in vitro with [ 3 H]choline. This effect is antagonized by the D-1 dopamine receptor antagonist SCH 23390. Activation or blockade of D-2 dopamine, alpha-2 or beta receptors did not stimulate or attenuate the release of [ 3 H]acetylcholine from rabbit retina. Dopamine receptor agonists evoke the release of [ 3 H]acetylcholine with the following order of potency: apomorphine ≤ SKF(R)82526 3 H]acetylcholine: SCH 23390 (IC50 = 1 nM) 3 H]acetylcholine release is characteristic of the D-1 dopamine receptor. These potencies were correlated with the potencies of dopamine receptor agonists and antagonists at the D-1 dopamine receptor in rabbit retina as labeled by [ 3 H]SCH 23390, or as determined by adenylate cyclase activity. [ 3 H]SCH 23390 binding in rabbit retinal membranes was stable, saturable and reversible. Scatchard analysis of [ 3 H]SCH 23390 saturation data revealed a single high affinity binding site (Kd = 0.175 +/- 0.002 nM) with a maximum binding of 482 +/- 12 fmol/mg of protein. The potencies of dopamine receptor agonists to stimulate [ 3 H]acetylcholine release were correlated with their potencies to stimulate adenylate cyclase (r = 0.784, P less than .05, n = 7) and with their affinities at [ 3 H]SCH 23390 binding sites (r = 0.755, P < .05, n = 8)

  11. The multiplicity of the D-1 dopamine receptor

    International Nuclear Information System (INIS)

    Mailman, R.B.; Klits, C.D.; Lewis, M.H.; Rollema, H.; Schulz, D.W.; Wyrick, S.

    1986-01-01

    The authors have sought to address two questions of some neuropharmacological importance in this chapter. First, they examine the nature of mechanisms by which dopamine initiates many psychopharmacological effects and, second, they study the possibility of designing highly specific drugs targeted only at a selected subpopulation of dopamine receptors. Effects of SCH23390 and haloperidol on concentrations of dopamine, DOPAC, and HVA in various rat brain regions are shown. In addition, the effects of SCH23390 on the in vivo binding of dipropyl-5, 6-ADTN are shown. Differential distribution of a dopamine sensitive adenylate cyclase and ( 3 H)-SCH23390 binding sites are examined. A model is presented of D 1 dopamine receptors in membrane, illustrating the lack of identity of some of the ( 3 H)-SCH23390 binding sites with the dopamine receptor linked to stimulation of cAMP synthesis

  12. Attenuation of antagonist-induced impairment of dopamine receptors by L-prolyl-L-leucyl-glycinamide

    International Nuclear Information System (INIS)

    Saleh, M.I.M.

    1988-01-01

    The present study was undertaken in order to determine whether chronic,long-term postnatal challenge of rat pups per se, with specific dopamine D1 and D2 receptor antagonists, would modify the ontogeny of the respective receptor types. Since the neuropeptide L-prolyl-L-leucyl-glycinamide (PLG) attenuates the effect of haloperidol on dopamine D2 receptors in adult rats it was of interest to determine whether PLG would modulate antagonists-induced alterations in the ontogeny of striatal dopamine D1 and D2 receptors. Half of the rats were treated daily for 32 days from birth with SCH-23390, a selective dopamine D1 antagonist; or spiroperidol, a selective dopamine D2 antagonists; or both SCH-23390 and spiroperidol; or saline. The other half of the litters were treated with PLG, in combination with the other treatments. Animals were decapitated at 5, 8, and 12 weeks from birth for neurochemical analysis of the striatum. Chronic SCH-23390 treatment produced a 70-80% decrease in the binding of [ 3 H] SCH-23390 to striatal homogenates. The alteration at 5 weeks was associated with a 78% decrease in the Bmax for [ 3 H] SCH-23390 binding, and no change in the K D . Similarly, at 5, 8, and 12 weeks, chronic spiroperidol treatment reduced the binding of [ 3 H] spiroperidol to striatal homogenates by 70-80%

  13. Photoaffinity labelling of high affinity dopamine binding proteins

    International Nuclear Information System (INIS)

    Ross, G.M.; McCarry, B.E.; Mishra, R.K.

    1986-01-01

    A photoactive analogue of the dopamine agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronapthalene (ADTN) has been synthesized and used to photoaffinity label dopamine binding proteins prepared from bovine caudate nucleus. N-(3-]N'-4-azidobenzamidol]-aminopropyl)-aminopropyl)-ADTN (AzB-AP-ADTN) was incubated with caudate membranes and irradiated with UV light. Membranes were then repeatedly washed by centrifugation to remove excess photolabel. A binding assay, using ( 3 H)-SCH 23390 (a D 1 specific antagonist), was then performed to evaluate the loss of receptor density in the photolyzed preparation. AzB-AP-ADTN irreversibly blocked ( 3 H)-SCH 23390 binding in a dose-dependent manner. Scatchard analysis revealed a decrease in the B/sub max/, with no significant change in the K/sub d/, of ( 3 H)-SCH 23390 binding. Compounds which compete for D 1 receptor binding (such as dopamine, SKF 38393 or apomorphine), proteted the SCH 23390 binding site from inactivation. This data would suggest that the novel photoaffinity ligand, AzB-AP-ADTN, can covalently label the D 1 (adenylate cyclase linked) dopamine receptor

  14. 6-hydroxydopamine-induced degeneration of nigral dopamine neurons: differential effect on nigral and striatal D-1 dopamine receptors

    International Nuclear Information System (INIS)

    Porceddu, M.L.; Giorgi, O.; De Montis, G.; Mele, S.; Cocco, L.; Ongini, E.; Biggio, G.

    1987-01-01

    Dopamine-sensitive adenylate cyclase and 3 H-SCH 23390 binding parameters were measured in the rat substantia nigra and striatum 15 days after the injection of 6-hydroxydopamine into the medial forebrain bundle. The activity of nigral dopamine-sensitive adenylate cyclase and the binding of 3 H-SCH 23390 to rat nigral D-1 dopamine receptors were markedly decreased after the lesion. On the contrary, 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine pathway enhanced both adenylate cyclase activity and the density of 3 H-SCH 23390 binding sites in striatal membrane preparations. The changes in 3 H-SCH 23390 binding found in both nigral and striatal membrane preparations were associated with changes in the total number of binding sites with no modifications in their apparent affinity. The results indicate that: a) within the substantia nigra a fraction (30%) of D-1 dopamine receptors coupled to the adenylate cyclase is located on cell bodies and and/or dendrites of dopaminergic neurons; b) striatal D-1 dopamine receptors are tonically innervated by nigrostriatal afferent fibers. 24 references, 1 figure, 1 table

  15. Possible involvement of dopamine D-1 and D-2 receptors in diazepam-induced hyperphagia in rats.

    Science.gov (United States)

    Naruse, T; Amano, H; Koizumi, Y

    1991-01-01

    Possible involvement of dopamine receptors in diazepam-induced (1 mg/kg, subcutaneous (sc] hyperphagia was studied in nondeprived rats. Pretreatment with the selective D-1 antagonist, SCH23390 (0.03 mg/kg, sc) inhibited diazepam-induced hyperphagia. In addition, pretreatment with the preferential D-2 antagonists, haloperidol (0.1 to 0.3 mg/kg, sc) and clebopride (0.1 to 0.3 mg/kg, sc) inhibited diazepam-induced hyperphagia in a dose-dependent manner. Pretreatment with co-administration of SCH23390 (0.1 mg/kg, sc) and clebopride (0.03 mg/kg, sc) completely inhibited this hyperphagia. The selective D-2 antagonist, sulpiride (40 mg/kg, sc) and the peripheral D-2 antagonist, domperidone (10 mg/kg, sc) did not affect diazepam-induced hyperphagia. However, sulpiride (10 micrograms, icv) or domperidone (2 micrograms, icv) administered centrally inhibited this hyperphagia. The highest dose of haloperidol (0.3 mg/kg, sc) or clebopride (0.3 mg/kg, sc) and higher doses of SCH23390 (0.01 and 0.03 mg/kg, sc) or SCH23390/clebopride (0.01/0.03 and 0.01/0.1 mg/kg, sc) tended to decrease spontaneous feeding in non-deprived rats. In addition, the highest dose of haloperidol, clebopride or SCH23390/clebopride inhibited spontaneous feeding in deprived rats. Interestingly, diazepam-induced hyperphagia was inhibited significantly by doses of haloperidol (0.1 mg/kg, sc), clebopride (0.1 mg/kg, sc) and SCH23390/clebopride (0.003/0.03 and 0.003/0.1 mg/kg, sc) which did not affect spontaneous feeding in non-deprived or deprived rats. Pretreatment with alpha-methyl-p-tyrosine (40 mg/kg, IP x 2, 6 and 2 h prior to diazepam administration) failed to inhibit this hyperphagia. Furthermore, pretreatment with a large dose of haloperidol (5 mg/kg, sc, 4 days before diazepam administration) augmented the sub-hyperphagic effect to diazepam (0.5 mg/kg, sc). Thus, these findings suggest that hyperphagia to diazepam is mediated in part by both dopamine D-1 and D-2 receptors in non-deprived rats.

  16. The anti-influenza drug oseltamivir evokes hypothermia in mice through dopamine D2 receptor activation via central actions

    Directory of Open Access Journals (Sweden)

    Akihiro Fukushima

    2018-01-01

    Full Text Available Oseltamivir has a hypothermic effect in mice when injected intraperitoneally (i.p. and intracerebroventricularly (i.c.v.. Here we show that the hypothermia evoked by i.c.v.-oseltamivir is inhibited by non-selective dopamine receptor antagonists (sulpiride and haloperidol and the D2-selective antagonist L-741,626, but not by D1/D5-selective and D3-selective antagonists (SCH-23390 and SB-277011-A, respectively. The hypothermic effect of i.p.-administered oseltamivir was not inhibited by sulpiride, haloperidol, L-741,626 and SCH-23390. In addition, neither sulpiride, haloperidol nor SCH-23390 blocked hypothermia evoked by i.c.v.-administered oseltamivir carboxylate (a hydrolyzed metabolite of oseltamivir. These results suggest that oseltamivir in the brain induces hypothermia through activation of dopamine D2 receptors.

  17. Relation of addiction genes to hypothalamic gene changes subserving genesis and gratification of a classic instinct, sodium appetite.

    Science.gov (United States)

    Liedtke, Wolfgang B; McKinley, Michael J; Walker, Lesley L; Zhang, Hao; Pfenning, Andreas R; Drago, John; Hochendoner, Sarah J; Hilton, Donald L; Lawrence, Andrew J; Denton, Derek A

    2011-07-26

    Sodium appetite is an instinct that involves avid specific intention. It is elicited by sodium deficiency, stress-evoked adrenocorticotropic hormone (ACTH), and reproduction. Genome-wide microarrays in sodium-deficient mice or after ACTH infusion showed up-regulation of hypothalamic genes, including dopamine- and cAMP-regulated neuronal phosphoprotein 32 kDa (DARPP-32), dopamine receptors-1 and -2, α-2C- adrenoceptor, and striatally enriched protein tyrosine phosphatase (STEP). Both DARPP-32 and neural plasticity regulator activity-regulated cytoskeleton associated protein (ARC) were up-regulated in lateral hypothalamic orexinergic neurons by sodium deficiency. Administration of dopamine D1 (SCH23390) and D2 receptor (raclopride) antagonists reduced gratification of sodium appetite triggered by sodium deficiency. SCH23390 was specific, having no effect on osmotic-induced water drinking, whereas raclopride also reduced water intake. D1 receptor KO mice had normal sodium appetite, indicating compensatory regulation. Appetite was insensitive to SCH23390, confirming the absence of off-target effects. Bilateral microinjection of SCH23390 (100 nM in 200 nL) into rats' lateral hypothalamus greatly reduced sodium appetite. Gene set enrichment analysis in hypothalami of mice with sodium appetite showed significant enrichment of gene sets previously linked to addiction (opiates and cocaine). This finding of concerted gene regulation was attenuated on gratification with perplexingly rapid kinetics of only 10 min, anteceding significant absorption of salt from the gut. Salt appetite and hedonic liking of salt taste have evolved over >100 million y (e.g., being present in Metatheria). Drugs causing pleasure and addiction are comparatively recent and likely reflect usurping of evolutionary ancient systems with high survival value by the gratification of contemporary hedonic indulgences. Our findings outline a molecular logic for instinctive behavior encoded by the brain with

  18. Link between D1 and D2 dopamine receptors is reduced in schizophrenia and Huntington diseased brain

    International Nuclear Information System (INIS)

    Seeman, P.; Niznik, H.B.; Guan, H.C.; Booth, G.; Ulpian, C.

    1989-01-01

    Dopamine receptor types D 1 and D 2 can oppose enhance each other's actions for electrical, biochemical, and psychomotor effects. The authors report a D 1 -D 2 interaction in homogenized tissue as revealed by ligand binding. D 2 agonists lowered the binding of [ 3 H]raclopride to D 2 receptors in striatal and anterior pituitary tissues. Pretreating the tissue with the D 1 -selective antagonist SCH 23390 prevented the agonist-induced decrease in [ 3 H]raclopride binding to D 2 sites in the striatum but not in the anterior pituitary, which has no D 1 receptors. Conversely, a dopamine-induced reduction in the binding of [ 3 H]SCH 23390 to D 1 receptors could be prevented by the D 2 -selective antagonist eticlopride. Receptor photolabeling experiments confirmed both these D 1 -D 2 interactions. The blocking effect by SCH 23390 was similar to that produced by a nonhydrolyzable guanine nucleotide analogue, and SCH 23390 reduced the number of agonist-labeled D 2 receptors in the high-affinity state. Thus, the D 1 -D 2 link may be mediated by guanine nucleotide-binding protein components. The link may underlie D 1 -D 2 interactions influencing behavior, since the link was missing in over half the postmortem striata from patients with schizophrenia and Huntington disease (both diseases that show some hyperdopamine signs) but was present in human control, Alzheimer, and Parkinson striata

  19. Dopamine D1 receptor activation maintains motor coordination and balance in rats.

    Science.gov (United States)

    Avila-Luna, Alberto; Gálvez-Rosas, Arturo; Durand-Rivera, Alfredo; Ramos-Languren, Laura-Elisa; Ríos, Camilo; Arias-Montaño, José-Antonio; Bueno-Nava, Antonio

    2018-02-01

    Dopamine (DA) modulates motor coordination, and its depletion, as in Parkinson's disease, produces motor impairment. The basal ganglia, cerebellum and cerebral cortex are interconnected, have functional roles in motor coordination, and possess dopamine D 1 receptors (D 1 Rs), which are expressed at a particularly high density in the basal ganglia. In this study, we examined whether the activation of D 1 Rs modulates motor coordination and balance in the rat using a beam-walking test that has previously been used to detect motor coordination deficits. The systemic administration of the D 1 R agonist SKF-38393 at 2, 3, or 4 mg/kg did not alter the beam-walking scores, but the subsequent administration of the D 1 R antagonist SCH-23390 at 1 mg/kg did produce deficits in motor coordination, which were reversed by the full agonist SKF-82958. The co-administration of SKF-38393 and SCH-23390 did not alter the beam-walking scores compared with the control group, but significantly prevented the increase in beam-walking scores induced by SCH-23390. The effect of the D 1 R agonist to prevent and reverse the effect of the D 1 R antagonist in beam-walking scores is an indicator that the function of D 1 Rs is necessary to maintain motor coordination and balance in rats. Our results support that D 1 Rs mediate the SCH-23390-induced deficit in motor coordination.

  20. A 3-lever discrimination procedure reveals differences in the subjective effects of low and high doses of MDMA.

    Science.gov (United States)

    Harper, David N; Langen, Anna-Lena; Schenk, Susan

    2014-01-01

    Drug discrimination studies have suggested that the subjective effects of low doses of (±)3,4-methylenedioxymethamphetamine (MDMA) are readily differentiated from those of d-amphetamine (AMPH) and that the discriminative stimulus properties are mediated by serotonergic and dopaminergic mechanisms, respectively. Previous studies, however, have primarily examined responses to doses that do not produce substantial increases in extracellular dopamine. The present study determined whether doses of MDMA that produce increases in synaptic dopamine would also produce subjective effects that were more like AMPH and were sensitive to pharmacological manipulation of D1-like receptors. A three-lever drug discrimination paradigm was used. Rats were trained to respond on different levers following saline, AMPH (0.5mg/kg, IP) or MDMA (1.5mg/kg, IP) injections. Generalization curves were generated for a range of different doses of both drugs and the effect of the D1-like antagonist, SCH23390 on the discriminative stimulus effects of different doses of MDMA was determined. Rats accurately discriminated MDMA, AMPH and saline. Low doses of MDMA produced almost exclusive responding on the MDMA lever but at doses of 3.0mg/kg MDMA or higher, responding shifted to the AMPH lever. The AMPH response produced by higher doses of MDMA was attenuated by pretreatment with SCH23390. The data suggest that low doses and higher doses of MDMA produce distinct discriminative stimuli. The shift to AMPH-like responding following administration of higher doses of MDMA, and the decrease in this response following administration of SCH23390 suggests a dopaminergic component to the subjective experience of MDMA at higher doses. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Chronic restraint stress causes a delayed increase in responding for palatable food cues during forced abstinence via a dopamine D1-like receptor-mediated mechanism.

    Science.gov (United States)

    Ball, Kevin T; Best, Olivia; Luo, Jonathan; Miller, Leah R

    2017-02-15

    Relapse to unhealthy eating habits in dieters is often triggered by stress. Animal models, moreover, have confirmed a causal role for acute stress in relapse. The role of chronic stress in relapse vulnerability, however, has received relatively little attention. Therefore, in the present study, we used an abstinence-based relapse model in rats to test the hypothesis that exposure to chronic stress increases subsequent relapse vulnerability. Rats were trained to press a lever for highly palatable food reinforcers in daily 3-h sessions and then tested for food seeking (i.e., responding for food associated cues) both before and after an acute or chronic restraint stress procedure (3h/day×1day or 10days, respectively) or control procedure (unstressed). The second food seeking test was conducted either 1day or 7days after the last restraint. Because chronic stress causes dopamine D1-like receptor-mediated alterations in prefrontal cortex (a relapse node), we also assessed dopaminergic involvement by administering either SCH-23390 (10.0μg/kg; i.p.), a dopamine D1-like receptor antagonist, or vehicle prior to daily treatments. Results showed that chronically, but not acutely, stressed rats displayed increased food seeking 7days, but not 1day, after the last restraint. Importantly, SCH-23390 combined with chronic stress reversed this effect. These results suggest that drugs targeting D 1 -like receptors during chronic stress may help to prevent future relapse in dieters. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Effects of some dopamine antagonists on spatial memory performance in rats--experimental research.

    Science.gov (United States)

    Rusu, Gabriela; Popa, Gratiela; Ochiuz, Lacramioara; Nechifor, M; Tartau, Liliana

    2014-01-01

    Dopamine is a neurotransmitter with an important role in forming long-lasting memories for some time, especially in episodic memory. Literature data show that dopamine receptor stimulation may be detrimental to spatial working memory functions in lab animals. (R)-(+)-7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride derivative--SCH-23390 is a synthetic compound that acts as a selective, high-affinity antagonist of D1 receptors. Experimental studies suggest that SCH 23390 may prevent the spatial working memory disturbances induced by the active substances of marijuana. Melperone is an atypic antipsychotic drug presenting also dopaminergic D2 and 5-HT2A receptor antagonistic activity. This neuroleptic agent is used in the treatment of some types of schizophrenia. Experimental research on the effects of two dopamine receptor antagonists on spatial memory performance in rats. The experiment was carried out in white Wistar rats (200-250g), divided into 3 groups of 7 animals each, treated intraperitoneally with the same volume of solution for 14 days, as follows: Group I (Control): saline solution 0.1 ml/10g kbw; Group II (coded SCH): SCH-23390 0.3 mg/kbw; Group III (coded MLP): melperone 2 mg/kbw. The dopaminergic agent spatial memory performance was assessed by recording spontaneous alternation behavior in a single session in Y-maze. Each animal was placed at the end of one arm and allowed to move freely through the maze during an 8 min session. Alternation was defined as a consecutive entry in three different arms. The alternation percentage was computed with the following formula: number of alternations divided by total number of arm visits minus 2. Data were presented as +/- standard deviation and significance was tested by SPSS Statistics for Windows version 13.0 and ANOVA method. P-values less than 0.05 were considered statistically significant compared to those in the control group. Experimental researches were carried out in

  3. Henoch Schönlein purpura associated with pulmonary adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Tetsuka Takafumi

    2011-06-01

    Full Text Available Abstract Introduction Henoch-Schönlein purpura is a common immunoglobulin A-mediated vasculitis syndrome in children. Henoch-Schönlein purpura can also affect adults and is probably related to malignancy. Case presentation We report the case of a 61-year-old Japanese man who presented for examination after an abnormal shadow was detected by chest radiography. He received a diagnosis of pulmonary adenocarcinoma, stage IV. Purpura on the legs, abdominal pain, diarrhea, hematuria and proteinuria developed at this time. Henoch-Schönlein purpura was diagnosed, base on the clinical symptoms and histological findings of biopsy specimens of the skin, which showed vasculitis with immunoglobulin A deposits. Our patient received chemotherapy with gemcitabine after successful steroid therapy for the Henoch-Schönlein purpura. Conclusion Although hematological malignancies are well-known causes of vasculitides, cases of Henoch-Schönlein purpura associated with lung adenocarcinoma are rare. Our patient was treated with corticosteroid therapy, which cleared the purpura and cytotoxic chemotherapy for the non-small cell lung cancer. However, he died from heart failure due to cardiac tamponade.

  4. Link between D sub 1 and D sub 2 dopamine receptors is reduced in schizophrenia and Huntington diseased brain

    Energy Technology Data Exchange (ETDEWEB)

    Seeman, P.; Niznik, H.B.; Guan, H.C.; Booth, G.; Ulpian, C. (Univ. of Toronto (Canada))

    1989-12-01

    Dopamine receptor types D{sub 1} and D{sub 2} can oppose enhance each other's actions for electrical, biochemical, and psychomotor effects. The authors report a D{sub 1}-D{sub 2} interaction in homogenized tissue as revealed by ligand binding. D{sub 2} agonists lowered the binding of ({sup 3}H)raclopride to D{sub 2} receptors in striatal and anterior pituitary tissues. Pretreating the tissue with the D{sub 1}-selective antagonist SCH 23390 prevented the agonist-induced decrease in ({sup 3}H)raclopride binding to D{sub 2} sites in the striatum but not in the anterior pituitary, which has no D{sub 1} receptors. Conversely, a dopamine-induced reduction in the binding of ({sup 3}H)SCH 23390 to D{sub 1} receptors could be prevented by the D{sub 2}-selective antagonist eticlopride. Receptor photolabeling experiments confirmed both these D{sub 1}-D{sub 2} interactions. The blocking effect by SCH 23390 was similar to that produced by a nonhydrolyzable guanine nucleotide analogue, and SCH 23390 reduced the number of agonist-labeled D{sub 2} receptors in the high-affinity state. Thus, the D{sub 1}-D{sub 2} link may be mediated by guanine nucleotide-binding protein components. The link may underlie D{sub 1}-D{sub 2} interactions influencing behavior, since the link was missing in over half the postmortem striata from patients with schizophrenia and Huntington disease (both diseases that show some hyperdopamine signs) but was present in human control, Alzheimer, and Parkinson striata.

  5. Differential involvement of dopamine D-1 and D-2 receptors in the circling behaviour induced by apomorphine, SK & F 38393, pergolide and LY 171555 in 6-hydroxydopamine-lesioned rats.

    Science.gov (United States)

    Arnt, J; Hyttel, J

    1985-01-01

    The antagonistic effect of dopamine (DA) D-1 and D-2 antagonists against circling behaviour induced by various DA agonists in 6-OHDA-lesioned rats has been investigated. DA D-1/D-2 selectivity of agonists in vitro was measured by the stimulatory effect on DA-sensitive adenylate cyclase in rat striatal homogenates (D-1), the inhibitory effect on electrically-induced release of 3H-DA in rabbit striatal slices (D-2) and the affinity to 3H-piflutixol (D-1) and 3H-spiroperidol (D-2) binding sites in rat striatal membranes. The contralateral circling behaviour induced by the DA D-1 agonist SK & F 38393 was blocked by the DA D-1 antagonist, SCH 23390, and by the mixed DA D-1/D-2 antagonist cis(Z)-flupentixol, but was not influenced by the DA D-2 antagonists spiroperidol and clebopride. In contrast, circling behaviour induced by the preferential DA D-2 agonists pergolide and LY 171555 was blocked by clebopride, spiroperidol, and cis(Z)-flupentixol, but weakly or not influenced by SCH 23390. Apomorphine-induced circling behaviour was blocked by cis(Z)-flupentixol, partially antagonized by SCH 23390 and clebopride but not inhibited by spiroperidol, although the time-course of circling was changed. Combinations of SCH 23390 with spiroperidol or clebopride in low doses completely blocked the effect of apomorphine. These results indicate that DA D-1 and D-2 receptors mediate circling behaviour through separate mechanisms which can be independently manipulated with respective agonists and antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Effects of dopamine D1 receptor blockade in the prelimbic prefrontal cortex or lateral dorsal striatum on frontostriatal function in Wistar and Spontaneously Hypertensive Rats.

    Science.gov (United States)

    Gauthier, Jamie M; Tassin, David H; Dwoskin, Linda P; Kantak, Kathleen M

    2014-07-15

    Attention Deficit Hyperactivity Disorder (ADHD) is associated with dysfunctional prefrontal and striatal circuitry and dysregulated dopamine neurotransmission. Spontaneously Hypertensive Rats (SHR), a heuristically useful animal model of ADHD, were evaluated against normotensive Wistar (WIS) controls to determine whether dopamine D1 receptor blockade of either prelimbic prefrontal cortex (plPFC) or lateral dorsal striatum (lDST) altered learning functions of both interconnected sites. A strategy set shifting task measured plPFC function (behavioral flexibility/executive function) and a reward devaluation task measured lDST function (habitual responding). Prior to tests, rats received bilateral infusions of SCH 23390 (1.0 μg/side) or vehicle into plPFC or lDST. Following vehicle, SHR exhibited longer lever press reaction times, more trial omissions, and fewer completed trials during the set shift test compared to WIS, indicating slower decision-making and attentional/motivational impairment in SHR. After reward devaluation, vehicle-treated SHR responded less than WIS, indicating relatively less habitual responding in SHR. After SCH 23390 infusions into plPFC, WIS expressed the same behavioral phenotype as vehicle-treated SHR during set shift and reward devaluation tests. In SHR, SCH 23390 infusions into plPFC exacerbated behavioral deficits in the set shift test and maintained the lower rate of responding in the reward devaluation test. SCH 23390 infusions into lDST did not modify set shifting in either strain, but produced lower rates of responding than vehicle infusions after reward devaluation in WIS. This research provides pharmacological evidence for unidirectional interactions between prefrontal and striatal brain regions, which has implications for the neurological basis of ADHD and its treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Henoch-Schönlein Purpura

    DEFF Research Database (Denmark)

    Hetland, Liv Eline; Susrud, Kjærsti Sørensen; Lindahl, Kim Hein

    2017-01-01

    Henoch-Schönlein purpura is the most common childhood vasculitis, but may also affect adults. This article reviews the literature since 2011 on advances in diagnosis, clinical disease manifestations, pathophysiology and treatment of Henoch-Schönlein purpura. The clinical manifestations are thought...... studies are needed to confirm these findings. Cancer screening should be considered in older males diagnosed with Henoch-Schönlein purpura....

  8. Mitochondrial genomic dysfunction causes dephosphorylation of Sch9 in the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Kawai, Shigeyuki; Urban, Jörg; Piccolis, Manuele; Panchaud, Nicolas; De Virgilio, Claudio; Loewith, Robbie

    2011-10-01

    TORC1-dependent phosphorylation of Saccharomyces cerevisiae Sch9 was dramatically reduced upon exposure to a protonophore or in respiration-incompetent ρ(0) cells but not in respiration-incompetent pet mutants, providing important insight into the molecular mechanisms governing interorganellar signaling in general and retrograde signaling in particular.

  9. Differential regulation of dopamine receptors after chronic typical and atypical antipsychotic drug treatment

    International Nuclear Information System (INIS)

    Creese, I.; Florijn, W.J.; Tarazi, F.I.

    1997-01-01

    Changes in dopamine receptor subtype binding in different brain regions were examined after 28 days treatment of rats with haloperidol, raclopride, clozapine or SCH23390 using in vitro receptor autoradiography. [ 3 H]7-hydroxy-N,N-di-n-propyl-2-aminotetralin binding to dopamine D 3 receptors was not changed in any brain region by any of the drug treatments. [ 3 H]SCH23390 was only increased by chronic SCH23390 treatment. Haloperidol significantly increased [ 3 H]nemonapride and [ 3 H]spiperone binding to dopamine D 2 -like receptors in the caudate-putamen. In contrast, haloperidol caused a small, significant increase in [ 3 H]raclopride binding in the lateral caudate-putamen only. Raclopride also elevated, but to a lesser extent [ 3 H]nemonapride and [ 3 H]spiperone binding in caudate-putamen, whereas it did not affect [ 3 H]raclopride binding. Clozapine did not significantly change D 2 -like striatal binding of [ 3 H]nemonapride, [ 3 H]spiperone or [ 3 H]raclopride. The differences in radioligand binding suggest that [ 3 H]nemonapride and [ 3 H]spiperone may be binding to additional subsets of dopamine D 2 -like receptors (including D 4 -like receptors) that are not recognized by [ 3 H]raclopride, which has high affinity for D 2 and D 3 receptors only.Quantification of [ 3 H]nemonapride or [ 3 H]spiperone binding in the presence of 300 nM raclopride (to block D 2 and D 3 receptors) revealed that haloperidol, raclopride and clozapine up-regulated D 4 -like receptors in the caudate-putamen using either radioligand. These results suggest that D 4 -like receptors may be a common site of action of both typical and atypical antipsychotics. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  10. High-dose methylprednisolone pulse therapy for treatment of refractory intestinal involvement caused by Henoch-Schönlein purpura: a case report.

    Science.gov (United States)

    Kang, Hyun Sik; Chung, Hee Sup; Kang, Ki-Soo; Han, Kyoung Hee

    2015-03-24

    Henoch-Schönlein purpura is an immunoglobulin A-mediated, small vascular inflammatory disease that can be associated with palpable purpura, arthralgia, abdominal pain, or nephritis. The presence of purpura facilitates the diagnosis of Henoch-Schönlein purpura at the onset of associated symptoms, whereas the absence of purpura makes the diagnosis challenging. It is important to diagnose Henoch-Schönlein purpura with delayed-onset skin purpura to avoid unnecessary surgery for acute abdomen. Most cases of Henoch-Schönlein purpura with severe abdominal pain are treated with low-dose steroids and intravenous immunoglobulin. A 15-year-old Korean girl complained of severe abdominal pain and delayed-onset purpura on admission. Henoch-Schönlein purpura was diagnosed based on endoscopic findings of hemorrhagic duodenitis and duodenal vasculitis and abdominal computed tomography findings of edematous bowels. Two common initial treatments, a low-dose steroid and intravenous immunoglobulin, were administered, but there was no improvement for 1 month. Subsequently, we used high-dose intravenous methylprednisolone pulse therapy (30 mg/kg/day, with a maximum of 1g/day), which dramatically alleviated her abdominal symptoms. High-dose intravenous methylprednisolone pulse therapy can be used as the ultimate treatment for delayed-onset Henoch-Schönlein purpura with severe abdominal pain when symptoms do not improve after low-dose steroid and intravenous immunoglobulin treatments.

  11. Experimental Evolution Reveals Interplay between Sch9 and Polyploid Stability in Yeast.

    Directory of Open Access Journals (Sweden)

    Yi-Jin Lu

    2016-11-01

    Full Text Available Polyploidization has crucial impacts on the evolution of different eukaryotic lineages including fungi, plants and animals. Recent genome data suggest that, for many polyploidization events, all duplicated chromosomes are maintained and genome reorganizations occur much later during evolution. However, newly-formed polyploid genomes are intrinsically unstable and often quickly degenerate into aneuploidy or diploidy. The transition between these two states remains enigmatic. In this study, laboratory evolution experiments were conducted to investigate this phenomenon. We show that robust tetraploidy is achieved in evolved yeast cells by increasing the abundance of Sch9-a protein kinase activated by the TORC1 (Target of Rapamycin Complex 1 and other signaling pathways. Overexpressing SCH9, but not TOR1, allows newly-formed tetraploids to exhibit evolved phenotypes and knocking out SCH9 diminishes the evolved phenotypes. Furthermore, when cells were challenged with conditions causing ancestral cells to evolve aneuploidy, tetraploidy was maintained in the evolved lines. Our results reveal a determinant role for Sch9 during the early stage of polyploid evolution.

  12. Importance of D1 and D2 receptor stimulation for the induction and expression of cocaine-induced behavioral sensitization in preweanling rats.

    Science.gov (United States)

    McDougall, Sanders A; Rudberg, Krista N; Veliz, Ana; Dhargalkar, Janhavi M; Garcia, Aleesha S; Romero, Loveth C; Gonzalez, Ashley E; Mohd-Yusof, Alena; Crawford, Cynthia A

    2017-05-30

    The behavioral manifestations of psychostimulant-induced sensitization vary markedly between young and adult rats, suggesting that the neural mechanisms mediating this phenomenon differ across ontogeny. In this project we examined the importance of D1 and D2 receptors for the induction and expression of cocaine-induced behavioral sensitization during the preweanling period. In the behavioral experiments, rats were injected with reversible D1 and/or D2 antagonists (SCH23390 and/or raclopride) or an irreversible receptor antagonist (EEDQ) either before cocaine administration on the pretreatment day (induction) or before cocaine challenge on the test day (expression). In the EEDQ experiments, receptor specificity was assessed by using selective dopamine antagonists to protect D1 and/or D2 receptors from inactivation. Receptor binding assays showed that EEDQ caused substantial reductions in dorsal striatal D1 and D2 binding sites, while SCH23390 and raclopride fully protected D1 and D2 receptors from EEDQ-induced alkylation. Behavioral results showed that neither D1 nor D2 receptor stimulation was necessary for the induction of cocaine sensitization in preweanling rats. EEDQ disrupted the sensitization process, suggesting that another receptor type sensitive to EEDQ alkylation was necessary for the induction process. Expression of the sensitized response was prevented by an acute injection of a D1 receptor antagonist. The pattern of DA antagonist-induced effects described for preweanling rats is, with few exceptions, similar to what is observed when the same drugs are administered to adult rats. Thus, it appears that maturational changes in D1 and D2 receptor systems are not responsible for ontogenetic differences in the behavioral manifestation of cocaine sensitization. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Homicide by Sch from a syringe-like dart ejected by a compound crossbow.

    Science.gov (United States)

    Guo, Wei; Luo, Guochang; Wang, Hao; Meng, Xiangzhi

    2015-02-01

    The compound crossbow can be used to eject syringe-like dart loaded with poisonous solution. Succinylcholine (Sch) is a short-acting neuromuscular blocker medically used to achieve complete relaxation of muscle for a good intubation condition. Without the help of an artificial respirator, intramuscular injection of a large dose of Sch can paralyze the respiratory muscle and result in the receiver's death. In this paper, we present the homicide case of a young male killed by Sch from a syringe-like dart ejected by a compound crossbow. The subcutaneous and muscular hemorrhages observed around the entry were more severe than that caused by a medical injection. Additionally, other autopsy results showed the external appearance of a pinhole, general asphyxia signs and pathological findings which were not characteristic. The discovery of a syringe-like dart at the scene is the critical clue and reason for analyzing for Sch, which is commonly used to load syringe-like dart to paralyze and steal dog in the countryside of China. Copyright © 2014 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  14. Effects of dopamine D1-like and D2-like antagonists on cocaine discrimination in muscarinic receptor knockout mice.

    Science.gov (United States)

    Thomsen, Morgane; Caine, Simon Barak

    2016-04-05

    Muscarinic and dopamine brain systems interact intimately, and muscarinic receptor ligands, like dopamine ligands, can modulate the reinforcing and discriminative stimulus (S(D)) effects of cocaine. To enlighten the dopamine/muscarinic interactions as they pertain to the S(D) effects of cocaine, we evaluated whether muscarinic M1, M2 or M4 receptors are necessary for dopamine D1 and/or D2 antagonist mediated modulation of the S(D) effects of cocaine. Knockout mice lacking M1, M2, or M4 receptors, as well as control wild-type mice and outbred Swiss-Webster mice, were trained to discriminate 10mg/kg cocaine from saline in a food-reinforced drug discrimination procedure. Effects of pretreatments with the dopamine D1 antagonist SCH 23390 and the dopamine D2 antagonist eticlopride were evaluated. In intact mice, both SCH 23390 and eticlopride attenuated the cocaine discriminative stimulus effect, as expected. SCH 23390 similarly attenuated the cocaine discriminative stimulus effect in M1 knockout mice, but not in mice lacking M2 or M4 receptors. The effects of eticlopride were comparable in each knockout strain. These findings demonstrate differences in the way that D1 and D2 antagonists modulate the S(D) effects of cocaine, D1 modulation being at least partially dependent upon activity at the inhibitory M2/M4 muscarinic subtypes, while D2 modulation appeared independent of these systems. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Dopamine D1 receptors are responsible for stress-induced emotional memory deficit in mice.

    Science.gov (United States)

    Wang, Yongfu; Wu, Jing; Zhu, Bi; Li, Chaocui; Cai, Jing-Xia

    2012-03-01

    It is established that stress impairs spatial learning and memory via the hypothalamus-pituitary-adrenal axis response. Dopamine D1 receptors were also shown to be responsible for a stress-induced deficit of working memory. However, whether stress affects the subsequent emotional learning and memory is not elucidated yet. Here, we employed the well-established one-trial step-through task to study the effect of an acute psychological stress (induced by tail hanging for 5, 10, or 20 min) on emotional learning and memory, and the possible mechanisms as well. We demonstrated that tail hanging induced an obvious stress response. Either an acute tail-hanging stress or a single dose of intraperitoneally injected dopamine D1 receptor antagonist (SCH23390) significantly decreased the step-through latency in the one-trial step-through task. However, SCH23390 prevented the acute tail-hanging stress-induced decrease in the step-through latency. In addition, the effects of tail-hanging stress and/or SCH23390 on the changes in step-through latency were not through non-memory factors such as nociceptive perception and motor function. Our data indicate that the hyperactivation of dopamine D1 receptors mediated the stress-induced deficit of emotional learning and memory. This study may have clinical significance given that psychological stress is considered to play a role in susceptibility to some mental diseases such as depression and post-traumatic stress disorder.

  16. Impairments of exploration and memory after systemic or prelimbic D1-receptor antagonism in rats

    DEFF Research Database (Denmark)

    Clausen, Bettina; Schachtman, Todd R.; Mark, Louise T.

    2011-01-01

    to examine the effects on memory: cross-maze and object recognition task. Systemic administration reduced spatial exploration in cross-maze as well as in an open field test, and also reduced object exploration. Spatial (hippocampus-dependent) short-term memory was inhibited in the cross-maze and non......-spatial short-term object retention was also impaired. In contrast to these systemic effects, bilateral injections of SCH23390 into the prelimbic cortices altered neither spatial nor object exploration, but did inhibit short-term memory in both cross-maze and object recognition task. Therefore, the inhibiting......D1-receptor antagonism is known to impair rodent memory but also inhibits spontaneous exploration of stimuli to be remembered. Hypo-exploration could contribute to impaired memory by influencing event processing. In order to explore this effect, the D1 receptor antagonist, SCH23390...

  17. Levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain in conscious rats

    Directory of Open Access Journals (Sweden)

    Toshikatsu Okumura

    2016-02-01

    Subcutaneously (80 mg/rat or intracisternally (2.5 μg/rat administered levodopa significantly increased the threshold of colonic distension-induced AWR in conscious rats. The dose difference to induce the antinociceptive action suggests levodopa acts centrally to exert its antinociceptive action against colonic distension. While neither sulpiride, a D2 dopamine receptor antagonist, nor SCH23390, a D1 dopamine receptor antagonist by itself changed the threshold of colonic distension-induced AWR, the intracisternally injected levodopa-induced antinociceptive action was significantly blocked by pretreatment with subcutaneously administered sulpiride but not SCH23390. Treatment with intracisternal SB334867, an orexin 1 receptor antagonist, significantly blocked the subcutaneously administered levodopa-induced antinociceptive action. These results suggest that levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain.

  18. Pharmacological differences between memory consolidation of habituation to an open field and inhibitory avoidance learning

    Directory of Open Access Journals (Sweden)

    Vianna M.R.M.

    2001-01-01

    Full Text Available Rats implanted bilaterally with cannulae in the CA1 region of the dorsal hippocampus or the entorhinal cortex were submitted to either a one-trial inhibitory avoidance task, or to 5 min of habituation to an open field. Immediately after training, they received intrahippocampal or intraentorhinal 0.5-µl infusions of saline, of a vehicle (2% dimethylsulfoxide in saline, of the glutamatergic N-methyl-D-aspartate (NMDA receptor antagonist 2-amino-5-phosphono pentanoic acid (AP5, of the protein kinase A inhibitor Rp-cAMPs (0.5 µg/side, of the calcium-calmodulin protein kinase II inhibitor KN-62, of the dopaminergic D1 antagonist SCH23390, or of the mitogen-activated protein kinase kinase inhibitor PD098059. Animals were tested in each task 24 h after training. Intrahippocampal KN-62 was amnestic for habituation; none of the other treatments had any effect on the retention of this task. In contrast, all of them strongly affected memory of the avoidance task. Intrahippocampal Rp-cAMPs, KN-62 and AP5, and intraentorhinal Rp-cAMPs, KN-62, PD098059 and SCH23390 caused retrograde amnesia. In view of the known actions of the treatments used, the present findings point to important biochemical differences in memory consolidation processes of the two tasks.

  19. The new Federal Act for the protection against nuisances (BImSchV)

    International Nuclear Information System (INIS)

    Froeba, K.; Thomas, L.

    1977-01-01

    Text of the decree with introduction and comprehensive explanations. Furnaces (1st decree of BImSchV); Chemical purification installations (2nd decree of BImSchV); sulfur content of light fuel oil and diesel oil (3rd decree of BImSchV); installations subject to licensing (4th decree of BImSchV); persons authorized with the protection against nuisances (5th decree of BImSchV); know-how and reliability of these persons (6th decree of BImSchV); ejection limitation for wood dust (7th decree of BImSchV); limitation of noise made by lawn mowing machines (8th decree of BImSchV); principles of the licensing procedure (9th decree of BImSchV). Text of the Federal Act for the Protection Against Nuisances. (orig.) [de

  20. Arnold Schőnberg - analiza Klavirske suite opus 25

    OpenAIRE

    Voler, Saša

    2018-01-01

    Magistrsko delo vsebuje oris življenja Arnolda Schönberga in njegovega glasbenega opusa. Arnolda Schönberga spoznamo kot učenca in kot učitelja, spoznamo ga kot abstraktnega človeka, ki se bojuje s triskaidekafobijo, ki ima velik vpliv na njegova dela. V magistrskem delu je tudi razlaga Schönbergovih odnosov s skladatelji njegovega kroga, ki so nanj tako ali drugače vplivali, hkrati pa spoznamo, da se je Schönberg posvečal tudi slikarstvu. V začetnem opisu glasbe 20.stoletja spoznamo obdobje,...

  1. Differential regulation of dopamine receptors after chronic typical and atypical antipsychotic drug treatment

    Energy Technology Data Exchange (ETDEWEB)

    Creese, I; Florijn, W J; Tarazi, F I [Center for Molecular and Behavioral Neuroscience, Rutgers University, 197 University Avenue, Newark, NJ (United States)

    1997-04-14

    Changes in dopamine receptor subtype binding in different brain regions were examined after 28 days treatment of rats with haloperidol, raclopride, clozapine or SCH23390 using in vitro receptor autoradiography. [{sup 3}H]7-hydroxy-N,N-di-n-propyl-2-aminotetralin binding to dopamine D{sub 3} receptors was not changed in any brain region by any of the drug treatments. [{sup 3}H]SCH23390 was only increased by chronic SCH23390 treatment. Haloperidol significantly increased [{sup 3}H]nemonapride and [{sup 3}H]spiperone binding to dopamine D{sub 2}-like receptors in the caudate-putamen. In contrast, haloperidol caused a small, significant increase in [{sup 3}H]raclopride binding in the lateral caudate-putamen only. Raclopride also elevated, but to a lesser extent [{sup 3}H]nemonapride and [{sup 3}H]spiperone binding in caudate-putamen, whereas it did not affect [{sup 3}H]raclopride binding. Clozapine did not significantly change D{sub 2}-like striatal binding of [{sup 3}H]nemonapride, [{sup 3}H]spiperone or [{sup 3}H]raclopride. The differences in radioligand binding suggest that [{sup 3}H]nemonapride and [{sup 3}H]spiperone may be binding to additional subsets of dopamine D{sub 2}-like receptors (including D{sub 4}-like receptors) that are not recognized by [{sup 3}H]raclopride, which has high affinity for D{sub 2} and D{sub 3} receptors only.Quantification of [{sup 3}H]nemonapride or [{sup 3}H]spiperone binding in the presence of 300 nM raclopride (to block D{sub 2} and D{sub 3} receptors) revealed that haloperidol, raclopride and clozapine up-regulated D{sub 4}-like receptors in the caudate-putamen using either radioligand. These results suggest that D{sub 4}-like receptors may be a common site of action of both typical and atypical antipsychotics. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  2. The pathophysiological functions mediated by D-1 dopamine receptors

    International Nuclear Information System (INIS)

    Goldstein, M.; Kuga, S.; Meller, E.; SHimizu, Y.

    1986-01-01

    This chapter describes some behavioral responses which might be mediated by D 1 and D 2 DA receptors, and the authors discuss their clinical relevance. It was of considerable interest to determine whether a selective D 1 DA antagonist, such as SCH 23390, will induce catalepsy and whether this behavior is mediated by D 1 , or by both D 1 and D 2 DA receptors. Rats were used in the experiments. The authors examined whether the addition of the S 2 antagonist ketanserin affects the displacement of 3 H-Spi by SCH 23390. Induction of self-mutilating biting (SMB) behavior in monkeys with unilateral ventromedial tegmental (VMT) lesions by DA agonists and its prevention by DA antagonists is examined. The authors also discuss the possible relationships between abnormal guanine nucleotide metabolism and dopaminergic neuronal function through the implications in LeschNyhan syndrome and in some mental disorders

  3. A critical role of nucleus accumbens dopamine D1-family receptors in renewal of alcohol seeking after punishment-imposed abstinence.

    Science.gov (United States)

    Marchant, Nathan J; Kaganovsky, Konstantin

    2015-06-01

    In humans, places or contexts previously associated with alcohol use often provoke relapse during abstinence. This phenomenon is modeled in laboratory animals using the ABA renewal procedure, in which extinction training in context (B) suppresses alcohol seeking, and renewal of this seeking occurs when the animal returns to the original training context (A). However, extinction training does not adequately capture the motivation for abstinence in human alcoholics who typically self-initiate abstinence in response to the negative consequences of excessive use. We recently developed a procedure to study renewal in laboratory rats after abstinence imposed by negative consequences (footshock punishment). The mechanisms of renewal of punished alcohol seeking are largely unknown. Here, we used the D1-family receptor antagonist SCH 23390 to examine the role of nucleus accumbens (NAc) shell and core dopamine in renewal of alcohol seeking after punishment-imposed abstinence. We trained alcohol-preferring "P rats" to self-administer 20% alcohol in Context A and subsequently suppressed alcohol taking via response-contingent footshock punishment in Context B. We tested the effects of systemic, NAc shell, or NAc core injections of SCH 23390 on renewal of alcohol seeking after punishment-imposed abstinence. We found that both systemic and NAc shell and core injections of SCH 23390 decreased renewal of punished alcohol seeking. Our results demonstrate a critical role of NAc dopamine in renewal of alcohol seeking after punishment-imposed abstinence. We discuss these results in reference to the brain mechanisms of renewal of alcohol seeking after extinction versus punishment. (c) 2015 APA, all rights reserved).

  4. Blockade of dopamine D1-family receptors attenuates the mania-like hyperactive, risk-preferring, and high motivation behavioral profile of mice with low dopamine transporter levels.

    Science.gov (United States)

    Milienne-Petiot, Morgane; Groenink, Lucianne; Minassian, Arpi; Young, Jared W

    2017-10-01

    Patients with bipolar disorder mania exhibit poor cognition, impulsivity, risk-taking, and goal-directed activity that negatively impact their quality of life. To date, existing treatments for bipolar disorder do not adequately remediate cognitive dysfunction. Reducing dopamine transporter expression recreates many bipolar disorder mania-relevant behaviors (i.e. hyperactivity and risk-taking). The current study investigated whether dopamine D 1 -family receptor blockade would attenuate the risk-taking, hypermotivation, and hyperactivity of dopamine transporter knockdown mice. Dopamine transporter knockdown and wild-type littermate mice were tested in mouse versions of the Iowa Gambling Task (risk-taking), Progressive Ratio Breakpoint Test (effortful motivation), and Behavioral Pattern Monitor (activity). Prior to testing, the mice were treated with the dopamine D 1 -family receptor antagonist SCH 23390 hydrochloride (0.03, 0.1, or 0.3 mg/kg), or vehicle. Dopamine transporter knockdown mice exhibited hyperactivity and hyperexploration, hypermotivation, and risk-taking preference compared with wild-type littermates. SCH 23390 hydrochloride treatment decreased premature responding in dopamine transporter knockdown mice and attenuated their hypermotivation. SCH 23390 hydrochloride flattened the safe/risk preference, while reducing activity and exploratory levels of both genotypes similarly. Dopamine transporter knockdown mice exhibited mania-relevant behavior compared to wild-type mice. Systemic dopamine D 1 -family receptor antagonism attenuated these behaviors in dopamine transporter knockdown, but not all effects were specific to only the knockdown mice. The normalization of behavior via blockade of dopamine D 1 -family receptors supports the hypothesis that D 1 and/or D 5 receptors could contribute to the mania-relevant behaviors of dopamine transporter knockdown mice.

  5. Cross-talk between an activator of nuclear receptors-mediated transcription and the D1 dopamine receptor signaling pathway.

    Science.gov (United States)

    Schmidt, Azriel; Vogel, Robert; Rutledge, Su Jane; Opas, Evan E; Rodan, Gideon A; Friedman, Eitan

    2005-03-01

    Nuclear receptors are transcription factors that usually interact, in a ligand-dependent manner, with specific DNA sequences located within promoters of target genes. The nuclear receptors can also be controlled in a ligand-independent manner via the action of membrane receptors and cellular signaling pathways. 5-Tetradecyloxy-2-furancarboxylic acid (TOFA) was shown to stimulate transcription from the MMTV promoter via chimeric receptors that consist of the DNA binding domain of GR and the ligand binding regions of the PPARbeta or LXRbeta nuclear receptors (GR/PPARbeta and GR/LXRbeta). TOFA and hydroxycholesterols also modulate transcription from NF-kappaB- and AP-1-controlled reporter genes and induce neurite differentiation in PC12 cells. In CV-1 cells that express D(1) dopamine receptors, D(1) dopamine receptor stimulation was found to inhibit TOFA-stimulated transcription from the MMTV promoter that is under the control of chimeric GR/PPARbeta and GR/LXRbeta receptors. Treatment with the D(1) dopamine receptor antagonist, SCH23390, prevented dopamine-mediated suppression of transcription, and by itself increased transcription controlled by GR/LXRbeta. Furthermore, combined treatment of CV-1 cells with TOFA and SCH23390 increased transcription controlled by the GR/LXRbeta chimeric receptor synergistically. The significance of this in vitro synergy was demonstrated in vivo, by the observation that SCH23390 (but not haloperidol)-mediated catalepsy in rats was potentiated by TOFA, thus showing that an agent that mimics the in vitro activities of compounds that activate members of the LXR and PPAR receptor families can influence D1 dopamine receptor elicited responses.

  6. Roles of NMDA and dopamine D1 and D2 receptors in the acquisition and expression of flavor preferences conditioned by oral glucose in rats.

    Science.gov (United States)

    Dela Cruz, J A D; Coke, T; Icaza-Cukali, D; Khalifa, N; Bodnar, R J

    2014-10-01

    Animals learn to prefer flavors associated with the intake of sugar (sucrose, fructose, glucose) and fat (corn oil: CO) solutions. Conditioned flavor preferences (CFP) have been elicited for sugars based on orosensory (flavor-flavor: e.g., fructose-CFP) and post-ingestive (flavor-nutrient: e.g., intragastric (IG) glucose-CFP) processes. Dopamine (DA) D1, DA D2 and NMDA receptor antagonism differentially eliminate the acquisition and expression of fructose-CFP and IG glucose-CFP. However, pharmacological analysis of fat (CO)-CFP, mediated by both flavor-flavor and flavor-nutrient processes, indicated that acquisition and expression of fat-CFP were minimally affected by systemic DA D1 and D2 antagonists, and were reduced by NMDA antagonism. Therefore, the present study examined whether systemic DA D1 (SCH23390), DA D2 (raclopride) or NMDA (MK-801) receptor antagonists altered acquisition and/or expression of CFP induced by oral glucose that should be mediated by both flavor-flavor and flavor-nutrient processes. Oral glucose-CFP was elicited following by training rats to drink one novel flavor (CS+, e.g., cherry) mixed in 8% glucose and another flavor (CS-, e.g., grape) mixed in 2% glucose. In expression studies, food-restricted rats drank these solutions in one-bottle sessions (2 h) over 10 days. Subsequent two-bottle tests with the CS+ and CS- flavors mixed in 2% glucose occurred 0.5 h after systemic administration of vehicle (VEH), SCH23390 (50-800 nmol/kg), raclopride (50-800 nmol/kg) or MK-801 (50-200 μg/kg). Rats displayed a robust CS+ preference following VEH treatment (94-95%) which was significantly though marginally attenuated by SCH23390 (67-70%), raclopride (77%) or MK-801 (70%) at doses that also markedly reduced overall CS intake. In separate acquisition studies, rats received VEH, SCH23390 (50-400 nmol/kg), raclopride (50-400 nmol/kg) or MK-801 (100 μg/kg) 0.5 h prior to ten 1-bottle training trials with CS+/8%G and CS-/2%G training solutions that was

  7. Posaconazole (Noxafil, SCH 56592), a new azole antifungal drug, was a discovery based on the isolation and mass spectral characterization of a circulating metabolite of an earlier lead (SCH 51048).

    Science.gov (United States)

    Nomeir, Amin A; Pramanik, Birendra N; Heimark, Larry; Bennett, Frank; Veals, John; Bartner, Peter; Hilbert, Maryjane; Saksena, Anil; McNamara, Paul; Girijavallabhan, Viyyoor; Ganguly, Ashit K; Lovey, Raymond; Pike, Russell; Wang, Haiyan; Liu, Yi-Tsung; Kumari, Pramila; Korfmacher, Walter; Lin, Chin-Chung; Cacciapuoti, Anthony; Loebenberg, David; Hare, Roberta; Miller, George; Pickett, Cecil

    2008-04-01

    Posaconazole (SCH 56592) is a novel triazole antifungal drug that is marketed in Europe and the United States under the trade name 'Noxafil' for prophylaxis against invasive fungal infections. SCH 56592 was discovered as a possible active metabolite of SCH 51048, an earlier lead. Initial studies have shown that serum concentrations determined by a microbiological assay were higher than those determined by HPLC from animals dosed with SCH 51048. Subsequently, several animals species were dosed with (3)H-SCH 51048 and the serum was analyzed for total radioactivity, SCH 51048 concentration and antifungal activity. The antifungal activity was higher than that expected based on SCH 51048 serum concentrations, confirming the presence of active metabolite(s). Metabolite profiling of serum samples at selected time intervals pinpointed the peak that was suspected to be the active metabolite. Consequently, (3)H-SCH 51048 was administered to a large group of mice, the serum was harvested and the metabolite was isolated by extraction and semipreparative HPLC. LC-MS/MS analysis suggested that the active metabolite is a secondary alcohol with the hydroxyl group in the aliphatic side chain of SCH 51048. All corresponding monohydroxylated diastereomeric mixtures were synthesized and characterized. The HPLC retention time and LC-MS/MS spectra of the diastereomeric secondary alcohols of SCH 51048 were similar to those of the isolated active metabolite. Finally, all corresponding individual monohydroxylated diasteriomers were synthesized and evaluated for in vitro and in vivo antifungal potencies, as well as pharmacokinetics. SCH 56592 emerged as the candidate with the best overall profile.

  8. Reflections on the Schön affair

    Science.gov (United States)

    Brandon, David; Santic, Branko

    2009-07-01

    In her feature article on the fraud perpetrated by Jan Hendrik Schön (May pp24-29), Eugenie Samuel Reich concludes that the fake data Schön generated at Bell Labs were designed primarily to meet the expectations of his peers. She is probably right, but the Schön case was by no means the first of its kind. A century ago the Piltdown fraud, in which medieval cranial fragments were matched with part of an orang-utan jaw bone, convinced British archaeologists and palaeontologists that early hominids developed on the South Downs. The scientific evidence was never fully accepted outside the British Empire, but it still took the UK's Natural History Museum 50 years to recognize the hoax. "Piltdown man" was created to meet the expectations of the British archaeological community, and hence the fraud succeeded.

  9. Contribution of a mesocorticolimbic subcircuit to drug context-induced reinstatement of cocaine-seeking behavior in rats.

    Science.gov (United States)

    Lasseter, Heather C; Xie, Xiaohu; Arguello, Amy A; Wells, Audrey M; Hodges, Matthew A; Fuchs, Rita A

    2014-02-01

    Cocaine-seeking behavior triggered by drug-paired environmental context exposure is dependent on orbitofrontal cortex (OFC)-basolateral amygdala (BLA) interactions. Here, we present evidence supporting the hypothesis that dopaminergic input from the ventral tegmental area (VTA) to the OFC critically regulates these interactions. In experiment 1, we employed site-specific pharmacological manipulations to show that dopamine D1-like receptor stimulation in the OFC is required for drug context-induced reinstatement of cocaine-seeking behavior following extinction training in an alternate context. Intra-OFC pretreatment with the dopamine D1-like receptor antagonist, SCH23390, dose-dependently attenuated cocaine-seeking behavior in an anatomically selective manner, without altering motor performance. Furthermore, the effects of SCH23390 could be surmounted by co-administration of a sub-threshold dose of the D1-like receptor agonist, SKF81297. In experiment 2, we examined effects of D1-like receptor antagonism in the OFC on OFC-BLA interactions using a functional disconnection manipulation. Unilateral SCH23390 administration into the OFC plus GABA agonist-induced neural inactivation of the contralateral or ipsilateral BLA disrupted drug context-induced cocaine-seeking behavior relative to vehicle, while independent unilateral manipulations of these brain regions were without effect. Finally, in experiment 3, we used fluorescent retrograde tracers to demonstrate that the VTA, but not the substantia nigra, sends dense intra- and interhemispheric projections to the OFC, which in turn has reciprocal bi-hemispheric connections with the BLA. These findings support that dopaminergic input from the VTA, via dopamine D1-like receptor stimulation in the OFC, is required for OFC-BLA functional interactions. Thus, a VTA-OFC-BLA neural circuit promotes drug context-induced motivated behavior.

  10. SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infection in vitro and in vivo.

    Science.gov (United States)

    Strizki, J M; Xu, S; Wagner, N E; Wojcik, L; Liu, J; Hou, Y; Endres, M; Palani, A; Shapiro, S; Clader, J W; Greenlee, W J; Tagat, J R; McCombie, S; Cox, K; Fawzi, A B; Chou, C C; Pugliese-Sivo, C; Davies, L; Moreno, M E; Ho, D D; Trkola, A; Stoddart, C A; Moore, J P; Reyes, G R; Baroudy, B M

    2001-10-23

    We describe here the identification and properties of SCH-C (SCH 351125), a small molecule inhibitor of HIV-1 entry via the CCR5 coreceptor. SCH-C, an oxime-piperidine compound, is a specific CCR5 antagonist as determined in multiple receptor binding and signal transduction assays. This compound specifically inhibits HIV-1 infection mediated by CCR5 in U-87 astroglioma cells but has no effect on infection of CXCR4-expressing cells. SCH-C has broad and potent antiviral activity in vitro against primary HIV-1 isolates that use CCR5 as their entry coreceptor, with mean 50% inhibitory concentrations ranging between 0.4 and 9 nM. Moreover, SCH-C strongly inhibits the replication of an R5-using HIV-1 isolate in SCID-hu Thy/Liv mice. SCH-C has a favorable pharmacokinetic profile in rodents and primates with an oral bioavailability of 50-60% and a serum half-life of 5-6 h. On the basis of its novel mechanism of action, potent antiviral activity, and in vivo pharmacokinetic profile, SCH-C is a promising new candidate for therapeutic intervention of HIV infection.

  11. Challenge the science-stereotype. Der Einfluss von Technik-Freizeitkursen auf das Naturwissenschaften-Stereotyp von Schülerinnen und Schülern

    OpenAIRE

    Hannover, Bettina; Kessels, Ursula

    2002-01-01

    Der Aufsatz untersucht Aspekte von Kultur, die die individuelle Interessen- und Leistungsentwicklung von Schülerinnen und Schülern prägen ... . Es stehen die Kulturen spezifischer Schulfächer im Vordergrund. Im Aufsatz werden kulturell geteilte Annahmen über mathematisch- naturwissenschaftliche Schulfächer im Unterschied zu geistes- und sozialwissenschaftlichen Disziplinen untersucht; nämlich stereotype Vorstellungen über den Gegenstandsbereich, über Unterrichtsscripts, über typische Lehrpers...

  12. Mutual enhancement of central neurotoxicity induced by ketamine followed by methamphetamine

    International Nuclear Information System (INIS)

    Ke, J.-J.; Chen, H.-I.; Jen, C.J.; Kuo, Y.-M.; Cherng, C.G.; Tsai, Y.-P.N.; Ho, M.-C.; Tsai, C.-W.; Lung Yu

    2008-01-01

    We hereby report that repeated administration of ketamine (350 mg/kg in total) and methamphetamine (30 mg/kg in total) causes specific glutamatergic and dopaminergic neuron deficits, respectively, in adult mouse brain. Acute ketamine did not affect basal body temperature or the later methamphetamine-induced hyperthermia. However, pretreatment with repeated doses of ketamine aggravated methamphetamine-induced dopaminergic terminal loss as evidenced by a drastic decrease in the levels of dopamine, 3,4-dihydroxyphenylacetic acid, and dopamine transporter density as well as poor gait balance performance. In contrast, methamphetamine-induced serotonergic depletion was not altered by ketamine pretreatment. Likewise, the subsequent treatment with methamphetamine exacerbated the ketamine-induced glutamatergic damage as indicated by reduced levels of the vesicular glutamate transporter in hippocampus and striatum and poor memory performance in the Morris water maze. Finally, since activation of the D1 and AMPA/kainate receptors has been known to be involved in the release of glutamate and dopamine, we examined the effects of co-administration of SCH23390, a D1 antagonist, and CNQX, an AMPA/kainate antagonist. Intraventricular CNQX infusion abolished ketamine's potentiation of methamphetamine-induced dopamine neurotoxicity, while systemic SCH23390 mitigated methamphetamine's potentiation of ketamine-induced glutamatergic toxicity. We conclude that repeated doses of ketamine potentiate methamphetamine-induced dopamine neurotoxicity via AMPA/kainate activation and that conjunctive use of methamphetamine aggravates ketamine-induced glutamatergic neurotoxicity possibly via D1 receptor activation

  13. Medial prefrontal cortex lesions impair decision-making on a rodent gambling task: reversal by D1 receptor antagonist administration.

    Science.gov (United States)

    Paine, Tracie A; Asinof, Samuel K; Diehl, Geoffrey W; Frackman, Anna; Leffler, Joseph

    2013-04-15

    Decision-making is a complex cognitive process that is impaired in a number of psychiatric disorders. In the laboratory, decision-making is frequently assessed using "gambling" tasks that are designed to simulate real-life decisions in terms of uncertainty, reward and punishment. Here, we investigate whether lesions of the medial prefrontal cortex (PFC) cause impairments in decision-making using a rodent gambling task (rGT). In this task, rats have to decide between 1 of 4 possible options: 2 options are considered "advantageous" and lead to greater net rewards (food pellets) than the other 2 "disadvantageous" options. Once rats attained stable levels of performance on the rGT they underwent sham or excitoxic lesions of the medial PFC and were allowed to recover for 1 week. Following recovery, rats were retrained for 5 days and then the effects of a dopamine D1-like receptor antagonist (SCH23390) or a D2-like receptor antagonist (haloperidol) on performance were assessed. Lesioned rats exhibited impaired decision-making: they made fewer advantageous choices and chose the most optimal choice less frequently than did sham-operated rats. Administration of SCH23390 (0.03 mg/kg), but not haloperidol (0.015-0.03 mg/kg) attenuated the lesion-induced decision-making deficit. These results indicate that the medial PFC is important for decision-making and that excessive signaling at D1 receptors may contribute to decision-making impairments. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Tesofensine, a novel triple monoamine reuptake inhibitor, induces appetite suppression by indirect stimulation of alpha1 adrenoceptor and dopamine D1 receptor pathways in the diet-induced obese rat

    DEFF Research Database (Denmark)

    Axel, Anne Marie Dixen; Mikkelsen, Jens D; Hansen, Henrik H

    2010-01-01

    ) and partially antagonized by co-administration of SCH23390 (0.03 mg/kg, DA D(1) receptor antagonist). In contrast, tesofensine-induced hypophagia was not affected by RX821002 (0.3 mg/kg, alpha(2) adrenoceptor antagonist), haloperidol (0.03 mg/kg, D(2) receptor antagonist), NGB2904 (0.1 mg/kg, D(3) receptor...

  15. Characterization of D1 dopamine receptors in the central nervous system

    International Nuclear Information System (INIS)

    Hess, E.J.

    1987-01-01

    Several lines of evidence suggest an association of central nervous system dopaminergic systems in the etiology of the schizophrenia. Interest in the role of D 1 dopamine receptors has revived with the advent of selective drugs for this dopamine receptor, particularly the D 1 dopamine receptor antagonists, SCH23390. [ 3 H]SCH23390 represents a superior radioligand for labeling the two-state striatal D 1 dopamine receptor in that its high percent specific binding makes it especially suitable for detailed mechanistic studies of this receptor. Striatal D 1 dopamine receptors have been shown to mediate the stimulation of adenylate cyclase activity via a guanine nucleotide regulatory subunit. Forskolin acts in a synergistic manner with dopamine agonists, guanine nucleotides or sodium fluoride to potentiate the stimulation of rat striatal adenylate cyclase activity mediated by these reagents. By using the aforementioned reagents and the irreversible receptor modifying reagent N-ethoxycarbonyl-2-ethoxy-1,2,-dihydroquinoline, we demonstrated that the D 1 dopamine receptor population in rat striatum is not a stoichiometrically-limiting factor in agonist stimulation of adenylate cyclase activity

  16. Henoch-Schönlein purpura in an older man presenting as rectal bleeding and IgA mesangioproliferative glomerulonephritis: a case report

    OpenAIRE

    Howarth Charles B; Jirajariyavej Teeranun; Cheungpasitporn Wisit; Rosen Raquel M

    2011-01-01

    Abstract Introduction Henoch-Schönlein purpura is the most common systemic vasculitis in children. Typical presentations are palpable purpura, abdominal pain, arthritis, and hematuria. This vasculitic syndrome can present as an uncommon cause of rectal bleeding in older patients. We report a case of an older man with Henoch-Schönlein purpura. He presented with rectal bleeding and acute kidney injury secondary to IgA mesangioproliferative glomerulonephritis. Case presentation A 75-year-old Pol...

  17. Characteristics of stably expressed human dopamine D1a and D1b receptors: atypical behavior of the dopamine D1b receptor

    DEFF Research Database (Denmark)

    Pedersen, U B; Norby, B; Jensen, Anders A.

    1994-01-01

    Human dopamine D1a and D1b receptors were stably expressed in Baby Hamster Kidney (BHK) or Chinese Hamster Ovary (CHO) cells. [3H]SCH23390 saturation experiments indicated the presence of only a single binding site in the D1a expressing cell line with a Kd of 0.5 nM. In D1b expressing cell lines...

  18. Aufbau von regionalen Schülerforschungszentren Berichte und Praxisempfehlungen

    CERN Document Server

    Bayatloo, Annabel

    2013-01-01

    Angesichts des sich verschärfenden Fachkräftemangels ist es wichtig, die vorhandenen Begabungspotenziale noch wirkungsvoller zu identifizieren und auszuschöpfen. Vor allem im Bereich von Mathematik, Informatik, Naturwissenschaft und Technik (MINT) erweist es sich als zielführend, künftig stärker auf forschendes Lernen zu setzen. Dieser pädagogische Ansatz wird auf vorbildliche Weise an Schülerforschungszentren verwirklicht. Aufgrund der Chancen für die Nachwuchsförderung, die mit diesen außerschulischen MINT-Bildungszentren verbunden sind, haben der Deutsche Industrie- und Handelskammertag (DIHK), die IHK Darmstadt, LernortLabor - Bundesverband der Schülerlabore e. V. und die Stiftung Jugend forscht e. V. gemeinsam einen Leitfaden für den „Aufbau regionaler Schülerforschungszentren“ erarbeitet. Die neue Publikation ist als Best Practice-Handreichung konzipiert und soll vor allem regionale Entscheidungsträger in die Lage versetzen, auf diesem Feld selbst aktiv zu werden und den begonnenen Pr...

  19. Henoch-Schönlein Purpura Complicated by Hepatocellular Carcinoma.

    Science.gov (United States)

    Akizue, Naoki; Suzuki, Eiichiro; Yokoyama, Masayuki; Inoue, Masanori; Wakamatsu, Toru; Saito, Tomoko; Kusakabe, Yuko; Ogasawara, Sadahisa; Ooka, Yoshihiko; Tawada, Akinobu; Maru, Yugo; Matsue, Hiroyuki; Chiba, Tetsuhiro

    2017-11-15

    Although Henoch-Schönlein purpura (HSP) is known to be accompanied by malignancies, cases with hepatobiliary cancer are extremely rare. A 62-year-old man with palpable purpura rapidly extending to both lower legs was admitted to our hospital. He was undergoing follow-up for cirrhosis caused by chronic hepatitis B virus infection and hepatocellular carcinoma (HCC). He had renal dysfunction with hematuria and proteinuria and abdominal pain. Based on the clinical presentation and skin biopsy findings, he was diagnosed with HSP. The administration of steroids resulted in the rapid improvement of the patient's symptoms and he was discharged 12 days after admission.

  20. NMDA receptor antagonists inhibit catalepsy induced by either dopamine D1 or D2 receptor antagonists.

    Science.gov (United States)

    Moore, N A; Blackman, A; Awere, S; Leander, J D

    1993-06-11

    In the present study, we investigated the ability of NMDA receptor antagonists to inhibit catalepsy induced by haloperidol, or SCH23390 and clebopride, selective dopamine D1 and D2 receptor antagonists respectively. Catalepsy was measured by recording the time the animal remained with its forepaws placed over a rod 6 cm above the bench. Pretreatment with either the non-competitive NMDA receptor antagonist, MK-801 (0.25-0.5 mg/kg i.p.) or the competitive antagonist, LY274614 (10-20 mg/kg i.p.) reduced the cataleptic response produced by haloperidol (10 mg/kg), SCH23390 (2.5-10 mg/kp i.p.) or clebopride (5-20 mg/kg i.p.). This demonstrates that NMDA receptor antagonists will reduce both dopamine D1 and D2 receptor antagonist-induced catalepsy. Muscle relaxant doses of chlordiazepoxide (10 mg/kg i.p.) failed to reduce the catalepsy induced by haloperidol, suggesting that the anticataleptic effect of the NMDA receptor antagonists was not due to a non-specific action. These results support the hypothesis that NMDA receptor antagonists may have beneficial effects in disorders involving reduced dopaminergic function, such as Parkinson's disease.

  1. Agents that affect cAMP levels or protein kinase A activity modulate memory consolidation when injected into rat hippocampus but not amygdala

    Directory of Open Access Journals (Sweden)

    L. Bevilaqua

    1997-08-01

    Full Text Available Male Wistar rats were trained in one-trial step-down inhibitory avoidance using a 0.4-mA footshock. At various times after training (0, 1.5, 3, 6 and 9 h for the animals implanted into the CA1 region of the hippocampus; 0 and 3 h for those implanted into the amygdala, these animals received microinfusions of SKF38393 (7.5 µg/side, SCH23390 (0.5 µg/side, norepinephrine (0.3 µg/side, timolol (0.3 µg/side, 8-OH-DPAT (2.5 µg/side, NAN-190 (2.5 µg/side, forskolin (0.5 µg/side, KT5720 (0.5 µg/side or 8-Br-cAMP (1.25 µg/side. Rats were tested for retention 24 h after training. When given into the hippocampus 0 h post-training, norepinephrine enhanced memory whereas KT5720 was amnestic. When given 1.5 h after training, all treatments were ineffective. When given 3 or 6 h post-training, 8-Br-cAMP, forskolin, SKF38393, norepinephrine and NAN-190 caused memory facilitation, while KT5720, SCH23390, timolol and 8-OH-DPAT caused retrograde amnesia. Again, at 9 h after training, all treatments were ineffective. When given into the amygdala, norepinephrine caused retrograde facilitation at 0 h after training. The other drugs infused into the amygdala did not cause any significant effect. These data suggest that in the hippocampus, but not in the amygdala, a cAMP/protein kinase A pathway is involved in memory consolidation at 3 and 6 h after training, which is regulated by D1, ß, and 5HT1A receptors. This correlates with data on increased post-training cAMP levels and a dual peak of protein kinase A activity and CREB-P levels (at 0 and 3-6 h in rat hippocampus after training in this task. These results suggest that the hippocampus, but not the amygdala, is involved in long-term storage of step-down inhibitory avoidance in the rat.

  2. Das verfügbare Geld im Jugendalltag von 13- bis 17-jährigen Schülern und Schülerinnen: empirische Ergebnisse

    OpenAIRE

    Tully, Claus; Santen, Eric van

    2012-01-01

    "Prozesse der Bildung, Ablösung, Differenzierung und Positionierung gehören zur Verselbstständigung und zum Erwachsenwerden. Die Verfügung über Geld spielt dabei eine wichtige Rolle. Geld, als Voraussetzung für Konsum und damit Mittel, um 'im Spiel zu bleiben'. SchülerInnen verfügen über keine eigenen Einkünfte und sind auf Zuwendungen (Taschengeld und staatliche Transferleistungen wie Schüler-Bafög) oder selbst hinzu verdientes Geld angewiesen. Der Beitrag stellt empirische Ergebnisse zur Hö...

  3. The Aspergillus fumigatus SchASCH9 kinase modulates SakAHOG1 MAP kinase activity and it is essential for virulence.

    Science.gov (United States)

    Alves de Castro, Patrícia; Dos Reis, Thaila Fernanda; Dolan, Stephen K; Oliveira Manfiolli, Adriana; Brown, Neil Andrew; Jones, Gary W; Doyle, Sean; Riaño-Pachón, Diego M; Squina, Fábio Márcio; Caldana, Camila; Singh, Ashutosh; Del Poeta, Maurizio; Hagiwara, Daisuke; Silva-Rocha, Rafael; Goldman, Gustavo H

    2016-11-01

    The serine-threonine kinase TOR, the Target of Rapamycin, is an important regulator of nutrient, energy and stress signaling in eukaryotes. Sch9, a Ser/Thr kinase of AGC family (the cAMP-dependent PKA, cGMP- dependent protein kinase G and phospholipid-dependent protein kinase C family), is a substrate of TOR. Here, we characterized the fungal opportunistic pathogen Aspergillus fumigatus Sch9 homologue (SchA). The schA null mutant was sensitive to rapamycin, high concentrations of calcium, hyperosmotic stress and SchA was involved in iron metabolism. The ΔschA null mutant showed increased phosphorylation of SakA, the A. fumigatus Hog1 homologue. The schA null mutant has increased and decreased trehalose and glycerol accumulation, respectively, suggesting SchA performs different roles for glycerol and trehalose accumulation during osmotic stress. The schA was transcriptionally regulated by osmotic stress and this response was dependent on SakA and MpkC. The double ΔschA ΔsakA and ΔschA ΔmpkC mutants were more sensitive to osmotic stress than the corresponding parental strains. Transcriptomics and proteomics identified direct and indirect targets of SchA post-exposure to hyperosmotic stress. Finally, ΔschA was avirulent in a low dose murine infection model. Our results suggest there is a complex network of interactions amongst the A. fumigatus TOR, SakA and SchA pathways. © 2016 John Wiley & Sons Ltd.

  4. The possible interaction of dopamine system in nucleus accumbens shell and glutamate system of prelimbic region on locomotor activity in rat

    Directory of Open Access Journals (Sweden)

    Hatam Ahmadi

    2013-06-01

    Full Text Available Background: Nucleus accumbens (NAc and prefrontal cortex (PFC dopaminergic and glutamatergic systems are involved in regulating of locomotor activity behaviors. This study has investigated the interaction of NAc shell dopaminergic system and prelimbic glutamatergic systems in regulating locomotor activity and related parameters. Methods: The aim of this study was the effect the drugs injection interaction in the brain of male Wistar rats on locomotor activity and related parameters, in the order of this purpose, open field apparatus that automatically recorded locomotor activity was employed. Unilateral intra-cerebral injection of drugs was done. Results: Unilateral intra-prelimbic injection of D-AP7 (N-methyl-D-aspartic acid= NMDA receptor antagonist; 0.25, 0.5 and 1μg/μl did not alter locomotor activity behaviors. However, infusion of NMDA (0.9μg/μl in this region increased locomotor activity (P<0.01, whereas decreased rearing (P<0.01 and grooming (P<0.01 which was blocked by D-AP7 (0.25μg/μl (P<0.01. Moreover, unilateral infusion of SCH23390 (dopamine D1 receptor antagonist; 0.25, 0.5 and 1μg/μl into the left NAc shell did not alter locomotor activity. However, injection of SKF38393 (dopamine D1 receptor agonist; 4μg/μl into the left NAc shell increased locomotor activity (P<0.05 which was blocked by SCH23390 (0.25μg/μl (P<0.01. Furthermore, the subthreshold dose infusion of SCH23390 (0.25μg/μl into the left NAc shell reduced the effect of intra- prelimbic NMDA on locomotor activity (P<0.01. In addition, intra-NAc shell administration of the subthreshold dose of SKF38393 (1μg/μl potentiated the middle dose (P<0.05, whereas decreased the higher dose of intra-left prelimbic NMDA response (P<0.05 on locomotor activity. Conclusion: The results suggested a modulatory effect of the NAc shell dopaminergic system on increased locomotor activity by activating glutamate system in prelimbic.

  5. Gianturco-Rösch Z stents in tracheobronchial stenoses.

    Science.gov (United States)

    Petersen, B D; Uchida, B T; Barton, R E; Keller, F S; Rösch, J

    1995-01-01

    To evaluate expandable metallic Gianturco-Rösch Z (GRZ) stents for treatment of benign and malignant tracheobronchial stenoses. Six patients, ages 45-73 years, were treated for severe dyspnea with placement of GRZ stents. Three patients had benign tracheal lesions (one tracheomalacia, two postoperative) and received uncovered GRZ stents. Three patients had malignant stenoses at the level of the carina; one received an uncovered stent and the other two received silicone-covered GRZ stents. Two patients with benign lesions responded well to stent placement. One was asymptomatic for a year and then was lost to follow-up; the other improved substantially but died of end-stage lung disease 5 months after stent placement. A third patient with a benign high tracheal lesion did poorly; symptoms recurred secondary to inferior migration of a stent, which was removed surgically at 4 months. All patients with malignant lesions improved symptomatically after stent placement and remained without significant dyspnea until death (from 1 to 6 months). Expandable GRZ stents are promising devices for treatment of benign lesions and offer effective palliation of malignant tracheobronchial stenoses.

  6. Die Schönbuchbahn. Von der Nebenbahn zum S-Bahn-Standard

    Science.gov (United States)

    Brauer, Tobias

    2017-09-01

    Since the successful reactivation of the schönbuch railway between Böblingen and Dettenhausen the number of passengers has increased continuously. Due to this high demand of over 8000 people per day and the increase of popularity the current expansion projects include the electrification of the 17 km long track and the installation of double-track sections for providing a 15-minute-service between Böblingen and Holzgerlingen. To realize the new operational concept, Zweckverband Schönbuchbahn (ZVS), the public transport authority, has ordered nine light rail-styled vehicles (with costs around 51,3 mio. euro for developing and construction). In this way the schönbuch railway is an important factor to guarantee a sustainable and forward-looking mobility in the metropolitan area of Stuttgart and for restricting car traffic.

  7. Molecular structures of Se(SCH3)2 and Te(SCH3)2 using gas-phase electron diffraction and ab initio and DFT geometry optimisations.

    Science.gov (United States)

    Fleischer, Holger; Wann, Derek A; Hinchley, Sarah L; Borisenko, Konstantin B; Lewis, James R; Mawhorter, Richard J; Robertson, Heather E; Rankin, David W H

    2005-10-07

    The molecular structures of Se(SCH(3))(2) and Te(SCH(3))(2) were investigated using gas-phase electron diffraction (GED) and ab initio and DFT geometry optimisations. While parameters involving H atoms were refined using flexible restraints according to the SARACEN method, parameters that depended only on heavy atoms could be refined without restraints. The GED-determined geometric parameters (r(h1)) are: rSe-S 219.1(1), rS-C 183.2(1), rC-H 109.6(4) pm; angleS-Se-S 102.9(3), angleSe-S-C 100.6(2), angleS-C-H (mean) 107.4(5), phiS-Se-S-C 87.9(20), phiSe-S-C-H 178.8(19) degrees for Se(SCH(3))(2), and rTe-S 238.1(2), rS-C 184.1(3), rC-H 110.0(6) pm; angleS-Te-S 98.9(6), angleTe-S-C 99.7(4), angleS-C-H (mean) 109.2(9), phiS-Te-S-C 73.0(48), phiTe-S-C-H 180.1(19) degrees for Te(SCH(3))(2). Ab initio and DFT calculations were performed at the HF, MP2 and B3LYP levels, employing either full-electron basis sets [3-21G(d) or 6-31G(d)] or an effective core potential with a valence basis set [LanL2DZ(d)]. The best fit to the GED structures was achieved at the MP2 level. Differences between GED and MP2 results for rS-C and angleS-Te-S were explained by the thermal population of excited vibrational states under the experimental conditions. All theoretical models agreed that each compound exists as two stable conformers, one in which the methyl groups are on the same side (g(+)g(-) conformer) and one in which they are on different sides (g(+)g(+) conformer) of the S-Y-S plane (Y = Se, Te). The conformational composition under the experimental conditions could not be resolved from the GED data. Despite GED R-factors and ab initio and DFT energies favouring the g(+)g(+) conformer, it is likely that both conformers are present, for Se(SCH(3))(2) as well as for Te(SCH(3))(2).

  8. Subclinical hypothyroidism is associated with increased risk for all-cause and cardiovascular mortality in adults.

    Science.gov (United States)

    Tseng, Fen-Yu; Lin, Wen-Yuan; Lin, Cheng-Chieh; Lee, Long-Teng; Li, Tsai-Chung; Sung, Pei-Kun; Huang, Kuo-Chin

    2012-08-21

    This study sought to evaluate the relationship between subclinical hypothyroidism (SCH) and all-cause and cardiovascular disease (CVD) mortality. SCH may increase the risks of hypercholesterolemia and atherosclerosis. The associations between SCH and all-cause or CVD mortality are uncertain, on the basis of the results of previous studies. A baseline cohort of 115,746 participants without a history of thyroid disease, ≥20 years of age, was recruited in Taiwan. SCH was defined as a serum thyroid-stimulating hormone (TSH) level of 5.0 to 19.96 mIU/l with normal total thyroxine concentrations. Euthyroidism was defined as a serum TSH level of 0.47 to 4.9 mIU/l. Cox proportional hazards regression analysis was used to estimate the relative risks (RRs) of death from all-cause and CVD for adults with SCH during a 10-year follow-up period. There were 3,669 deaths during the follow-up period; 680 deaths were due to CVD. Compared with subjects with euthyroidism, after adjustment for age, sex, body mass index, diabetes, hypertension, dyslipidemia, smoking, alcohol consumption, betel nut chewing, physical activity, income, and education level, the RRs (95% confidence interval) of deaths from all-cause and CVD among subjects with SCH were 1.30 (1.02 to 1.66), and 1.68 (1.02 to 2.76), respectively. Adult Taiwanese with SCH had an increased risk for all-cause mortality and CVD death. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  9. Efficacy of SCH27899 in an Animal Model of Legionnaires' Disease Using Immunocompromised A/J Mice

    Science.gov (United States)

    Brieland, Joan K.; Loebenberg, David; Menzel, Fred; Hare, Roberta S.

    2000-01-01

    The efficacy of SCH27899, a new everninomicin antibiotic, against replicative Legionella pneumophila lung infections in an immunocompromised host was evaluated using a murine model of Legionnaires' disease. A/J mice were immunocompromised with cortisone acetate and inoculated intratracheally with L. pneumophila serogroup 1 (105 CFU per mouse). At 24 h postinoculation, mice were administered either SCH27899 (6 to 60 mg/kg [MPK] intravenously) or a placebo once daily for 5 days, and mortality and intrapulmonary growth of L. pneumophila were assessed. In the absence of SCH27899, there was 100% mortality in L. pneumophila-infected mice, with exponential intrapulmonary growth of the bacteria. In contrast, administration of SCH27899 at a dose of ≥30 MPK resulted in ≥90% survival of infected mice, which was associated with inhibition of intrapulmonary growth of L. pneumophila. In subsequent studies, the efficacy of SCH27899 was compared to ofloxacin (OFX) and azithromycin (AZI). Administration of SCH27899, OFX, or AZI at a dose of ≥30 MPK once daily for 5 days resulted in ≥85% survival of infected mice and inhibition of intrapulmonary growth of the bacteria. However, L. pneumophila CFU were recovered in lung homogenates following cessation of therapy with all three antibiotics. These studies demonstrate that SCH27899 effectively prevents fatal replicative L. pneumophila lung infection in immunocompromised A/J mice by inhibition of intrapulmonary growth of the bacteria. However, in this murine model of pulmonary legionellosis, SCH27899, like OFX and AZI, was bacteriostatic. PMID:10770771

  10. Role of the brain dopaminergic and opioid system in the regulation of "child's" (maternal bonding) behavior of newborn albino rats.

    Science.gov (United States)

    Stovolosov, I S; Dubynin, V A; Kamensky, A A

    2011-01-01

    Administration of D(2) receptor antagonist clebopride in a dose not affecting locomotor activity was followed by a decrease in maternal bonding behavior of 10-day-old and 15-day-old albino rat pups. D(1) receptor antagonist SCH23390 had a stimulatory effect only on the behavior of 10-day-old newborns. Opioid peptide β-casomorphin-7 abolished the effect of clebopride in rat pups of the older age group.

  11. SchNet - A deep learning architecture for molecules and materials

    Science.gov (United States)

    Schütt, K. T.; Sauceda, H. E.; Kindermans, P.-J.; Tkatchenko, A.; Müller, K.-R.

    2018-06-01

    Deep learning has led to a paradigm shift in artificial intelligence, including web, text, and image search, speech recognition, as well as bioinformatics, with growing impact in chemical physics. Machine learning, in general, and deep learning, in particular, are ideally suitable for representing quantum-mechanical interactions, enabling us to model nonlinear potential-energy surfaces or enhancing the exploration of chemical compound space. Here we present the deep learning architecture SchNet that is specifically designed to model atomistic systems by making use of continuous-filter convolutional layers. We demonstrate the capabilities of SchNet by accurately predicting a range of properties across chemical space for molecules and materials, where our model learns chemically plausible embeddings of atom types across the periodic table. Finally, we employ SchNet to predict potential-energy surfaces and energy-conserving force fields for molecular dynamics simulations of small molecules and perform an exemplary study on the quantum-mechanical properties of C20-fullerene that would have been infeasible with regular ab initio molecular dynamics.

  12. Schéma directeur des Systèmes d'information 2012-2016

    OpenAIRE

    Institut National de Recherche Agronomique UAR 0776 Administration du siège

    2012-01-01

    Le schéma directeur des systèmes d’information de l’inra est le premier Schéma directeur dont l’institut se dote dans le champ des systèmes D’information. Il couvre la période 2012‐2016 du contrat d’objectifs Et s’inscrit dans les perspectives scientifiques dressées par le document D’orientation 2010‐2020

  13. Hyperactivity induced by stimulation of separate dopamine D-1 and D-2 receptors in rats with bilateral 6-OHDA lesions.

    Science.gov (United States)

    Arnt, J

    1985-08-26

    The effects of DA agonists and antagonists with different dopamine (DA) D-1 and D-2 receptor selectivity have been studied in rats with bilateral 6-OHDA lesions. The D-1 agonist SK & F 38393, the D-2 agonist pergolide and the mixed agonist apomorphine all induced marked hyperactivity in lesioned rats in doses which were without stimulant effect in sham-operated animals. The hyperactivity induced by SK & F 38393 was blocked by the DA D-1 antagonist SCH 23390, but unaffected by the D-2 antagonists spiroperidol or clebopride. Pergolide-induced hyperactivity showed the reverse selectivity. The mixed D-1/D-2 antagonists, cis(Z)-flupentixol and cis(Z)-clopenthixol, however blocked the effect of both agonists. Apomorphine-induced hyperactivity was neither blocked by selective D-1 nor D-2 antagonists, but was dose-dependently inhibited by cis(Z)-flupentixol and cis(Z)-clopenthixol. Potent blockade was also obtained by combined treatment with SCH 23390 and spiroperidol, indicating the need of blocking both D-1 and D-2 receptors simultaneously. The results indicate that D-1 and D-2 receptor function can be independently manipulated in denervated rats and they confirm similar results obtained in rats with unilateral 6-OHDA lesions using circling behaviour.

  14. Simultaneous Multiple MS Binding Assays Addressing D1 and D2 Dopamine Receptors.

    Science.gov (United States)

    Schuller, Marion; Höfner, Georg; Wanner, Klaus T

    2017-10-09

    MS Binding Assays are a label-free alternative to radioligand binding assays. They provide basically the same capabilities as the latter, but use a non-labeled reporter ligand instead of a radioligand. In contrast to radioligand binding assays, MS Binding Assays offer-owing to the selectivity of mass spectrometric detection-the opportunity to monitor the binding of different reporter ligands at different targets simultaneously. The present study shows a proof of concept for this strategy as exemplified for MS Binding Assays selectively addressing D 1 and D 2 dopamine receptors in a single binding experiment. A highly sensitive, rapid and robust LC-ESI-MS/MS quantification method capable of quantifying both SCH23390 and raclopride, selectively addressing D 1 and D 2 receptors, respectively, was established and validated for this purpose. Based thereon, simultaneous saturation and competition experiments with SCH23390 and raclopride in the presence of both D 1 and D 2 receptors were performed and analyzed by LC-MS/MS within a single chromatographic cycle. The present study thus demonstrates the feasibility of this strategy and the high versatility of MS Binding Assays that appears to surpass that common for conventional radioligand binding assays. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Local application of SCH 39166 reversibly and dose-dependently decreases acetylcholine release in the rat striatum.

    Science.gov (United States)

    Acquas, E; Di Chiara, G

    1999-11-03

    The effect of local application by reverse dialysis of the dopamine D(1) receptor antagonist (-)-trans-6,7,7a,8,9, 13b-exahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo-[d]-nap hto-[2, 1b]-azepine hydrochloride (SCH 39166) on acetylcholine release was studied in awake, freely moving rats implanted with concentric microdialysis probes in the dorsal striatum. In these experiments, the reversible acetylcholine esterase inhibitor, neostigmine, was added to the perfusion solution at two different concentrations, 0.01 and 0.1 microM. SCH 39166 (1, 5 and 10 microM), in the presence of 0.01 microM neostigmine, reversibly decreased striatal acetylcholine release (1 microM SCH 39166 by 8+/-4%; 5 microM SCH 39166 by 24+/-5%; 10 microM SCH 39166 by 27+/-7%, from basal). Similarly, SCH 39166, applied in the presence of a higher neostigmine concentration (0.1 microM), decreased striatal acetylcholine release by 14+/-4% at 1 microM, by 28+/-8% at 5 microM and by 30+/-5% at 10 microM, in a dose-dependent and time-dependent manner. These results are consistent with the existence of a facilitatory tone of dopamine on striatal acetylcholine transmission mediated by dopamine D(1) receptors located on striatal cholinergic interneurons.

  16. Henoch-Schönlein purpura with intracerebral haemorrhage in an adult patient: a case report

    Directory of Open Access Journals (Sweden)

    Karamadoukis Lazarus

    2008-06-01

    Full Text Available Abstract Introduction Henoch-Schönlein purpura is a small vessel vasculitis that affects mainly the skin, joints, gastrointestinal tract and kidneys. The central nervous system is also occasionally affected, although the majority of patients experience only mild symptoms such as headaches and behavioural changes. Intracerebral haemorrhage is a rare complication of Henoch-Schönlein purpura that so far has mainly been described in children and young adolescence. Case presentation We describe a 42-year-old man with Henoch-Schönlein purpura who developed an acute intracerebral haemorrhage that coincided with a reactivation of his vasculitis and the development of renal failure following discontinuation of steroids. In this patient, both the Henoch-Schönlein purpura and his neurological symptoms were successfully treated with intravenous cyclophosphamide and methylprednisolone, followed by a short course of oral cyclophosphamide and long-term oral prednisolone. His renal function also recovered sufficiently not to require renal replacement therapy. Conclusion The management of Henoch-Schönlein nephritis remains unclear, especially in the presence of severe complications such as intracerebral haemorrhage. We describe a successful outcome in such a patient.

  17. Excavations at Schöningen and paradigm shifts in human evolution.

    Science.gov (United States)

    Conard, Nicholas J; Serangeli, Jordi; Böhner, Utz; Starkovich, Britt M; Miller, Christopher E; Urban, Brigitte; Van Kolfschoten, Thijs

    2015-12-01

    The exceptional preservation at Schöningen together with a mixture of perseverance, hard work, and sheer luck led to the recovery of unique finds in an exceptional context. The 1995 discovery of numerous wooden artifacts, most notably at least 10 carefully made spears together with the skeletons of at least 20 to 25 butchered horses, brought the debate about hunting versus scavenging among late archaic hominins and analogous arguments about the purportedly primitive behavior of Homo heidelbergensis and Neanderthals to an end. Work under H. Thieme's lead from 1992 to 2008 and results from the current team since 2008 demonstrate that late H. heidelbergensis or early Neanderthals used sophisticated artifacts made from floral and faunal materials, in addition to lithic artifacts more typically recovered at Lower Paleolithic sites. The finds from the famous Horse Butchery Site and two dozen other archaeological horizons from the edges of the open-cast mine at Schöningen provide many new insights into the technology and behavioral patterns of hominins about 300 ka BP during MIS 9 on the Northern European Plain. An analysis of the finds from Schöningen and their contexts shows that the inhabitants of the site were skilled hunters at the top of the food chain and exhibited a high level of planning depth. These hominins had command of effective means of communication about the here and now, and the past and the future, that allowed them to repeatedly execute well-coordinated and successful group activities that likely culminated in a division of labor and social and economic patterns radically different from those of all non-human primates. The unique preservation and high quality excavations have led to a major paradigm shift or "Schöningen Effect" that changed our views of human evolution during the late Lower Paleolithic. In this respect, we can view the behaviors documented at Schöningen as a plausible baseline for the behavioral sophistication of archaic hominins

  18. The Creative Side of the Reflective Planner. Updating the Schön’s Findings

    Directory of Open Access Journals (Sweden)

    Maria Rosaria Stufano Melone

    2014-05-01

    Full Text Available The self-reflection on their own work has always been present in all designers, including architects and planners. In the mid 80-90 Donald Schön has made more explicit this aspect, which until then had not found a systematic scientific treatment.  The results of Schön are the basis of practical planning of the 90s period. However, the Schön's analysis reveals a context of knowledge of mental functioning typical of the conceiving period. From the 90s until now numerous advances in knowledge of the mechanisms of rationality, reflection and creativity have been made, and in this context we are interested in the progress made in the field of creativity.  We try to integrate and update the Schön's reflection with the new available theories such as the CK theory to offer planners a more innovated range of tools in order to understand and make better use of their creativity and self-reflection about their own creativity.

  19. Dopamine antagonists and brief vision distinguish lens-induced- and form-deprivation-induced myopia.

    Science.gov (United States)

    Nickla, Debora L; Totonelly, Kristen

    2011-11-01

    In eyes wearing negative lenses, the D2 dopamine antagonist spiperone was only partly effective in preventing the ameliorative effects of brief periods of vision (Nickla et al., 2010), in contrast to reports from studies using form-deprivation. The present study was done to directly compare the effects of spiperone, and the D1 antagonist SCH-23390, on the two different myopiagenic paradigms. 12-day old chickens wore monocular diffusers (form-deprivation) or -10 D lenses attached to the feathers with matching rings of Velcro. Each day for 4 days, 10 μl intravitreal injections of the dopamine D2/D4 antagonist spiperone (5 nmoles) or the D1 antagonist SCH-23390, were given under isoflurane anesthesia, and the diffusers (n = 16; n = 5, respectively) or lenses (n = 20; n = 6) were removed for 2 h immediately after. Saline injections prior to vision were done as controls (form-deprivation: n = 11; lenses: n = 10). Two other saline-injected groups wore the lenses (n = 12) or diffusers (n = 4) continuously. Axial dimensions were measured by high frequency A-scan ultrasonography at the start, and on the last day immediately prior to, and 3 h after the injection. Refractive errors were measured at the end of the experiment using a Hartinger's refractometer. In form-deprived eyes, spiperone, but not SCH-23390, prevented the ocular growth inhibition normally effected by the brief periods of vision (change in vitreous chamber depth, spiperone vs saline: 322 vs 211 μm; p = 0.01). By contrast, neither had any effect on negative lens-wearing eyes given similar unrestricted vision (210 and 234 μm respectively, vs 264 μm). The increased elongation in the spiperone-injected form-deprived eyes did not, however, result in a myopic shift, probably due to the inhibitory effect of the drug on anterior chamber growth (drug vs saline: 96 vs 160 μm; p effects of brief periods of unrestricted vision differ for form-deprivation versus negative lens-wear, which may imply different growth

  20. Lipid Signaling via Pkh1/2 Regulates Fungal CO2 Sensing through the Kinase Sch9

    Directory of Open Access Journals (Sweden)

    Susann Pohlers

    2017-01-01

    Full Text Available Adaptation to alternating CO2 concentrations is crucial for all organisms. Carbonic anhydrases—metalloenzymes that have been found in all domains of life—enable fixation of scarce CO2 by accelerating its conversion to bicarbonate and ensure maintenance of cellular metabolism. In fungi and other eukaryotes, the carbonic anhydrase Nce103 has been shown to be essential for growth in air (~0.04% CO2. Expression of NCE103 is regulated in response to CO2 availability. In Saccharomyces cerevisiae, NCE103 is activated by the transcription factor ScCst6, and in Candida albicans and Candida glabrata, it is activated by its homologues CaRca1 and CgRca1, respectively. To identify the kinase controlling Cst6/Rca1, we screened an S. cerevisiae kinase/phosphatase mutant library for the ability to regulate NCE103 in a CO2-dependent manner. We identified ScSch9 as a potential ScCst6-specific kinase, as the sch9Δ mutant strain showed deregulated NCE103 expression on the RNA and protein levels. Immunoprecipitation revealed the binding capabilities of both proteins, and detection of ScCst6 phosphorylation by ScSch9 in vitro confirmed Sch9 as the Cst6 kinase. We could show that CO2-dependent activation of Sch9, which is part of a kinase cascade, is mediated by lipid/Pkh1/2 signaling but not TORC1. Finally, we tested conservation of the identified regulatory cascade in the pathogenic yeast species C. albicans and C. glabrata. Deletion of SCH9 homologues of both species impaired CO2-dependent regulation of NCE103 expression, which indicates a conservation of the CO2 adaptation mechanism among yeasts. Thus, Sch9 is a Cst6/Rca1 kinase that links CO2 adaptation to lipid signaling via Pkh1/2 in fungi.

  1. The H+/K+ ATPase Inhibitor SCH-28080 Inhibits Insulin Secretion and Induces Cell Death in INS-1E Rat Insulinoma Cells

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    Martin Jakab

    2017-10-01

    was unaffected. The L-type ICav blocker nifedipine caused a full inhibition of GSIS at 10 and 20 µM. At 20 µM, SCH-28080 inhibited ICav comparable to 20 µM nifedipine and in addition augmented IKATP recorded at -60 mV and hyperpolarized Vmem by ∼15 mV. Cell viability 2 and 24 h post treatment with SCH-28080 was dose-dependently inhibited with IC50 values of 22.9 µM and 15.3 µM, respectively. At 20 µM the percentages of Annexin-V+, caspase+ and propidium iodide+ cells were significantly increased after 24 and 48 h. Concurrently, the MCV was significantly decreased (apoptotic volume decrease, AVD and the SSC signal was increased. At concentrations >40–50 µM, SCH-28080 became progressively cytotoxic causing a steep increase in necrotic cells already 2 h post treatment and a breakdown of ΔΨm within 4 h under 50 and 100 µM while 10 and 20 µM had no effect on ΔΨm within 24 h. Conclusion: We demonstrate expression of HKα2 in rat INS-1E cells. However, the pump is apparently non-functional under the given conditions. Nonetheless the H+/K+ ATPase blocker SCH-28080 inhibits insulin secretion and induces cell death. Importantly, we show that SCH-28080 inhibits ICav - and activates KATP channels identifying them as novel “off-targets” of the inhibitor, causing hyperpolarization of Vmem and inhibition of insulin secretion.

  2. Involvement of dopamine D1/D2 receptors on harmane-induced amnesia in the step-down passive avoidance test.

    Science.gov (United States)

    Nasehi, Mohammad; Piri, Morteza; Nouri, Maryam; Farzin, Davood; Nayer-Nouri, Touraj; Zarrindast, Mohammad Reza

    2010-05-25

    Ingestion of harmane and other alkaloids derived from plant Peganum harmala has been shown to elicit profound behavioural and toxic effects in humans, including hallucinations, excitation, feelings of elation, and euphoria. These alkaloids in the high doses can cause a toxic syndrome characterized by tremors and convulsions. Harmane has also been shown to act on a variety of receptor systems in the mammalian brain, including those for serotonin, dopamine and benzodiazepines. In animals, it has been reported to affect short and long term memory. In the present study, effects of dopamine D1 and D2 receptor antagonists on the harmane (HA)-induced amnesia and exploratory behaviors were examined in mice. One-trial step-down and hole-board paradigms were used for the assessment of memory retention and exploratory behaviors in adult male NMRI mice respectively. Intraperitoneal (i.p.) administration of HA (5 and 10 mg/kg) immediately after training decreased memory consolidation, while had no effect on anxiety-like behavior. Memory retrieval was not altered by 15- or 30 min pre-testing administration of the D1 (SCH23390, 0.025, 0.05 and 0.1 mg/kg) or D2 (sulpiride 12.5, 25 and 50 mg/kg) receptor antagonists, respectively. In contrast, SCH23390 (0.05 and 0.1 mg/kg) or sulpiride (25 and 50 mg/kg) pre-test administration fully reversed HA-induced impairment of memory consolidation. Finally, neither D1 nor D2 receptor blockade affected exploratory behaviors in the hole-board paradigm. Altogether, these findings strongly suggest an involvement of D1 and D2 receptors modulation in the HA-induced impairment of memory consolidation. Copyright 2010 Elsevier B.V. All rights reserved.

  3. Dextroamphetamine (but Not Atomoxetine Induces Reanimation from General Anesthesia: Implications for the Roles of Dopamine and Norepinephrine in Active Emergence.

    Directory of Open Access Journals (Sweden)

    Jonathan D Kenny

    Full Text Available Methylphenidate induces reanimation (active emergence from general anesthesia in rodents, and recent evidence suggests that dopaminergic neurotransmission is important in producing this effect. Dextroamphetamine causes the direct release of dopamine and norepinephrine, whereas atomoxetine is a selective reuptake inhibitor for norepinephrine. Like methylphenidate, both drugs are prescribed to treat Attention Deficit Hyperactivity Disorder. In this study, we tested the efficacy of dextroamphetamine and atomoxetine for inducing reanimation from general anesthesia in rats. Emergence from general anesthesia was defined by return of righting. During continuous sevoflurane anesthesia, dextroamphetamine dose-dependently induced behavioral arousal and restored righting, but atomoxetine did not (n = 6 each. When the D1 dopamine receptor antagonist SCH-23390 was administered prior to dextroamphetamine under the same conditions, righting was not restored (n = 6. After a single dose of propofol (8 mg/kg i.v., the mean emergence times for rats that received normal saline (vehicle and dextroamphetamine (1 mg/kg i.v. were 641 sec and 404 sec, respectively (n = 8 each. The difference was statistically significant. Although atomoxetine reduced mean emergence time to 566 sec (n = 8, this decrease was not statistically significant. Spectral analysis of electroencephalogram recordings revealed that dextroamphetamine and atomoxetine both induced a shift in peak power from δ (0.1-4 Hz to θ (4-8 Hz during continuous sevoflurane general anesthesia, which was not observed when animals were pre-treated with SCH-23390. In summary, dextroamphetamine induces reanimation from general anesthesia in rodents, but atomoxetine does not induce an arousal response under the same experimental conditions. This supports the hypothesis that dopaminergic stimulation during general anesthesia produces a robust behavioral arousal response. In contrast, selective noradrenergic stimulation

  4. Dextroamphetamine (but Not Atomoxetine) Induces Reanimation from General Anesthesia: Implications for the Roles of Dopamine and Norepinephrine in Active Emergence

    Science.gov (United States)

    Kenny, Jonathan D.; Taylor, Norman E.; Brown, Emery N.; Solt, Ken

    2015-01-01

    Methylphenidate induces reanimation (active emergence) from general anesthesia in rodents, and recent evidence suggests that dopaminergic neurotransmission is important in producing this effect. Dextroamphetamine causes the direct release of dopamine and norepinephrine, whereas atomoxetine is a selective reuptake inhibitor for norepinephrine. Like methylphenidate, both drugs are prescribed to treat Attention Deficit Hyperactivity Disorder. In this study, we tested the efficacy of dextroamphetamine and atomoxetine for inducing reanimation from general anesthesia in rats. Emergence from general anesthesia was defined by return of righting. During continuous sevoflurane anesthesia, dextroamphetamine dose-dependently induced behavioral arousal and restored righting, but atomoxetine did not (n = 6 each). When the D1 dopamine receptor antagonist SCH-23390 was administered prior to dextroamphetamine under the same conditions, righting was not restored (n = 6). After a single dose of propofol (8 mg/kg IV), the mean emergence times for rats that received normal saline (vehicle) and dextroamphetamine (1 mg/kg IV) were 641 sec and 404 sec, respectively (n = 8 each). The difference was statistically significant. Although atomoxetine reduced mean emergence time to 566 sec (n = 8), this decrease was not statistically significant. Spectral analysis of electroencephalogram recordings revealed that dextroamphetamine and atomoxetine both induced a shift in peak power from δ (0.1–4 Hz) to θ (4–8 Hz) during continuous sevoflurane general anesthesia, which was not observed when animals were pre-treated with SCH-23390. In summary, dextroamphetamine induces reanimation from general anesthesia in rodents, but atomoxetine does not induce an arousal response under the same experimental conditions. This supports the hypothesis that dopaminergic stimulation during general anesthesia produces a robust behavioral arousal response. In contrast, selective noradrenergic stimulation causes

  5. Dextroamphetamine (but Not Atomoxetine) Induces Reanimation from General Anesthesia: Implications for the Roles of Dopamine and Norepinephrine in Active Emergence.

    Science.gov (United States)

    Kenny, Jonathan D; Taylor, Norman E; Brown, Emery N; Solt, Ken

    2015-01-01

    Methylphenidate induces reanimation (active emergence) from general anesthesia in rodents, and recent evidence suggests that dopaminergic neurotransmission is important in producing this effect. Dextroamphetamine causes the direct release of dopamine and norepinephrine, whereas atomoxetine is a selective reuptake inhibitor for norepinephrine. Like methylphenidate, both drugs are prescribed to treat Attention Deficit Hyperactivity Disorder. In this study, we tested the efficacy of dextroamphetamine and atomoxetine for inducing reanimation from general anesthesia in rats. Emergence from general anesthesia was defined by return of righting. During continuous sevoflurane anesthesia, dextroamphetamine dose-dependently induced behavioral arousal and restored righting, but atomoxetine did not (n = 6 each). When the D1 dopamine receptor antagonist SCH-23390 was administered prior to dextroamphetamine under the same conditions, righting was not restored (n = 6). After a single dose of propofol (8 mg/kg i.v.), the mean emergence times for rats that received normal saline (vehicle) and dextroamphetamine (1 mg/kg i.v.) were 641 sec and 404 sec, respectively (n = 8 each). The difference was statistically significant. Although atomoxetine reduced mean emergence time to 566 sec (n = 8), this decrease was not statistically significant. Spectral analysis of electroencephalogram recordings revealed that dextroamphetamine and atomoxetine both induced a shift in peak power from δ (0.1-4 Hz) to θ (4-8 Hz) during continuous sevoflurane general anesthesia, which was not observed when animals were pre-treated with SCH-23390. In summary, dextroamphetamine induces reanimation from general anesthesia in rodents, but atomoxetine does not induce an arousal response under the same experimental conditions. This supports the hypothesis that dopaminergic stimulation during general anesthesia produces a robust behavioral arousal response. In contrast, selective noradrenergic stimulation causes

  6. Raamatuautomaadid Hamburgis / A. Bösch ; refereerinud Lea Laurberg-Heckelmann

    Index Scriptorium Estoniae

    Bösch, A.

    2012-01-01

    Refereeritud väljaandest: Bösch, A. Eine Schachtel Literatur ziehen: Bettina von Bülow betreibt in Hamburg Bücherautomaten - Das Angebot reicht vom Comics bis zum Stadtführer. - Lübecker Nachrichten, 30./31.10.2011, lk. 19

  7. Autoradiographic analysis of regional alterations in brain receptors following chronic administration and withdrawal of typical and atypical neuroleptics in rats

    International Nuclear Information System (INIS)

    See, R.E.; Ellison, G.; Toga, A.W.

    1990-01-01

    Rats were administered haloperidol, clozapine, raclopride, or no drug for 28 days or 8 months. Following a 3 week withdrawal period, in vitro autoradiography was utilized to examine receptor binding for dopamine D2([ 3 H]spiperone and [ 3 H]raclopride), dopamine D1([ 3 H]SCH23390), GABA A ([ 3 H]muscimol), benzodiazepine ([ 3 H]RO15-1788), and muscarinic ACh receptors ([ 3 H]QNB). [ 3 H]spiperone was elevated in striatal subregions only in haloperidol-treated rats, with the largest increases seen in the 8 month duration animals. Striatal [ 3 H]raclopride binding was increased after both short- and long-term treatment in both haloperidol and raclopride, but not clozapine-treated animals. Clozapine-treated rats showed significant increases in [ 3 H]SCH23390 in the nucleus accumbens after 28-day administration; otherwise no changes were seen for this ligand in any other groups. Increases in [ 3 H]muscimol binding in the substantia nigra reticulata were seen in haloperidol-treated rats after 8 month treatment. Binding of [ 3 H]QNB and [ 3 H]RO15-1788 were not significantly different from control for any of the drug-treated groups. These data suggest that persisting alterations in receptor binding are primarily seen in dopamine D2 and GABA receptors after withdrawal from chronic administration of haloperidol but not the atypical neuroleptics, clozapine and raclopride. (Authors)

  8. An application of a new planar positron imaging system (PPIS) in a small animal. MPTP-induced parkinsonism in mouse

    International Nuclear Information System (INIS)

    Takamatsu, Hiroyuki; Noda, Akihiro; Kakiuchi, Takeharu

    2004-01-01

    Recent animal PET research has led to the development of PET scanners for small animals. A planar positron imaging system (PPIS) was newly developed to study physiological function in small animals and plants in recent years. To examine the usefulness of PPIS for functional study in small animals, we examined dopaminergic images of mouse striata in MPTP-induced parkinsonism. Male C57BL/6NCrj mice were treated with MPTP 7 days before the PPIS study. Scans were performed to measure dopamine D 1 receptor binding and dopamine transporter availability with [ 11 C]SCH23390 (about 2 MBq) and [ 11 C]β-CFT (about 2 MBq), respectively. After the PPIS study, dopamine content in the striatum was measured by high-performance liquid chromatography (HPLC). The MPTP treatment significantly reduced dopamine content in the striatum 7 days after treatment. In the MPTP-treated group, [ 11 C]β-CFT binding in the striatum was significantly decreased compared with the control group, while striatal [ 11 C]SCH23390 binding was not affected. Dopamine content in the striatum was significantly correlated with the striatal binding of [ 11 C]β-CFT. The present results suggest that PPIS is able to determine brain function in a small animal. Using PPIS, high throughput imaging of small animal brain functions could be achieved. (author)

  9. Frontal-subcortical circuits in obsessive-compulsive disorder: role of the dopamine D1 receptor

    International Nuclear Information System (INIS)

    Olver, J.S.; Reutens, D.C.; Maruff, P.; Burrows, G.D.; Norman, T.R.; Ellen, S.R.; Pantelis, C.; Tochon-Danguy, H.; Ackermann, U.; Stekelenberg, N.

    2000-01-01

    Full text: Obsessive-Compulsive Disorder (OCD) is an anxiety disorder which is increasingly being recognised as a neurobiological disorder. While serotonergic mechanisms have been proposed, the major competing theory in the pathophysiology of OCD involves the neurotransmitter dopamine. The Dopamine D1 receptor is implicated in OCD following the finding of specific spatial working memory abnormalities in a series of neuropsychological studies. Spatial working memory is known to depend on the integrity of D1 receptor function in the Dorso-lateral Prefrontal Cortex (DLPFC) of primates. This study aims to examine the role of dopamine in patients with OCD and in particular to test the hypothesis that there is an upregulation of dopamine D1 receptors in the DLPFC which correlates with spatial working memory deficits in OCD. Three OCD patients and three normal controls underwent Positron Emission Tomography (PET) following intravenous injection of the D1 antagonist PET ligand SCH23390. Reconstructed PET images were co registered with subject Magnetic Resonance Images (MRI) and regions of interest drawn manually. We will present the analysis of the Binding Potentials of SCH23390 in the regions of interest of the first three OCD patients and compare them with three normal control patients. In conclusion Dopamine-Serotonergic interactions are involved in the pathophysiology of OCD. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  10. Die Universitätsbibliothek für Schüler - Angebote der UB Würzburg

    OpenAIRE

    Hämmer, Viola; Südekum, Karl

    2011-01-01

    Mit Einführungsveranstaltungen für Schüler, individueller Beratung bei der Recherche und einem eigenen Bereich auf der Homepage unterstützt die Universitätsbibliothek Würzburg Schüler bei ihren ersten wissenschaftlichen Arbeiten. Damit soll auch eine Brücke geschlagen werden zwischen den Bildungsinstitutionen Schule und Hochschule.

  11. Dopamine antagonists and brief vision distinguish lens-induced- and form-deprivation-induced myopia

    OpenAIRE

    Nickla, Debora L.; Totonelly, Kristen

    2011-01-01

    In eyes wearing negative lenses, the D2 dopamine antagonist spiperone was only partly effective in preventing the ameliorative effects of brief periods of vision (Nickla et al., 2010), in contrast to reports from studies using form deprivation. The present study was done to directly compare the effects of spiperone, and the D1 antagonist SCH-23390, on the two different myopiagenic paradigms. 12-day old chickens wore monocular diffusers (form deprivation) or − 10 D lenses attached to the feath...

  12. The Synergistic Roles of Cholecystokinin B and Dopamine D5 Receptors on the Regulation of Renal Sodium Excretion.

    Directory of Open Access Journals (Sweden)

    Xiaoliang Jiang

    Full Text Available Renal dopamine D1-like receptors (D1R and D5R and the gastrin receptor (CCKBR are involved in the maintenance of sodium homeostasis. The D1R has been found to interact synergistically with CCKBR in renal proximal tubule (RPT cells to promote natriuresis and diuresis. D5R, which has a higher affinity for dopamine than D1R, has some constitutive activity. Hence, we sought to investigate the interaction between D5R and CCKBR in the regulation of renal sodium excretion. In present study, we found D5R and CCKBR increase each other's expression in a concentration- and time-dependent manner in the HK-2 cell, the specificity of which was verified in HEK293 cells heterologously expressing both human D5R and CCKBR and in RPT cells from a male normotensive human. The specificity of D5R in the D5R and CCKBR interaction was verified further using a selective D5R antagonist, LE-PM436. Also, D5R and CCKBR colocalize and co-immunoprecipitate in BALB/c mouse RPTs and human RPT cells. CCKBR protein expression in plasma membrane-enriched fractions of renal cortex (PMFs is greater in D5R-/- mice than D5R+/+ littermates and D5R protein expression in PMFs is also greater in CCKBR-/- mice than CCKBR+/+ littermates. High salt diet, relative to normal salt diet, increased the expression of CCKBR and D5R proteins in PMFs. Disruption of CCKBR in mice caused hypertension and decreased sodium excretion. The natriuresis in salt-loaded BALB/c mice was decreased by YF476, a CCKBR antagonist and Sch23390, a D1R/D5R antagonist. Furthermore, the natriuresis caused by gastrin was blocked by Sch23390 while the natriuresis caused by fenoldopam, a D1R/D5R agonist, was blocked by YF476. Taken together, our findings indicate that CCKBR and D5R synergistically interact in the kidney, which may contribute to the maintenance of normal sodium balance following an increase in sodium intake.

  13. The yeast protein kinase Sch9 adjusts V-ATPase assembly/disassembly to control pH homeostasis and longevity in response to glucose availability.

    Directory of Open Access Journals (Sweden)

    Tobias Wilms

    2017-06-01

    Full Text Available The conserved protein kinase Sch9 is a central player in the nutrient-induced signaling network in yeast, although only few of its direct substrates are known. We now provide evidence that Sch9 controls the vacuolar proton pump (V-ATPase to maintain cellular pH homeostasis and ageing. A synthetic sick phenotype arises when deletion of SCH9 is combined with a dysfunctional V-ATPase, and the lack of Sch9 has a significant impact on cytosolic pH (pHc homeostasis. Sch9 physically interacts with, and influences glucose-dependent assembly/disassembly of the V-ATPase, thereby integrating input from TORC1. Moreover, we show that the role of Sch9 in regulating ageing is tightly connected with V-ATPase activity and vacuolar acidity. As both Sch9 and the V-ATPase are highly conserved in higher eukaryotes, it will be interesting to further clarify their cooperative action on the cellular processes that influence growth and ageing.

  14. Henoch-Schönlein purpura in an older man presenting as rectal bleeding and IgA mesangioproliferative glomerulonephritis: a case report.

    Science.gov (United States)

    Cheungpasitporn, Wisit; Jirajariyavej, Teeranun; Howarth, Charles B; Rosen, Raquel M

    2011-08-10

    Henoch-Schönlein purpura is the most common systemic vasculitis in children. Typical presentations are palpable purpura, abdominal pain, arthritis, and hematuria. This vasculitic syndrome can present as an uncommon cause of rectal bleeding in older patients. We report a case of an older man with Henoch-Schönlein purpura. He presented with rectal bleeding and acute kidney injury secondary to IgA mesangioproliferative glomerulonephritis. A 75-year-old Polish man with a history of diverticulosis presented with a five-day history of rectal bleeding. He had first noticed colicky left lower abdominal pain two months previously. At that time he was treated with a 10-day course of ciprofloxacin and metronidazole for possible diverticulitis. He subsequently presented with rectal bleeding to our emergency department. Physical examination revealed generalized palpable purpuric rash and tenderness on his left lower abdomen. Laboratory testing showed a mildly elevated serum creatinine of 1.3. Computed tomography of his abdomen revealed a diffusely edematous and thickened sigmoid colon. Flexible sigmoidoscopy showed severe petechiae throughout the colon. Colonic biopsy showed small vessel acute inflammation. Skin biopsy resulted in a diagnosis of leukocytoclastic vasculitis. Due to worsening kidney function, microscopic hematuria and new onset proteinuria, he underwent a kidney biopsy which demonstrated IgA mesangioproliferative glomerulonephritis. A diagnosis of Henoch-Schönlein purpura was made. Intravenous methylprednisolone was initially started and transitioned to prednisone tapering orally to complete six months of therapy. There was marked improvement of abdominal pain. Skin lesions gradually faded and gastrointestinal bleeding stopped. Acute kidney injury also improved. Henoch-Schönlein purpura, an uncommon vasculitic syndrome in older patients, can present with lower gastrointestinal bleeding, extensive skin lesions and renal involvement which responds well to

  15. Schéma équivalent petit signal d\\'un transistor à effet de champ à ...

    African Journals Online (AJOL)

    Dans cet article, les auteurs présentent un schéma équivalent petit signal d\\'un transistor à effet de champ à base de nano tube de carbone (CNTFETs). Les éléments du schéma équivalent sont obtenus à partir de la mesure des paramètres « scattering » S du CNTFETs pour un point de polarisation dans une gamme de ...

  16. Effect of Thyroxin Treatment on Carotid Intima-Media Thickness (CIMT) Reduction in Patients with Subclinical Hypothyroidism (SCH): a Meta-Analysis of Clinical Trials.

    Science.gov (United States)

    Aziz, Muhammad; Kandimalla, Yugandhar; Machavarapu, Archana; Saxena, Anshul; Das, Sankalp; Younus, Adnan; Nguyen, Michelle; Malik, Rehan; Anugula, Dixitha; Latif, Muhammad A; Humayun, Choudhry; Khan, Idrees M; Adus, Ali; Rasool, Aisha; Veledar, Emir; Nasir, Khurram

    2017-07-01

    Research shows that subclinical hypothyroidism (SCH) is related to an increased carotid intima-media thickness (CIMT), a surrogate marker of subclinical cardiovascular disease (CVD). It is controversial whether or not SCH should be treated to reduce CVD morbidity and mortality. This meta-analysis aimed to determine whether SCH is associated with an increase in CIMT as compared to Euthyroidism (EU) and whether thyroxin (T4) treatment in SCH can reverse the change in CIMT. Two independent reviewers conducted an extensive database research up to December 2016. A total of 12 clinical trials discussed the effect of Thyroxin on CIMT values at pre- and post-treatment in subjects with SCH. CIMT was significantly higher among SCH (n=280) as compared to EU controls (n=263) at baseline; the pooled weighted mean difference (WMD) of CIMT was 0.44 mm [95% confidence interval (CI) 0.14, 0.74], p=0.004; I 2 =65%. After treatment with thyroxin in subjects with SCH (n=314), there was a statistically significant decrease in CIMT from pre- to post-treatment; the pooled WMD of CIMT decrease was [WMD -0.32; 95% CI (-0.47, -0.16), p=<0.0001; I 2 =2%], and it was no longer different from EU controls [WMD 0.13 mm; 95% CI (-0.04, 0.30); p=0.14; I 2 =27%]. The total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) were higher in SCH as compared to EU controls and decreased significantly after treatment with thyroxin. This meta-analysis shows that thyroxin therapy in subjects with SCH significantly decreases CIMT and improves lipid profile, modifiable CVD risk factors. Thyroid hormone replacement in subjects with SCH may play a role in slowing down or preventing the progression of atherosclerosis.

  17. Autoradiographic analysis of regional alterations in brain receptors following chronic administration and withdrawal of typical and atypical neuroleptics in rats

    Energy Technology Data Exchange (ETDEWEB)

    See, R E; Ellison, G; Toga, A W [California Univ., Los Angeles, CA (USA). School of Medicine

    1990-01-01

    Rats were administered haloperidol, clozapine, raclopride, or no drug for 28 days or 8 months. Following a 3 week withdrawal period, in vitro autoradiography was utilized to examine receptor binding for dopamine D2(({sup 3}H)spiperone and ({sup 3}H)raclopride), dopamine D1(({sup 3}H)SCH23390), GABA{sub A}(({sup 3}H)muscimol), benzodiazepine (({sup 3}H)RO15-1788), and muscarinic ACh receptors (({sup 3}H)QNB). ({sup 3}H)spiperone was elevated in striatal subregions only in haloperidol-treated rats, with the largest increases seen in the 8 month duration animals. Striatal ({sup 3}H)raclopride binding was increased after both short- and long-term treatment in both haloperidol and raclopride, but not clozapine-treated animals. Clozapine-treated rats showed significant increases in ({sup 3}H)SCH23390 in the nucleus accumbens after 28-day administration; otherwise no changes were seen for this ligand in any other groups. Increases in ({sup 3}H)muscimol binding in the substantia nigra reticulata were seen in haloperidol-treated rats after 8 month treatment. Binding of ({sup 3}H)QNB and ({sup 3}H)RO15-1788 were not significantly different from control for any of the drug-treated groups. These data suggest that persisting alterations in receptor binding are primarily seen in dopamine D2 and GABA receptors after withdrawal from chronic administration of haloperidol but not the atypical neuroleptics, clozapine and raclopride. (Authors).

  18. Accelerated habit formation following amphetamine exposure is reversed by D1, but enhanced by D2, receptor antagonists

    Directory of Open Access Journals (Sweden)

    Andrew John Dudley Nelson

    2013-05-01

    Full Text Available Repeated exposure to the psychostimulant amphetamine has been shown to disrupt goal-directed instrumental actions and promote the early and abnormal development of goal-insensitive habitual responding (Nelson and Killcross, 2006. To investigate the neuropharmacological specificity of this effect as well as restore goal-directed responding in animals with pre-training amphetamine exposure, animals were treated with the non-selective dopamine antagonist α-flupenthixol, the selective D1 antagonist SCH 23390 or the selective D2 antagonist eticlopride, prior to instrumental training (3 sessions. Subsequently, the reinforcer was paired with LiCL-induced gastric-malaise and animals were given a test of goal-sensitivity both in extinction and reacquisition. The effect of these dopaminergic antagonists on the sensitivity of lever press performance to outcome devaluation was assessed in animals with pre-training exposure to amphetamine (Experiments 1a-1c or in non-sensitized animals (Experiment 2. Both α-flupenthixol and SCH23390 reversed accelerated habit formation following amphetamine sensitization. However, eticlopride appeared to enhance this effect and render instrumental performance compulsive as these animals were unable to inhibit responding both in extinction and reacquisition, even though a consumption test confirmed they had acquired an aversion to the reinforcer. These findings demonstrate that amphetamine induced-disruption of goal-directed behaviour is mediated by activity at distinct dopamine receptor subtypes and may represent a putative model of the neurochemical processes involved in the loss of voluntary control over behaviour.

  19. Systemic treatment with D-fenfluramine, but not sibutramine, blocks cue-induced reinstatement of food-seeking behavior in the rat.

    Science.gov (United States)

    Pratt, Wayne E; Ford, Ryan T

    2013-11-27

    Individuals struggling with obesity often have difficulty maintaining dietary regimens. One source of dietary relapse is the reinstatement of previous feeding behaviors following the presentation of cues indicating the availability of palatable but highly caloric food reward. The drugs fenfluramine and sibutramine have previously been prescribed because they enhance satiety mechanisms and decrease meal size. However, it is unclear whether these anorectic agents are also effective in blocking the cue-induced reinstatement of food-seeking behaviors. In these three experiments, we compared the effects of systemic treatment of d-fenfluramine (3mg/kg; N=10) and sibutramine (3mg/kg; N=11) with that of the D1 antagonist SCH 23390 (6μg/kg; N=11) at a dose that has previously been shown to attenuate cue-induced reinstatement. d-Fenfluramine treatment blocked the cue's ability to reinstate lever pressing as compared to the saline injection day. In contrast, sibutramine had no effect on cue-induced reinstatement; all animals reinstated their lever pressing during the first reinstatement test, and this was unaffected by sibutramine treatment. SCH 23390 treatment did not significantly reduce cue-induced reinstatement in this set of experiments. The results suggest that the motivational effects of d-fenfluramine is not limited to the promotion of satiety once a meal has been initiated, and demonstrate that some anorectic treatments may inhibit the effectiveness of conditioned cues to elicit relapse of food-seeking behavior. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. Dopamine D1 receptor activation maintains motor coordination in injured rats but does not accelerate the recovery of the motor coordination deficit.

    Science.gov (United States)

    Avila-Luna, Alberto; Gálvez-Rosas, Arturo; Alfaro-Rodríguez, Alfonso; Reyes-Legorreta, Celia; Garza-Montaño, Paloma; González-Piña, Rigoberto; Bueno-Nava, Antonio

    2018-01-15

    The sensorimotor cortex and the striatum are interconnected by the corticostriatal pathway, suggesting that cortical injury alters the striatal function that is associated with skilled movements and motor learning, which are functions that may be modulated by dopamine (DA). In this study, we explored motor coordination and balance in order to investigate whether the activation of D 1 receptors (D 1 Rs) modulates functional recovery after cortical injury. The results of the beam-walking test showed motor deficit in the injured group at 24, 48 and 96h post-injury, and the recovery time was observed at 192h after cortical injury. In the sham and injured rats, systemic administration of the D 1 R antagonist SCH-23390 (1mg/kg) alone at 24, 48, 96 and 192h significantly (Pmotor deficit, while administration of the D 1 R agonist SKF-38393 alone (2, 3 and 4mg/kg) at 24, 48, 96 and 192h post-injury did not produce a significant difference; however, the co-administration of SKF-38393 and SCH-23390 prevented the antagonist-induced increase in the motor deficit. The cortical+striatal injury showed significantly increased the motor deficit at 24, 48, 96 and 192h post-injury (Pmotor recovery, but the activation of D 1 Rs maintained motor coordination, confirming that an intact striatum may be necessary for achieving recovery. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Prevalence and Characteristics of Nonblanching, Palpable Skin Lesions With a Linear Pattern in Children With Henoch-Schönlein Syndrome.

    Science.gov (United States)

    Milani, Gregorio P; Lava, Sebastiano A G; Ramelli, Vera; Bianchetti, Mario G

    2017-11-01

    Linear nonblanching skin lesions are thought to occur very rarely in patients with Henoch-Schönlein syndrome. To examine the prevalence and characteristics of linear nonblanching skin lesions in children with Henoch-Schönlein syndrome. A prospective case series was conducted at the ambulatory practice of a hospitalist between January 1, 2010, and December 31, 2015, among 31 consecutive children with Henoch-Schönlein syndrome. Thirty-one consecutive children affected with Henoch-Schönlein syndrome who were from 3.0 to 12.0 years of age (median age, 6.2 years). Children with Henoch-Schönlein syndrome underwent a careful, structured skin examination established in advance with emphasis on the presence of palpable lesions with a linear pattern. Among the 31 children in the study (12 girls and 19 boys; median age, 6.2 years [range, 3.0-12.0 years]), 8 (26%) had linear lesions on the legs, groin, waistline, wrists, or forearms. Patients with or without linear lesions did not differ significantly with respect to sex, age, and cutaneous, abdominal, articular, or renal involvement. This study illustrates the prevalence and characteristics of linear skin lesions in patients with Henoch-Schönlein syndrome. Patients with symptoms suggestive of this vasculitis should be evaluated for the presence of nonblanching, palpable lesions with a linear pattern.

  2. Effects of anesthesia and species on the uptake or binding of radioligands in vivo in the Göttingen minipig

    DEFF Research Database (Denmark)

    Alstrup, Aage Kristian Olsen; Landau, Anne M.; Holden, James E.

    2013-01-01

    Progress in neuroscience research often involves animals, as no adequate alternatives exist to animal models of living systems. However, both the physiological characteristics of the species used and the effects of anesthesia raise questions of common concern. Here, we demonstrate the confounding...... influences of these effects on tracer binding in positron emission tomography (PET). We determined the effects of two routinely used anesthetics (isoflurane and propofol) on the binding of two tracers of monoamine function, [ C 11 ]SCH23390, a tracer of the dopamine D1 and D5 receptors, and the alpha2...

  3. Henoch-Schönlein purpura in an older man presenting as rectal bleeding and IgA mesangioproliferative glomerulonephritis: a case report

    Directory of Open Access Journals (Sweden)

    Howarth Charles B

    2011-08-01

    Full Text Available Abstract Introduction Henoch-Schönlein purpura is the most common systemic vasculitis in children. Typical presentations are palpable purpura, abdominal pain, arthritis, and hematuria. This vasculitic syndrome can present as an uncommon cause of rectal bleeding in older patients. We report a case of an older man with Henoch-Schönlein purpura. He presented with rectal bleeding and acute kidney injury secondary to IgA mesangioproliferative glomerulonephritis. Case presentation A 75-year-old Polish man with a history of diverticulosis presented with a five-day history of rectal bleeding. He had first noticed colicky left lower abdominal pain two months previously. At that time he was treated with a 10-day course of ciprofloxacin and metronidazole for possible diverticulitis. He subsequently presented with rectal bleeding to our emergency department. Physical examination revealed generalized palpable purpuric rash and tenderness on his left lower abdomen. Laboratory testing showed a mildly elevated serum creatinine of 1.3. Computed tomography of his abdomen revealed a diffusely edematous and thickened sigmoid colon. Flexible sigmoidoscopy showed severe petechiae throughout the colon. Colonic biopsy showed small vessel acute inflammation. Skin biopsy resulted in a diagnosis of leukocytoclastic vasculitis. Due to worsening kidney function, microscopic hematuria and new onset proteinuria, he underwent a kidney biopsy which demonstrated IgA mesangioproliferative glomerulonephritis. A diagnosis of Henoch-Schönlein purpura was made. Intravenous methylprednisolone was initially started and transitioned to prednisone tapering orally to complete six months of therapy. There was marked improvement of abdominal pain. Skin lesions gradually faded and gastrointestinal bleeding stopped. Acute kidney injury also improved. Conclusion Henoch-Schönlein purpura, an uncommon vasculitic syndrome in older patients, can present with lower gastrointestinal bleeding

  4. Chomsky-Schützenberger parsing for weighted multiple context-free languages

    Directory of Open Access Journals (Sweden)

    Tobias Denkinger

    2017-07-01

    Full Text Available We prove a Chomsky-Schützenberger representation theorem for multiple context-free languages weighted over complete commutative strong bimonoids. Using this representation we devise a parsing algorithm for a restricted form of those devices.

  5. Interplay among Gcn5, Sch9 and mitochondria during chronological aging of wine yeast is dependent on growth conditions.

    Directory of Open Access Journals (Sweden)

    Cecilia Picazo

    Full Text Available Saccharomyces cerevisiae chronological life span (CLS is determined by a wide variety of environmental and genetic factors. Nutrient limitation without malnutrition, i.e. dietary restriction, expands CLS through the control of nutrient signaling pathways, of which TOR/Sch9 has proven to be the most relevant, particularly under nitrogen deprivation. The use of prototrophic wine yeast allows a better understanding of the role of nitrogen in longevity in natural and more demanding environments, such as grape juice fermentation. We previously showed that acetyltransferase Gcn5, a member of the SAGA complex, has opposite effects on CLS under laboratory and winemaking conditions, and is detrimental under the latter. Here we demonstrate that integrity of the SAGA complex is necessary for prolonged longevity, as its dismantling by SPT20 deletion causes a drop in CLS under both laboratory and winemaking conditions. The sch9Δ mutant is long-lived in synthetic SC medium, as expected, and the combined deletion of GCN5 partially suppresses this phenotype. However it is short-lived in grape juice, likely due to its low nitrogen/carbon ratio. Therefore, unbalance of nutrients can be more relevant for life span than total amounts of them. Deletion of RTG2, which codes for a protein associated with Gcn5 and is a component of the mitochondrial retrograde signal, and which communicates mitochondrial dysfunction to the nucleus, is detrimental under laboratory, but not under winemaking conditions, where respiration seems not so relevant for longevity. Transcription factor Rgm1 was found to be a novel CLS regulator Sch9-dependently.

  6. N-methylisatin-beta-thiosemicarbazone derivative (SCH 16 is an inhibitor of Japanese encephalitis virus infection in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Sriram D

    2008-05-01

    Full Text Available Abstract Background During the early and mid part of 20th century, several reports described the therapeutic effects of N-methylisatin-β-Thiosemicarbazone (MIBT against pox viruses, Maloney leukemia viruses and recently against HIV. However, their ability to inhibit flavivirus replication has not been investigated. Hence the present study was designed to evaluate the antiviral activity of 14 MIBT derivatives against Flaviviruses that are prevalent in India such as Japanese Encephalitis Virus (JEV, Dengue-2 (Den-2 and West Nile viruses (WNV. Results Amongst the fourteen Mannich bases of MIBT derivatives tested one compound – SCH 16 was able to completely inhibit in vitro Japanese encephalitis virus (JEV and West Nile virus (WNV replication. However no antiviral activity of SCH 16 was noted against Den-2 virus replication. This compound was able to inhibit 50% of the plaques (IC50 produced by JEV and WNV at a concentration of 16 μgm/ml (0.000025 μM and 4 μgm/ml (0.000006 μM respectively. Furthermore, SCH 16 at a concentration of 500 mg/kg body weight administered by oral route twice daily was able to completely (100% prevent mortality in mice challenged with 50LD50 JEV by the peripheral route. Our experiments to understand the mechanism of action suggest that SCH 16 inhibited JEV replication at the level of early protein translation. Conclusion Only one of the 14 isatin derivatives -SCH 16 exhibited antiviral action on JEV and WNV virus infection in vitro. SCH 16 was also found to completely inhibit JEV replication in vivo in a mouse model challenged peripherally with 50LD50 of the virus. These results warrant further research and development on SCH 16 as a possible therapeutic agent.

  7. Federal Act on Protection against Nuisances (BImSchG) and supplementing regulations. 11. ed.

    International Nuclear Information System (INIS)

    Hansmann, K.

    1993-01-01

    This handy booklet contains the BImSchG and related implementing regulations as well as the Technical Codes Clean Air and Noise Abatement. The contribution on the BImSchG explains the origin of the Act, the scope of application, its concept and principles. The contents of the Act is portrayed by emphasizing subject-related connections. Dealt with are also regulations for installations requiring licensing, the measurement of airborne pollution, stipulations concerning the area of installations and transport, as well as the regulation concerning the monitoring of airborne pollution in the Federal Republic of Germany. (orig.) [de

  8. Federal Act on Protection against Nuisances (BImSchG) and supplementing regulations. 9. ed.

    International Nuclear Information System (INIS)

    Hansmann, K.

    1992-01-01

    This handy booklet contains the BImSchG and related implementing regulations as well as the Technical Codes Clean Air and Noise Abatement. The contribution on the BImSchG explains the origin of the Act, the scope of application, its concept and principles. The contents of the Act is portrayed by emphasizing subject-related connections. Dealt with are also regulations for installations requiring licensing, the measurement of airborne pollution, stipulations concerning the area of installations and transport, as well as the regulation concerning the monitoring of airborne pollution in the Federal Republic of Germany. (orig.) [de

  9. Lipid Signaling via Pkh1/2 Regulates Fungal CO2 Sensing through the Kinase Sch9.

    Science.gov (United States)

    Pohlers, Susann; Martin, Ronny; Krüger, Thomas; Hellwig, Daniela; Hänel, Frank; Kniemeyer, Olaf; Saluz, Hans Peter; Van Dijck, Patrick; Ernst, Joachim F; Brakhage, Axel; Mühlschlegel, Fritz A; Kurzai, Oliver

    2017-01-31

    Adaptation to alternating CO 2 concentrations is crucial for all organisms. Carbonic anhydrases-metalloenzymes that have been found in all domains of life-enable fixation of scarce CO 2 by accelerating its conversion to bicarbonate and ensure maintenance of cellular metabolism. In fungi and other eukaryotes, the carbonic anhydrase Nce103 has been shown to be essential for growth in air (~0.04% CO 2 ). Expression of NCE103 is regulated in response to CO 2 availability. In Saccharomyces cerevisiae, NCE103 is activated by the transcription factor ScCst6, and in Candida albicans and Candida glabrata, it is activated by its homologues CaRca1 and CgRca1, respectively. To identify the kinase controlling Cst6/Rca1, we screened an S. cerevisiae kinase/phosphatase mutant library for the ability to regulate NCE103 in a CO 2 -dependent manner. We identified ScSch9 as a potential ScCst6-specific kinase, as the sch9Δ mutant strain showed deregulated NCE103 expression on the RNA and protein levels. Immunoprecipitation revealed the binding capabilities of both proteins, and detection of ScCst6 phosphorylation by ScSch9 in vitro confirmed Sch9 as the Cst6 kinase. We could show that CO 2 -dependent activation of Sch9, which is part of a kinase cascade, is mediated by lipid/Pkh1/2 signaling but not TORC1. Finally, we tested conservation of the identified regulatory cascade in the pathogenic yeast species C. albicans and C. glabrata Deletion of SCH9 homologues of both species impaired CO 2 -dependent regulation of NCE103 expression, which indicates a conservation of the CO 2 adaptation mechanism among yeasts. Thus, Sch9 is a Cst6/Rca1 kinase that links CO 2 adaptation to lipid signaling via Pkh1/2 in fungi. All living organisms have to cope with alternating CO 2 concentrations as CO 2 levels range from very low in the atmosphere (0.04%) to high (5% and more) in other niches, including the human body. In fungi, CO 2 is sensed via two pathways. The first regulates virulence in

  10. Conhecimento tácito e conhecimento escolar na formação do professor (por que Donald Schön não entendeu Luria Tacit knowledge and school knowledge in teachers' education (why Donald Schön didn't understand Luria

    Directory of Open Access Journals (Sweden)

    Newton Duarte

    2003-08-01

    Full Text Available O objetivo do texto é mostrar que os estudos de Donald Schön no campo da formação profissional em geral e da formação de professores em particular pautam-se numa epistemologia que desvaloriza o conhecimento científico/teórico/acadêmico e numa pedagogia que desvaloriza o saber escolar. Nesta direção é feita uma análise crítica das idéias de Schön acerca do conhecimento tácito e do conhecimento escolar. Essa análise crítica das idéias de Schön é inserida no contexto de uma crítica aos pressupostos epistemológicos hegemônicos atualmente no campo dos estudos sobre formação de professores.This paper defends that Donald Schön's works on professional education in general and more particularly on teachers' education are based both on an epistemology that devalues scientific knowledge and on a pedagogy that devalues school knowledge. A critical analysis of Schön's concepts of tacit knowledge (or reflection-in-action and school knowledge is presented. This critical analysis is inserted in the context of a criticism of the currently hegemonic epistemological ideas in the field of studies on teachers' education.

  11. Intuition in medical practice: A reflection on Donald Schön's reflective practitioner.

    Science.gov (United States)

    Mickleborough, Tim

    2015-01-01

    In a recent commentary, Dr. Abhishek Biswas asks the question whether physicians should rely on their "gut feeling" when making clinical decisions. Biswas describes a situation where his intuition resulted in an immediate course of action that prompted urgent medical attention for a patient who had "routine" pain. Inspired by the author's account, I would like to further Biswas' discussion and examine its importance using the educational theories of Donald Schön and his concept of the reflective practitioner. Schön argues that technical knowledge alone is not sufficient to solve the complex problems that professionals face on a daily basis and intuition, developed through a reflective practice, is crucial for any professional's practice, especially in a time of greater uncertainty in the workplace.

  12. Non-thrombocytopenic purpura in familial Mediterranean fever-comorbidity with Henoch-Schönlein purpura or an additional rare manifestation of familial Mediterranean fever?

    Science.gov (United States)

    Ben-Chetrit, Eldad; Yazici, Hasan

    2016-07-01

    Henoch-Schönlein purpura is a relatively common vasculitis mainly affecting children. It is characterized by purpuric skin rash, abdominal cramping, and haematuria. Skin biopsies taken from Henoch-Schönlein purpura lesions disclose perivascular IgA deposits. FMF is an autoinflammatory disease characterized by recurrent attacks of fever lasting 2-3 days which resolve spontaneously. Typical manifestations of the disease are peritonitis, pleuritis, pericarditis, arthritis and erysipelas-like erythema usually affecting the lower limbs. Over the years many reviews emphasized the clinical impression that Henoch-Schönlein purpura is more common among FMF patients than in healthy control population. In this review we summarize these reports and show that sometimes Henoch-Schönlein purpura associated with FMF differs from typical isolated Henoch-Schönlein purpura, and this is also the case with polyarteritis nodosa and SpA associated with FMF. It is suggested that these clinical manifestations (polyarteritis nodosa, Henoch-Schönlein purpura and SpA) should be considered to be associated with FMF as part of what we call FMF rather than as co-existing additional separate clinical entities. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Yohimbine reinstates extinguished 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) seeking in rats with prior exposure to chronic yohimbine.

    Science.gov (United States)

    Ball, Kevin T; Jarsocrak, Hanna; Hyacinthe, Johanna; Lambert, Justina; Lockowitz, James; Schrock, Jordan

    2015-11-01

    Although exposure to acute stress has been shown to reinstate extinguished responding for a wide variety of drugs, no studies have investigated stress-induced reinstatement in animals with a history of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) self-administration. Thus, rats were trained to press a lever for MDMA (0.50 mg/kg/infusion) in daily sessions, and lever pressing was subsequently extinguished in the absence of MDMA and conditioned cues (light and tone). We then tested the ability of acute yohimbine (2.0 mg/kg), a pharmacological stressor, to reinstate lever-pressing under extinction conditions. Additionally, to model chronic stress, some rats were injected daily with yohimbine (5.0 mg/kg × 10 days) prior to reinstatement tests. To assess dopaminergic involvement, chronic yohimbine injections were combined with injections of SCH-23390 (0.0 or 10.0 μg/kg), a dopamine D1-like receptor antagonist. In a separate experiment, rats with a history of food self-administration were treated and tested in the same way. Results showed that acute yohimbine injections reinstated extinguished MDMA and food seeking, but only in rats with a history of chronic yohimbine exposure. Co-administration of SCH-23390 with chronic yohimbine injections prevented the potentiation of subsequent food seeking, but not MDMA seeking. These results suggest that abstinent MDMA users who also are exposed to chronic stress may be at increased risk for future relapse, and also that the effects of chronic stress on relapse may be mediated by different mechanisms depending on one's drug use history. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Sexual behavior modulates contextual fear memory through dopamine D1/D5 receptors.

    Science.gov (United States)

    Bai, Hua-Yi; Cao, Jun; Liu, Na; Xu, Lin; Luo, Jian-Hong

    2009-03-01

    Traumatic events always lead to aversive emotional memory, i.e., fear memory. In contrast, positive events in daily life such as sex experiences seem to reduce aversive memory after aversive events. Thus, we hypothesized that post-traumatic pleasurable experiences, especially instinctive behaviors such as sex, might modulate traumatic memory through a memory competition mechanism. Here, we first report that male rats persistently expressed much lower fear responses when exposed to females, but not when exposed to males, for 24 h immediately after contextual fear conditioning. Remarkably, this effect of sexual behavior was blocked by either systemic or intrahippocampal injection of the dopamine D1/D5 receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390) and was mimicked by systemic but not intrahippocampal injection of the D1/D5 receptor agonist R(+)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol hydrochloride (SKF39393). Furthermore, as a candidate mechanism underlying contextual fear memory, the impaired induction of hippocampal long-term potentiation (LTP) elicited by conditioned fear was rescued in male rats immediately exposed to female but not male rats for 24 h. Systemic injection of the dopamine D1/D5 receptor antagonist SCH23390 or agonist SKF38393 prevented or mimicked the effect of sexual behavior on the impaired induction of hippocampal LTP. Thus, our finding suggests that dopaminergic functions may, at least partially, govern competition between contextual fear and enjoyable memories through the modulation of hippocampal LTP.

  15. Increased dopamine D1 receptor binding in the human mesocortical system following central cholinergic activation

    International Nuclear Information System (INIS)

    Fedi, M.; Berkovic, S.F.; Tochon-Danguy, H.J.; Reutens, D.C.

    2002-01-01

    Full text: The interaction between the cholinergic and dopaminergic system has been implicated in many pathological processes including, Alzheimer's disease, schizophrenia and drug addiction. Little is known about the control of dopamine (DA) release following central cholinergic activation in humans, but experimental studies suggest that endogenously released Acetylcholine (ACh) achieved by the administration of cholinesterase inhibitors, can increase dopamine efflux in different regions of the brain. This leads to the activation of different types of post-synaptic dopaminergic receptors which belong to the family of G-protein coupled receptors (GPCRs). A common paradigm of the GPCRs desensitization is that agonist-induced receptor signaling is rapidly attenuated by receptor internalisation. Several experiments have shown that the activation of Dl receptors in acute conditions leads, within minutes, to translocation of the receptor from the surface of the neurons to the endosomal compartment in the cytoplasm and increased receptor turnover. To assess changes in Dl receptor density following an intravenous infusion of the selective cholinesterase inhibitor physostigmine salicylate (PHY), we studied eleven normal subjects (10 male and 1 female, mean age 36.1 and 61617; 9.9) using [11C]-SCH23390 and PET The binding potential (BP) for SCH23390 was significantly (p 0.05). There was no statistically significant difference between baseline and physostigmine Kl ratio (p>0.05) suggesting that BP changes observed were not secondary to regional blood flow changes or to an order effect of the scans. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  16. The effect of CA1 dopaminergic system on amnesia induced by harmane in mice.

    Science.gov (United States)

    Nasehi, Mohammad; Hasanvand, Simin; Khakpai, Fatemeh; Zarrindast, Mohammad-Reza

    2018-05-16

    In the present study, the effects of bilateral injections of dopaminergic drugs into the hippocampal CA1 regions (intra-CA1) on harmane-induced amnesia were examined in mice. We used a single-trial step-down inhibitory avoidance task for the assessment of memory acquisition in adult male mice. Our data indicated that pre-training intra-peritoneal (i.p.) administration of harmane (12 mg/kg) impaired memory acquisition. Moreover, intra-CA1 administration of dopamine D1 receptor agonist, SKF38393 (0.25 µg/mouse), dopamine D1 receptor antagonist, SCH23390 (0.25 µg/mouse), dopamine D2 receptor agonist, quinpirole (0.125 and 0.25 µg/mouse) and dopamine D2 receptor antagonist, sulpiride (0.2 and 0.4 µg/mouse) decreased the learning of a single-trial inhibitory avoidance task. Furthermore, pre-training intra-CA1 injection of sub-threshold doses of SKF38393 (0.0625 µg/mouse) or sulpiride (0.1 µg/mouse) increased pre-training harmane (4 and 8 mg/kg, i.p.)-induced amnesia. On the other hand, pre-training intra-CA1 injection of a sub-threshold dose of SCH23390 (0.0625 µg/mouse) reversed amnesia induced by an effective dose of harmane (12 mg/kg; i.p.). In addition, Pre-training intra-CA1 injection of quinpirole (0.0625 µg/mouse) had no effect on memory impairment induced by harmane. These findings indicate the involvement of CA1 dopaminergic system on harmane-induced impairment of memory acquisition.

  17. Association of endothelial nitric oxide synthase gene polymorphism with the risk of Henoch-Schönlein purpura/Henoch-Schönlein purpura nephritis.

    Science.gov (United States)

    Zhong, Weiqiang; Zhou, Tian-Biao; Jiang, Zongpei

    2015-04-01

    Association between endothelial nitric oxide synthase (eNOS) gene polymorphism and Henoch-Schönlein purpura (HSP)/Henoch-Schönlein purpura nephritis (HSPN) risk is still controversial. A meta-analysis was performed to evaluate the association between eNOS gene polymorphism and HSP/HSPN susceptibility. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic database. Three articles were identified for the analysis of association between eNOS gene polymorphism and HSPN/HSP risk. eNOS G894T gene polymorphism was not associated with HSPN susceptibility and the risk of patients with HSP developing into HSPN. Interestingly, eNOS G894T T allele and GG genotype were associated with HSP susceptibility, but not the TT genotype. eNOS T786C TT genotype was associated with HSPN susceptibility, but not C allele and CC genotype. Furthermore, eNOS T786C gene polymorphism was not associated with HSP risk and the risk of patients with HSP developing into HSPN. In conclusion, eNOS T786C TT genotype was associated with and eNOS G894T T allele and GG genotype were associated with HSP susceptibility. However, more studies should be performed in the future.

  18. Mädchenschule und Geschlecht: Eine fallrekonstruktive Untersuchung der kollektiven Orientierungen und Weiblichkeitskonstruktionen von Schülerinnen monoedukativer Schulen

    OpenAIRE

    Waburg, Wiebke

    2010-01-01

    Die Dissertation ist im Rahmen des Projektes "Schulkultur, Geschlechtersegregation und Mädchensozialisation – DIAM" (Projektleitung L. Herwartz-Emden; gefördert von der DFG) entstandenen. In der Arbeit erfolgt die Rekonstruktion der Geschlechtskonstruktionen von Schülerinnen aus Mädchenschulen. Untersucht werden die kollektiven (geschlechtsbezogenen) Orientierungen von Mädchen und jungen Frauen im Alter von 13-19 Jahren. Die Schülerinnen befinden sich in der kulturell definierten Altersphase ...

  19. Lasing characteristics of 1.5 μm GaInAsP-InP SCH-BIG-DR lasers

    International Nuclear Information System (INIS)

    Shim, J.I.; Komori, K.; Arai, S.; Arima, I.; Suematsu, Y.; Somchai, R.

    1991-01-01

    This paper reports that higher differential quantum efficiency η df , smaller chirp Δλ, narrower linewidth Δν, and high coupling efficiency C out between active and passive regions of 1.5 μm GaInAsP/In PSCH-BIG-Dr lasers with a thin active layer and asymmetric gratings are experimentally demonstrated by a comparison of those properties of DFB lasers from the same wafer. A submode suppression ratio (SMSR) of more than 39 dB at 1.7 times the threshold current and a C out of almost 100% in the SCH-BIG-DR lasers indicated that a separate-confinement-heterostructure (SCH) with a thin active layer and a bundle-integrated-guide (BIG) structure are quite adequate to realize high-performance distributed reflector (DR-type lasers) a two times larger η df and 16 times larger front-to-rear output ratio (FROR) of SCH-BIG-DR lasers that those of DFB lasers showed the superiority of DR lasers for high-efficiency operation. Furthermore, superior spectral characteristics of the SCH-BIG-DR laser in comparison to those of conventional DFB lasers, i.e., only about a half of chirping under a rapid direction modulation, as well as 1/5 of the linewidth-power product, were also obtained, which originated from the smaller effective linewidth enhancement factor α eff of the DR laser

  20. Tor1/Sch9-regulated carbon source substitution is as effective as calorie restriction in life span extension.

    Directory of Open Access Journals (Sweden)

    Min Wei

    2009-05-01

    Full Text Available The effect of calorie restriction (CR on life span extension, demonstrated in organisms ranging from yeast to mice, may involve the down-regulation of pathways, including Tor, Akt, and Ras. Here, we present data suggesting that yeast Tor1 and Sch9 (a homolog of the mammalian kinases Akt and S6K is a central component of a network that controls a common set of genes implicated in a metabolic switch from the TCA cycle and respiration to glycolysis and glycerol biosynthesis. During chronological survival, mutants lacking SCH9 depleted extracellular ethanol and reduced stored lipids, but synthesized and released glycerol. Deletion of the glycerol biosynthesis genes GPD1, GPD2, or RHR2, among the most up-regulated in long-lived sch9Delta, tor1Delta, and ras2Delta mutants, was sufficient to reverse chronological life span extension in sch9Delta mutants, suggesting that glycerol production, in addition to the regulation of stress resistance systems, optimizes life span extension. Glycerol, unlike glucose or ethanol, did not adversely affect the life span extension induced by calorie restriction or starvation, suggesting that carbon source substitution may represent an alternative to calorie restriction as a strategy to delay aging.

  1. Bundes-Immissionsschutzgesetz (Federal Nuisance Protection Act). BImSchG, BImSch-Verordnungen, EMASPrivilegV, Biokraft-NachV, TA Luft, TA Laerm, USchadG, TEHG, ZuG 2012, ZuV 2012, EHVV 2012, FlugISchG, 2. FlugLSV. 29. ed.; Bundes-Immissionsschutzgesetz. BImSchG, BImSch-Verordnungen, EMASPrivilegV, Biokraft-NachV, TA Luft, TA Laerm, USchadG, TEHG, ZuG 2012, ZuV 2012, EHVV 2012, FlugISchG, 2. FlugLSV

    Energy Technology Data Exchange (ETDEWEB)

    Hansmann, Klaus (ed.)

    2011-07-01

    After a detailed introduction, the book goes into detail about the specifications of the Federal Immission Control Act (BImSchG). Also discussed are all regulations for the implementation of the BImSchG, the EMAS-Privilegierungsverordnung (privileges ordinance), the biofuels sustainibility ordinance (Biokraft-NachV), the Technical Instructions on Air Quality Control (TA Luft) and the Technical Instructions on Noise Control (TA Laerm), the Environmental Damage Act (Umweltschadensgesetz), the Greenhouse Gas Emissions Act (Treibhausgas-Emissionshandelsgesetz), the Allocation Act (Zuteilungsgesetz 2012), the Allocation Ordinance (Zuteilungsverordnung 2012), the Auctioning Ordinance (Emissionshandels-Versteigerungsverordnung 2012), and the Aircraft Noise Act (Gesetz zum Schutz gegen Fluglaerm) and the Ordinance on Noise Protection in Airports (Flugplatz-Schallschutzmassnahmenverordnung).

  2. Protein kinase FgSch9 serves as a mediator of the target of rapamycin and high osmolarity glycerol pathways and regulates multiple stress responses and secondary metabolism in Fusarium graminearum.

    Science.gov (United States)

    Gu, Qin; Zhang, Chengqi; Yu, Fangwei; Yin, Yanni; Shim, Won-Bo; Ma, Zhonghua

    2015-08-01

    Saccharomyces cerevisiae protein kinase Sch9 is one of the downstream effectors of the target of rapamycin (TOR) complex 1 and plays multiple roles in stress resistance, longevity and nutrient sensing. However, the functions of Sch9 orthologs in filamentous fungi, particularly in pathogenic species, have not been characterized to date. Here, we investigated biological and genetic functions of FgSch9 in Fusarium graminearum. The FgSCH9 deletion mutant (ΔFgSch9) was defective in aerial hyphal growth, hyphal branching and conidial germination. The mutant exhibited increased sensitivity to osmotic and oxidative stresses, cell wall-damaging agents, and to rapamycin, while showing increased thermal tolerance. We identified FgMaf1 as one of the FgSch9-interacting proteins that plays an important role in regulating mycotoxin biosynthesis and virulence of F. graminearum. Co-immunoprecipitation and affinity capture-mass spectrometry assays showed that FgSch9 also interacts with FgTor and FgHog1. More importantly, both ΔFgSch9 and FgHog1 null mutant (ΔFgHog1) exhibited increased sensitivity to osmotic and oxidative stresses. This defect was more severe in the FgSch9/FgHog1 double mutant. Taken together, we propose that FgSch9 serves as a mediator of the TOR and high osmolarity glycerol pathways, and regulates vegetative differentiation, multiple stress responses and secondary metabolism in F. graminearum. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

  3. Atmospheric chemistry of dimethyl sulfide. Kinetics of the CH3SCH2O2 + NO2 reaction in the gas phase at 296 K

    DEFF Research Database (Denmark)

    Nielsen, O.J.; Sehested, J.; Wallington, T.J.

    1995-01-01

    The pulse radiolysis of SF6/CH3SCH3/O-2/NO2 gas mixtures was used to generate CH3SCH2O2 radicals in the presence of NO2. By monitoring the rate of NO2 decay using its absorption at 400 nm, rate constants for the reaction of CH3SCH2O2 radicals with NO2 were measured to be (9.2 +/- 0.9) x 10...

  4. Cuidar em oncologia na perspectiva de Alfred Schütz Cuidado en oncología segundo Alfred Schütz Oncological care according Alfred Schütz

    Directory of Open Access Journals (Sweden)

    Regina Célia Popim

    2005-10-01

    Full Text Available O estudo foi realizado com enfermeiros oncológicos em seu cotidiano de trabalho. O objetivo foi compreender a ação subjetiva desses profissionais a partir de sua relação enfermeiro-doente. O referencial fenomenológico, fundamentado nas idéias de Alfred Schütz, possibilitou essa compreensão. Diante de uma questão orientadora: o que significa para você cuidar em oncologia? descreva para mim, foram obtidos depoimentos, os quais, depois de analisados, permitiram chegar ao típico da ação do cuidador enfermeiro neste cotidiano. O estudo revelou que cuidar em oncologia implica em lidar com o humano em situação de fragilidade; requer uma relação de afetividade; é um cuidado que traz consigo a gênese do desgaste profissional. O cuidado em oncologia reveste-se de grande complexidade, requerendo do profissional uma competência que vai para além da esfera técnico-científica. Nesse sentido, o enfermeiro necessita buscar por estratégias que lhe possibilitem o enfrentamento do desgaste a que é submetido em seu trabalho.El estudio fue realizado con enfermeros oncológicos en su cotidiano de trabajo. El objetivo fue comprender la acción subjetiva de esos profesionales desde la relación enfermero-enfermo. El referencial fenomenológico, fundamentado en las ideas de Alfred Schütz, posibilitó esa comprensión. Delante de una cuestión orientadora: ¿qué significa para usted el cuidado en oncología? Descríbame, se obtuvo declaraciones que, tras análisis, permitieron llegar a lo que es típico en la acción cotidiana del cuidador enfermero. El estudio reveló que cuidar en oncología implica tratar con el ser humano en situación de fragilidad; requiere una relación de afectividad; es un cuidado que trae consigo la génesis del desgaste profesional. El cuidado en oncología se reviste de gran complejidad y requiere del profesional una competencia que va más allá de la esfera técnico-científica. En ese sentido, el enfermero

  5. Heinrich Schütz as European cultural agent at the Danish courts

    DEFF Research Database (Denmark)

    Moe, Bjarke

    2011-01-01

    that Schütz in his Danish engagement was far more than an esteemed composer. As cultural agent with contacts throughout Europe he played an important role in providing the Danish courts with desirable musicians and music. While staying in the Danish capital he extended his European network in a way so that he......Based on recent studies of sources linked to the musical milieus at the Danish courts, this article argues that Heinrich Schütz acted as European cultural agent in musical affairs while staying in Copenhagen. As Kapelmester at the Danish Court (1633-35 and 1642-44) he built up the chapel...... by engaging musicians from his own circles, e.g. members of the Saxon Hofkapelle as well as members of his own family. Both Danish Courts, the King's and the Prince-elect's, enjoyed his contacts with several European musical centres, from where he among other things purchased new music. The paper shows...

  6. Craniota, Wirbel- oder Schädeltiere

    Science.gov (United States)

    Schultze, Hans-Peter

    Zu den Craniota zählen alle Chordatiere, die eine dreiteilige Regionalisierung des Körpers in Kopf, Rumpf und Schwanz aufweisen. Der Kopf umfasst (1) das Neurocranium mit Gehirn und komplexen Sinnesorganen zur Wahrnehmung der Umgebung, (2) das Viscerocranium zur Nahrungsaufnahme und zur Ventilation der Kiemen bei den primär wasserlebenden Craniota und (3) das Dermatocranium (S. 38). Letzteres entsteht durch Verknöcherungen im Bindegewebe des Integuments, es dient dem Schutz des Kopfes und trägt im Mundbreich die Zähne. Zusammen bilden die drei Skelettstrukturen die funktionelle Einheit Schädel (Cranium). Außer der (somatischen) Rumpfmuskulatur und dem Axialskelett liegen im Rumpf Kreislauf-, Atmungs-, Verdauungs-, Exkretions- und Fortpflanzungsorgane. Der Schwanz, der Abschnitt hinter der Afteröffnung, die das Ende der Leibeshöhle markiert, dient mit Muskeln und Schwanzflosse der Fortbewegung.

  7. Drugs of abuse specifically sensitize noradrenergic and serotonergic neurons via a non-dopaminergic mechanism.

    Science.gov (United States)

    Lanteri, Christophe; Salomon, Lucas; Torrens, Yvette; Glowinski, Jacques; Tassin, Jean-Pol

    2008-06-01

    A challenge in drug dependence is to delineate long-term neurochemical modifications induced by drugs of abuse. Repeated d-amphetamine was recently shown to disrupt a mutual regulatory link between noradrenergic and serotonergic neurons, thus inducing long-term increased responses to d-amphetamine and para-chloroamphetamine, respectively. We show here that such a sensitization of noradrenergic and serotonergic neurons also occurs following repeated treatment with cocaine, morphine, or alcohol, three compounds belonging to main groups of addictive substances. In all cases, this sensitization is prevented by alpha 1b-adrenergic and 5-HT2A receptors blockade, indicating the critical role of these receptors on long-term effects of drugs of abuse. However, repeated treatments with two non-addictive antidepressants, venlafaxine, and clorimipramine, which nevertheless inhibit noradrenergic and serotonergic reuptake, do not induce noradrenergic and serotonergic neurons sensitization. Similarly, this sensitization does not occur following repeated treatments with a specific inhibitor of dopamine (DA) reuptake, GBR12783. Moreover, we show that the effects of SCH23390, a D1 receptor antagonist known to inhibit development of d-amphetamine behavioral sensitization, are due to its 5-HT2C receptor agonist property. SCH23390 blocks amphetamine-induced release of norepinephrine and RS102221, a 5-HT2C antagonist, can reverse this inhibition as well as inhibition of noradrenergic sensitization and development of behavioral sensitization induced by repeated d-amphetamine. We propose that noradrenergic/serotonergic uncoupling is a common neurochemical consequence of repeated consumption of drugs of abuse, unrelated with DA release. Our data also suggest that compounds able to restore the link between noradrenergic and serotonergic modulatory systems could represent important therapeutic targets for investigation.

  8. Synthesis and structure of PbBipy2(1-B10H9S(CH3)2)2

    International Nuclear Information System (INIS)

    Orlova, A.M.; Sivaev, I.B.; Lagun, V.L.; Katser, S.B.; Solntsev, K.A.; Kuznetsov, N.T.

    1993-01-01

    Lead complex with B 10 H 9 S(CH 3 ) 2 - anion and 2,2'-bipyridine was synthesized and characterized. According to the data of X-ray diffraction analysis the crystals belong to monoclinic crystal system, sp. gr. P2 1 /a: a = 9.940(4), b 31.568(4), c = 13.458(2) A, β = 111.09(2) deg, V = 3940(2) A 3 , Z = 4. The structure consists of monomer units PbBipy 2 (1-B 10 H 9 S(CH 3 ) 2 ) 2 . The Pb-B distances are within 3.24-3.55 A. 15 refs., 1 fig., 2 tabs

  9. On the evidence for human use and control of fire at Schöningen.

    Science.gov (United States)

    Stahlschmidt, Mareike C; Miller, Christopher E; Ligouis, Bertrand; Hambach, Ulrich; Goldberg, Paul; Berna, Francesco; Richter, Daniel; Urban, Brigitte; Serangeli, Jordi; Conard, Nicholas J

    2015-12-01

    When and how humans began to control fire has been a central debate in Paleolithic archaeology for decades. Fire plays an important role in technology, social organization, subsistence, and manipulation of the environment and is widely seen as a necessary adaptation for the colonization of northern latitudes. Many researchers view purported hearths, burnt wooden implements, and heated flints from Schöningen as providing the best evidence for the control of fire in the Lower Paleolithic of Northern Europe. Here we present results of a multianalytical study of the purported hearths along with a critical examination of other possible evidence of human use or control of fire at Schöningen. We conclude that the analyzed features and artifacts present no convincing evidence for human use or control of fire. Our study also shows that a multianalytical, micro-contextual approach is the best methodology for evaluating claims of early evidence of human-controlled fire. We advise caution with macroscopic, qualitative identification of combustion features, burnt flint, and burnt wood without the application of such techniques as micromorphology, Fourier transform infrared (FTIR) spectroscopy, organic petrology, luminescence, and analysis of mineral magnetic parameters. The lack of evidence for the human control of fire at Schöningen raises the possibility that fire control was not a necessary adaptation for the human settlement of northern latitudes in the Lower Paleolithic. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Direct demonstration of D1 dopamine receptors in the bovine parathyroid gland using the D1 selective antagonist [125I]-SCH 23982

    International Nuclear Information System (INIS)

    Monsma, F.J. Jr.; Sibley, D.R.

    1989-01-01

    The presence of D1 dopamine receptors in the parathyroid gland has been proposed based on the demonstration of dopaminergic regulation of adenylate cyclase activity and parathyroid hormone release in dispersed bovine parathyroid cells. Using a radioiodinated D1 selective antagonist [125I]-SCH 23982, we have now directly labeled and characterized the D1 dopamine receptors in bovine parathyroid gland membranes. [125I]-SCH 23982 binds in a saturable manner with high affinity and low nonspecific binding to membranes prepared from bovine parathyroid glands. D1 dopamine receptors are present in this preparation at a concentration of approximately 130 fMoles/mg protein and [125I]-SCH 23982 binding increases with increasing protein concentration in a linear fashion. Determination of the Kd using the association (k1) and dissociation (k-1) rate constants revealed good agreement with the Kd determined by saturation analysis (390 pM vs. 682 pM, respectively). Inhibition of 0.3 nM [125I]-SCH 23982 binding by a series of dopaminergic antagonists verified the D1 nature of this binding site, exhibiting appropriate affinities and rank order of potency. The competition curves of all antagonists exhibited Hill coefficients that were not significantly different from 1. Inhibition of [125I]-SCH 23982 binding by dopamine and other dopaminergic agonists revealed the presence of high and low affinity agonist binding sites. Addition of 200 microM GppNHp effected a complete conversion of high affinity dopamine binding sites to a homogeneous population of low affinity dopamine sites. The D1 receptors identified in the parathyroid gland with [125I]-SCH 23982 appear to be pharmacologically identical with those previously characterized in the central nervous system

  11. "Wer wagt hier Theorie zu fordern": aspects théoriques du timbre chez Arnold Schönberg

    Directory of Open Access Journals (Sweden)

    Frédéric de Buzon

    2014-02-01

    Full Text Available Schönberg’s Harmonielehre finishes on the evocation of the melody of timbre (Klangfarbenmelodie. The aim of this article is to analyse the function of timbre in relation to musical theory by establishing a parallel between the positions expressed by Schönberg and preceding classical positions, namely Jean-Jaques Rousseau’s definition of timbre and Leibniz’s concept of “clear and confused” ideas. Operating in this context, what will be shown is that timbre, according to Leibniz’s description, is a distinguishing, yet undistinguished, quality and that, precisely for this reason, timbre has a limited function in composition.

  12. ANATOMY OF GYNURA AURANTIACA (BLUME) SCH.BIP. EX DC. (ASTERACEAE)

    OpenAIRE

    Rodica BERCU

    2014-01-01

    The paper presents a detailed histoanatomical description, of the vegetative organs (root, stem and leaf) and photographs as well of Gynura aurantiaca (Blume) Sch.Bip. ex DC. It was observed that the root have typical primary dictos structure. The stem has a differentiated in two regions cortex and the stele comprise one ring of open collateral vascular bundles with secondary xylem due to the cambium activity. The petiole anatomy is quite similar in its basic structure with the stem. The blad...

  13. D1- and D2-like dopamine receptors within the nucleus accumbens contribute to stress-induced analgesia in formalin-related pain behaviours in rats.

    Science.gov (United States)

    Faramarzi, G; Zendehdel, M; Haghparast, A

    2016-10-01

    Stressful experiences can produce analgesia, termed stress-induced analgesia (SIA). Meanwhile, it has been widely established that the mesolimbic dopamine pathway and nucleus accumbens (NAc) have a profound role in pain modulation. In this study, we examined the role of accumbal dopamine receptors in antinociception caused by forced swim stress (FSS) in order to understand more about the function of these receptors within the NAc in FSS-induced analgesia. Stereotaxic surgery was unilaterally performed on adult male Wistar rats weighing 230-250 g (some on the left and some on the right side of the midline). Two supergroups were microinjected into the NAc with a D1-like dopamine receptor antagonist, SCH-23390, at doses of 0.25, 1 and 4 μg/0.5 μl saline per rat or Sulpiride as a D2-like dopamine receptor antagonist at the same doses [0.25, 1 and 4 μg/0.5 μl dimethyl sulfoxide (DMSO) per rat]; while their controls just received intra-accumbal saline or DMSO at 0.5 μl, respectively. The formalin test was performed after rats were subjected to FSS (6 min, 25 ± 1 °C) to assess pain-related behaviours. The results demonstrated that intra-accumbal infusions of SCH-23390 and Sulpiride dose-dependently reduced FSS-induced antinociception in both phases of the formalin test. However, the percentage decrease in area under the curve (AUC) values calculated for treatment groups compared to formalin-control group was more significant in the late phase than the early phase. Our findings suggest that D1- and D2-like dopamine receptors in the NAc are involved in stress-induced antinociceptive behaviours in the formalin test as an animal model of persistent inflammatory pain. Forced swim stress (FSS) induces the antinociception in both phases of formalin test. Blockade of accumbal dopamine receptors attenuate the antinociception induced by FSS. Stress-induced analgesia is dose-dependently reduced by dopamine receptor antagonists in both phases, although it is more

  14. [Henoch-Schönlein Purpura Presenting as Intussusception].

    Science.gov (United States)

    Kim, Keun Young

    2017-06-25

    Henoch-Schönlein purpura (HSP) is systemic vasculitis disease with various clinical manifestations. Gastrointestinal symptoms in patients with HSP are usually common, with an incidence rate of 62-90%. Most of these gastrointestinal symptoms occur after typical skin purpura, which is a very important clinical evidence for making a diagnosis of HSP. It is difficult to diagnose HSP without skin rash. About 25% of patients may experience gastrointestinal symptoms as their first symptoms. Herein, we report a case of ileo-colic intussusception associated with HSP in a 5-years-old girl presented with diffuse abdominal distension. Our patient did present any symptoms of HSP, such as purpura, arthralgia or arthritis, before surgery.

  15. The Piagetian "Schème": A Framework to Study Professional Learning through Conceptualization

    Science.gov (United States)

    Tourmen, Claire; Holgado, Otilia; Métral, Jean-françois; Mayen, Patrick; Olry, Paul

    2017-01-01

    Different theories of learning have been used in vocational education studies and Piaget is a common source of reference. Our intent is to present a specific and original way in which the Piagetian theory of "schèmes" has been developed since the 1990s in studies called "vocational didactics." Developed in French-speaking…

  16. schématisation de la relativité générale , tenseurs et relativité restreinte

    OpenAIRE

    Chabbi , Noureddine

    2018-01-01

    Ce travail qui s'intitule ''schématisation de la relativité générale , tenseurs et relativité restreinte '' prolonge et continue un précédant : '' schématisation de la relativité générale , espace-temps et gravitation '' paru sur ce site sous la référence 01337506 en date du 27/06/2016.L'attention est portée cette fois ci sur 2 autres supports de la théorie de la relativité générale, à savoir '' les tenseurs '' et '' la relativité restreinte ''.L'espace-temps courbe a été expliqué par la géom...

  17. The European saber-toothed cat (Homotherium latidens) found in the "Spear Horizon" at Schöningen (Germany).

    Science.gov (United States)

    Serangeli, Jordi; Van Kolfschoten, Thijs; Starkovich, Britt M; Verheijen, Ivo

    2015-12-01

    The 300,000 year old Lower Paleolithic site Schöningen 13 II-4 became world famous with the discovery of the oldest well-preserved and complete wooden spears. Through ongoing excavations, new archaeological discoveries of scientific importance are still being made from the same archaeological layer where the spears were found. In this context, remains of a rare carnivore species, the European saber-toothed cat (Homotherium latidens), were recovered. Here we present five teeth and one humerus fragment that are unambiguously from two individual saber-toothed cats. The humerus is a unique specimen; it shows evidence of hominin impacts and use as a percussor. The Homotherium remains from Schöningen are the best documented finds of this species in an archaeological setting and they are amongst the youngest specimens of Homotherium in Europe. The presence of this species as a carnivore competitor would certainly have impacted the lives of late Middle Pleistocene hominins. The discovery illustrates the possible day-to-day challenges that the Schöningen hominins would have faced and suggests that the wooden spears were not necessarily only used for hunting, but possibly also as a weapon for self-defense. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Role of the Dopaminergic System in the Acquisition, Expression and Reinstatement of MDMA-Induced Conditioned Place Preference in Adolescent Mice

    Science.gov (United States)

    Vidal-Infer, Antonio; Roger-Sánchez, Concepción; Daza-Losada, Manuel; Aguilar, María A.; Miñarro, José; Rodríguez-Arias, Marta

    2012-01-01

    Background The rewarding effects of 3,4-methylenedioxy-metamphetamine (MDMA) have been demonstrated in conditioned place preference (CPP) procedures, but the involvement of the dopaminergic system in MDMA-induced CPP and reinstatement is poorly understood. Methodology/Principal Findings In this study, the effects of the DA D1 antagonist SCH 23390 (0.125 and 0.250 mg/kg), the DA D2 antagonist Haloperidol (0.1 and 0.2 mg/kg), the D2 antagonist Raclopride (0.3 and 0.6 mg/kg) and the dopamine release inhibitor CGS 10746B (3 and 10 mg/kg) on the acquisition, expression and reinstatement of a CPP induced by 10 mg/kg of MDMA were evaluated in adolescent mice. As expected, MDMA significantly increased the time spent in the drug-paired compartment during the post-conditioning (Post-C) test, and a priming dose of 5 mg/kg reinstated the extinguished preference. The higher doses of Haloperidol, Raclopride and CGS 10746B and both doses of SCH 23390 blocked acquisition of the MDMA-induced CPP. However, only Haloperidol blocked expression of the CPP. Reinstatement of the extinguished preference was not affected by any of the drugs studied. Analysis of brain monoamines revealed that the blockade of CPP acquisition was accompanied by an increase in DA concentration in the striatum, with a concomitant decrease in DOPAC and HVA levels. Administration of haloperidol during the Post-C test produced increases in striatal serotonin, DOPAC and HVA concentrations. In mice treated with the higher doses of haloperidol and CGS an increase in SERT concentration in the striatum was detected during acquisition of the CPP, but no changes in DAT were observed. Conclusions/Significance These results demonstrate that, in adolescent mice, the dopaminergic system is involved in the acquisition and expression of MDMA-induced CPP, but not in its reinstatement. PMID:22916213

  19. DA1 receptors modulation in rat isolated trachea.

    Science.gov (United States)

    Cabezas, Gloria A; Velasco, Manuel

    2010-01-01

    We have previously demonstrated that low dose of inhaled dopamine (0.5-2 microg kg(-1) min(-1)) induces broncodilatacion in patients with acute asthma attack, suggesting that this dopamine effect is mediated by dopaminergic rather than by adrenergic receptors. To understand better these dopamine effect, rat tracheal smooth muscle was used as a model to evaluate the responses of beta2-, alpha1-, alpha2-adrenergic and DA1 and DA2 dopaminergic antagonists. Tracheal rings from male Sprague-Dawley rats (n = 90) were excised and placed in an organ bath containing modified Krebs-Ringer bicarbonate buffer at 37 degrees C, and gassed with O2 (95%) and CO2 (5%). Contractile responses were recorded with an isometric transducer in a polygraph (Letica, Spain). Contraction was induced by accumulative doses of acetylcholine (0.1, 0.3, 1, 3, 10 mM) or by electric field stimulation (10 Hz at 2 milliseconds), and accumulative doses of dopamine were added to the bath. Low concentration (0.1-0.3 mM) elicited a small initial contraction, followed by a marked relaxation. Cholinergic contraction was completely reversed at 6 mM of dopamine. This biphasic dopaminergic response was not blocked by incubation with beta2-adrenergic antagonist propranolol (0.1 microM), alpha1-antagonist, terazosin (0.1 mM), alpha2-antagonist, yohimbine (0.1 mM), or by DA2 antagonist metoclopramide (1-8 mM); DA1 antagonist SCH23390 (0.1 microM) produced a sustained increase of basal tone but did not block initial dopaminergic contraction and partially inhibited bronchodilator effect of dopamine. Dopaminergic relaxation in rat trachea is mediated by DA1 rather than by DA2 receptors; and adrenergic receptors are not involved in such dopamine-induced response. Finally, DA1 antagonist SCH23390 exerts intrinsic contractile activity on airway smooth muscle that deserves further research.

  20. Activation of D1 dopamine receptors induces emergence from isoflurane general anesthesia

    Science.gov (United States)

    Taylor, Norman E.; Chemali, Jessica J.; Brown, Emery N.; Solt, Ken

    2012-01-01

    BACKGROUND A recent study showed that methylphenidate induces emergence from isoflurane anesthesia. Methylphenidate inhibits dopamine and norepinephrine reuptake transporters. The objective of this study was to test the hypothesis that selective dopamine receptor activation induces emergence from isoflurane anesthesia. METHODS In adult rats, we tested the effects of chloro-APB (D1 agonist) and quinpirole (D2 agonist) on time to emergence from isoflurane general anesthesia. We then performed a dose–response study to test for chloro-APB-induced restoration of righting during continuous isoflurane anesthesia. SCH-23390 (D1 antagonist) was used to confirm that the effects induced by chloro-APB are specifically mediated by D1 receptors. In a separate group of animals, spectral analysis was performed on surface electroencephalogram recordings to assess neurophysiological changes induced by chloro-APB and quinpirole during isoflurane general anesthesia. RESULTS Chloro-APB decreased median time to emergence from 330s to 50s. The median difference in time to emergence between the saline control group (n=6) and the chloro-APB group (n = 6) was 222s (95% CI: 77–534s, Mann-Whitney test). This difference was statistically significant (p = 0.0082). During continuous isoflurane anesthesia, chloro-APB dose-dependently restored righting (n = 6) and decreased electroencephalogram delta power (n = 4). These effects were inhibited by pretreatment with SCH-23390. Quinpirole did not restore righting (n = 6) and had no significant effect on the electroencephalogram (n = 4) during continuous isoflurane anesthesia. CONCLUSIONS Activation of D1 receptors by chloro-APB decreases time to emergence from isoflurane anesthesia, and produces behavioral and neurophysiological evidence of arousal during continuous isoflurane anesthesia. These findings suggest that selective activation of a D1 receptor-mediated arousal mechanism is sufficient to induce emergence from isoflurane general

  1. Systemic catechol-O-methyl transferase inhibition enables the D1 agonist radiotracer R-[11C]SKF 82957

    International Nuclear Information System (INIS)

    Palner, Mikael; McCormick, Patrick; Parkes, Jun; Knudsen, Gitte M.; Wilson, Alan A.

    2010-01-01

    Introduction: R-[ 11 C]-SKF 82957 is a high-affinity and potent dopamine D 1 receptor agonist radioligand, which gives rise to a brain-penetrant lipophilic metabolite. In this study, we demonstrate that systemic administration of catechol-O-methyl transferase (COMT) inhibitors blocks this metabolic pathway, facilitating the use of R-[ 11 C]-SKF 82957 to image the high-affinity state of the dopamine D 1 receptor with PET. Methods: R-[ 11 C]SKF 82957 was administered to untreated and COMT inhibitor-treated conscious rats, and the radioactive metabolites present in the brain and plasma were quantified by HPLC. Under optimal conditions, cerebral uptake and dopamine D 1 binding of R-[ 11 C]SKF 82957 were measured ex vivo. In addition, pharmacological challenges with the receptor antagonist SCH 23390, amphetamine, the dopamine reuptake inhibitor RTI-32 and the dopamine hydroxylase inhibitor α-methyl-p-tyrosine were performed to study the specificity and sensitivity of R-[ 11 C]-SKF 82957 dopamine D 1 binding in COMT-inhibited animals. Results: Treatment with the COMT inhibitor tolcapone was associated with a dose-dependent (EC 90 5.3±4.3 mg/kg) reduction in the lipophilic metabolite. Tolcapone treatment (20 mg/kg) also resulted in a significant increase in the striatum/cerebellum ratio of R-[ 11 C]SKF 82957, from 15 (controls) to 24. Treatment with the dopamine D 1 antagonist SCH 23390 reduced the striatal binding to the levels of the cerebellum, demonstrating a high specificity and selectivity of R-[ 11 C]SKF 82957 binding. Conclusions: Pre-treatment with the COMT inhibitor tolcapone inhibits formation of an interfering metabolite of R-[ 11 C]SKF 82957. Under such conditions, R-[ 11 C]SKF 82957 demonstrates high potential as the first agonist radiotracer for imaging the dopamine D 1 receptor by PET.

  2. Independent mediation of unconditioned motor behavior by striatal D1 and D2 receptors in rats depleted of dopamine as neonates.

    Science.gov (United States)

    Bruno, J P; Byrnes, E M; Johnson, B J

    1995-11-01

    The effects of systemic administration of DA receptor antagonists suggest that unconditioned motor behavior in rats depleted of DA as neonates continues to be dependent upon dopaminergic transmission, yet the specific contribution of D1 and D2 receptors to these behaviors has been altered. The purpose of the present study was to determine whether these depletion-induced receptor changes are occurring at the level of striatal DA terminals and their targets. The ability of bilateral intrastriatal injections (0.5 microliter) of DA receptor antagonists to induce motoric deficits was determined in adult rats treated with vehicle or 6-OHDA (100 micrograms, intraventricular) on postnatal day 3. Administration of the D1-like antagonist SCH 23390 (0.5-2.0 micrograms) or the D2-like antagonist clebopride (1.0-4.0 micrograms) induced dose-dependent akinesia, catalepsy, and somatosensory neglect in vehicle-treated controls. In contrast, neither antagonist produced deficits in rats depleted of forebrain DA as neonates. However, combined administration of SCH 23390 + clebopride induced similar akinesia, catalepsy, and somatosensory neglect in both controls and DA depleted animals. Animals depleted of DA were more sensitive than controls to the low doses of this combined D1 + D2 antagonism. These results demonstrate that activation of striatal DA receptors remains necessary for unconditioned motor behavior in rats depleted of DA as neonates. However, the specific contributions of D1- and D2-like receptors to these behaviors differ between intact animals and those depleted of DA as neonates. The ability of endogenous DA acting at either D1 or D2 receptors to support spontaneous motor behavior in rats depleted of DA as neonates may contribute to their relative sparing from parkinsonian deficits.

  3. Role of D1- and D2-like dopaminergic receptors in the nucleus accumbens in modulation of formalin-induced orofacial pain: Involvement of lateral hypothalamus.

    Science.gov (United States)

    Shafiei, Iman; Vatankhah, Mahsaneh; Zarepour, Leila; Ezzatpanah, Somayeh; Haghparast, Abbas

    2018-05-01

    The role of dopaminergic system in modulation of formalin-induced orofacial nociception has been established. The present study aims to investigate the role of dopaminergic receptors in the nucleus accumbens (NAc) in modulation of nociceptive responses induced by formalin injection in the orofacial region. One hundred and six male Wistar rats were unilaterally implanted with two cannulae into the lateral hypothalamus (LH) and NAc. Intra-LH microinjection of carbachol, a cholinergic receptor agonist, was done 5min after intra-accumbal administration of different doses of SCH23390 (D1-like receptor antagonist) or sulpiride (D2-like receptor antagonist). After 5min, 50μl of 1% formalin was subcutaneously injected into the upper lip for inducing the orofacial pain. Carbachol alone dose-dependently reduced both phases of the formalin-induced orofacial pain. Intra-accumbal administration of SCH23390 (0.25, 1 and 4μg/0.5μl saline) or sulpiride (0.25, 1 and 4μg/0.5μl DMSO) before LH stimulation by carbachol (250nM/0.5μl saline) antagonized the antinociceptive responses during both phases of orofacial formalin test. The effects of D1- and D2-like receptor antagonism on the LH stimulation-induced antinociception were almost similar during the early phase. However, compared to D1-like receptor antagonism, D2-like receptor antagonism was a little more effective but not significant, at blocking the LH stimulation-induced antinociception during the late phase of formalin test. The findings revealed that there is a direct or indirect neural pathway from the LH to the NAc which is at least partially contributed to the modulation of formalin-induced orofacial nociception through recruitment of both dopaminergic receptors in this region. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Histamine H3 receptor activation selectively inhibits dopamine D1 receptor-dependent [3H]GABA release from depolarization-stimulated slices of rat substantia nigra pars reticulata

    International Nuclear Information System (INIS)

    Aceves, J.; Young, J.M.; Arias-Montano, J.A.; Floran, B.; Garcia, M.

    1997-01-01

    The release of [ 3 H]GABA from slices of rat substantia nigra pars reticulata induced by increasing extracellular K + from 6 to 15 mM in the presence of 10 μM sulpiride was inhibited by 73±3% by 1 μM SCH 23390, consistent with a large component of release dependent upon D 1 receptor activation. The histamine H 3 receptor-selective agonist immepip (1 μM) and the non-selective agonist histamine (100 μM) inhibited [ 3 H]GABA release by 78±2 and 80±2%, respectively. The inhibition by both agonists was reversed by the H 3 receptor antagonist thioperamide (1 μM). However, in the presence of 1 μM SCH 23390 depolarization-induced release of [ 3 H]GABA was not significantly decreased by 1 μM immepip. In rats depleted of dopamine by pretreatment with reserpine, immepip no longer inhibited control release of [ 3 H]GABA, but in the presence of 1 μM SKF 38393, which produced a 7±1-fold stimulation of release, immepip reduced the release to a level not statistically different from that in the presence of immepip alone. Immepip (1 μM) also inhibited the depolarization-induced release of [ 3 H]dopamine from substantia nigra pars reticulata slices, by 38±3%.The evidence is consistent with the proposition that activation of histamine H 3 receptors leads to the selective inhibition of the component of depolarization-induced [ 3 H]GABA release in substantia nigra pars reticulata slices which is dependent upon D 1 receptor activation. This appears to be largely an action at the terminals of the striatonigral GABA projection neurons, which may be enhanced by a partial inhibition of dendritic [ 3 H]dopamine release. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  5. D1-like dopamine receptors downregulate Na+-K+-ATPase activity and increase cAMP production in the posterior gills of the blue crab Callinectes sapidus.

    Science.gov (United States)

    Arnaldo, Francis B; Villar, Van Anthony M; Konkalmatt, Prasad R; Owens, Shaun A; Asico, Laureano D; Jones, John E; Yang, Jian; Lovett, Donald L; Armando, Ines; Jose, Pedro A; Concepcion, Gisela P

    2014-09-15

    Dopamine-mediated regulation of Na(+)-K(+)-ATPase activity in the posterior gills of some crustaceans has been reported to be involved in osmoregulation. The dopamine receptors of invertebrates are classified into three groups based on their structure and pharmacology: D1- and D2-like receptors and a distinct invertebrate receptor subtype (INDR). We tested the hypothesis that a D1-like receptor is expressed in the blue crab Callinectes sapidus and regulates Na(+)-K(+)-ATPase activity. RT-PCR, using degenerate primers, showed the presence of D1βR mRNA in the posterior gill. The blue crab posterior gills showed positive immunostaining for a dopamine D5 receptor (D5R or D1βR) antibody in the basolateral membrane and cytoplasm. Confocal microscopy showed colocalization of Na(+)-K(+)-ATPase and D1βR in the basolateral membrane. To determine the effect of D1-like receptor stimulation on Na(+)-K(+)-ATPase activity, intact crabs acclimated to low salinity for 6 days were given an intracardiac infusion of the D1-like receptor agonist fenoldopam, with or without the D1-like receptor antagonist SCH23390. Fenoldopam increased cAMP production twofold and decreased Na(+)-K(+)-ATPase activity by 50% in the posterior gills. This effect was blocked by coinfusion with SCH23390, which had no effect on Na(+)-K(+)-ATPase activity by itself. Fenoldopam minimally decreased D1βR protein expression (10%) but did not affect Na(+)-K(+)-ATPase α-subunit protein expression. This study shows the presence of functional D1βR in the posterior gills of euryhaline crabs chronically exposed to low salinity and highlights the evolutionarily conserved function of the dopamine receptors on sodium homeostasis. Copyright © 2014 the American Physiological Society.

  6. Dopamine enhances duodenal epithelial permeability via the dopamine D5 receptor in rodent.

    Science.gov (United States)

    Feng, X-Y; Zhang, D-N; Wang, Y-A; Fan, R-F; Hong, F; Zhang, Y; Li, Y; Zhu, J-X

    2017-05-01

    The intestinal barrier is made up of epithelial cells and intercellular junctional complexes to regulate epithelial ion transport and permeability. Dopamine (DA) is able to promote duodenal epithelial ion transport through D1-like receptors, which includes subtypes of D 1 (D 1 R) and D 5 (D 5 R), but whether D1-like receptors influence the duodenal permeability is unclear. FITC-dextran permeability, short-circuit current (I SC ), Western blot, immunohistochemistry and ELISA were used in human D 5 R transgenic mice and hyperendogenous enteric DA (HEnD) rats in this study. Dopamine induced a downward deflection in I SC and an increase in FITC-dextran permeability of control rat duodenum, which were inhibited by the D1-like receptor antagonist, SCH-23390. However, DA decreased duodenal transepithelial resistance (TER), an effect also reversed by SCH-23390. A strong immunofluorescence signal for D 5 R, but not D 1 R, was observed in the duodenum of control rat. In human D 5 R knock-in transgenic mice, duodenal mucosa displayed an increased basal I SC with high FITC-dextran permeability and decreased TER with a lowered expression of tight junction proteins, suggesting attenuated duodenal barrier function in these transgenic mice. D 5 R knock-down transgenic mice manifested a decreased basal I SC with lowered FITC-dextran permeability. Moreover, an increased FITC-dextran permeability combined with decreased TER and tight junction protein expression in duodenal mucosa were also observed in HEnD rats. This study demonstrates, for the first time, that DA enhances duodenal permeability of control rat via D 5 R, which provides new experimental and theoretical evidence for the influence of DA on duodenal epithelial barrier function. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  7. Control of the subthalamic innervation of substantia nigra pars reticulata by D1 and D2 dopamine receptors.

    Science.gov (United States)

    Ibañez-Sandoval, Osvaldo; Hernández, Adán; Florán, Benjamin; Galarraga, Elvira; Tapia, Dagoberto; Valdiosera, Rene; Erlij, David; Aceves, Jorge; Bargas, José

    2006-03-01

    The effects of activating dopaminergic D1 and D2 class receptors of the subthalamic projections that innervate the pars reticulata of the subtantia nigra (SNr) were explored in slices of the rat brain using the whole cell patch-clamp technique. Excitatory postsynaptic currents (EPSCs) that could be blocked by 6-cyano-7-nitroquinoxalene-2,3-dione and D-(-)-2-amino-5-phosphonopentanoic acid were evoked onto reticulata GABAergic projection neurons by local field stimulation inside the subthalamic nucleus in the presence of bicuculline. Bath application of (RS)-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrochloride (SKF-38393), a dopaminergic D1-class receptor agonist, increased evoked EPSCs by approximately 30% whereas the D2-class receptor agonist, trans-(-)-4aR-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo(3,4-g)quinoline (quinpirole), reduced EPSCs by approximately 25%. These apparently opposing actions were blocked by the specific D1- and D2-class receptor antagonists: R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetra-hydro-1H-3-benzazepinehydrochloride (SCH 23390) and S-(-)-5-amino-sulfonyl-N-[(1-ethyl-2-pyrrolidinyl)-methyl]-2-methoxybenzamide (sulpiride), respectively. Both effects were accompanied by changes in the paired-pulse ratio, indicative of a presynaptic site of action. The presynaptic location of dopamine receptors at the subthalamonigral projections was confirmed by mean-variance analysis. The effects of both SKF-38393 and quinpirole could be observed on terminals contacting the same postsynaptic neuron. Sulpiride and SCH 23390 enhanced and reduced the evoked EPSC, respectively, suggesting a constitutive receptor activation probably arising from endogenous dopamine. These data suggest that dopamine presynaptically modulates the subthalamic projection that targets GABAergic neurons of the SNr. Implications of this modulation for basal ganglia function are discussed.

  8. Chronic restraint stress during withdrawal increases vulnerability to drug priming-induced cocaine seeking via a dopamine D1-like receptor-mediated mechanism.

    Science.gov (United States)

    Ball, Kevin T; Stone, Eric; Best, Olivia; Collins, Tyler; Edson, Hunter; Hagan, Erin; Nardini, Salvatore; Neuciler, Phelan; Smolinsky, Michael; Tosh, Lindsay; Woodlen, Kristin

    2018-06-01

    A major obstacle in the treatment of individuals with cocaine addiction is their high propensity for relapse. Although the clinical scenario of acute stress-induced relapse has been well studied in animal models, few pre-clinical studies have investigated the role of chronic stress in relapse or the interaction between chronic stress and other relapse triggers. We tested the effect of chronic restraint stress on cocaine seeking in rats using both extinction- and abstinence-based animal relapse models. Rats were trained to press a lever for I.V. cocaine infusions (0.50 mg/kg/infusion) paired with a discrete tone + light cue in daily 3-h sessions. Following self-administration, rats were exposed to a chronic restraint stress procedure (3 h/day) or control procedure (unstressed) during the first seven days of a 13-day extinction period during which lever presses had no programmed consequences. This was followed by cue- and cocaine priming-induced drug seeking tests. In a separate group of rats, cocaine seeking was assessed during forced abstinence both before and after the same chronic stress procedure. A history of chronic restraint stress was associated with increased cocaine priming-induced drug seeking, an effect attenuated by co-administration of SCH-23390 (10.0 μg/kg; i.p.), a dopamine D 1 -like receptor antagonist, with daily restraint. Repeated SCH-23390 administration but not stress during extinction increased cue-induced reinstatement. Exposure to chronic stress during early withdrawal may confer lasting vulnerability to some types of relapse, and dopamine D 1 -like receptors appear to mediate both chronic stress effects on cocaine seeking and extinction of cocaine seeking. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Henoch-schönlein purpura (HSP) in an adult

    Science.gov (United States)

    Negara, C. A.; Zubir, Z.

    2018-03-01

    Henoch-schönlein purpura (HSP) is vasculitis of the small vessels, the most common vasculitis of the childhood and is uncommon in adults. A case of HSP is reported in a 36-year-old female with ten days history of multiple palpable purpura on region antebrachii, region femoralis and cruris dextra et sinistra. Burn sensation in both legs, pain sensation on knees joint and ankles joint and bloody stools were found. History of a cough and sore throat are often to be a presentation. Laboratory examination was mild anemia, mild leukocytes, ASTO (antistreptolysin titer O): children due to an increased risk of disorders of the renal.

  10. Warfarin-induced toxic epidermal necrolysis in combination therapy of Henoch-Schönlein purpura nephritis: a case report.

    Science.gov (United States)

    Kasahara, Katsuaki; Gotoh, Yoshimitsu; Kuroyanagi, Yoshiyuki; Nagano, China

    2017-07-14

    Toxic epidermal necrolysis (TEN) is a rare life-threatening condition almost exclusively attributed to drugs. The main etiologic factors for TEN are sulphonamides, anticonvulsants, and antibiotics; however, there are no published reports of warfarin causing TEN. We present the case of a 3-year-old patient who developed TEN while receiving treatment for Henoch-Schönlein purpura nephritis (HSPN). With multiple-drug therapy comprising prednisolone, mizoribine, dipyridamole, and warfarin, it is difficult to detect which drug is the causative agent. While in most cases, diagnosis of the causative drug is based on clinical history without a lymphocyte transformation test (LTT), we performed the test three times and identified the causative drug as warfarin at the late phase. We continued HSPN treatment without warfarin, and results showed good renal function without life-threatening complications. To our knowledge, this is the first report about TEN caused by warfarin. Repeated LTTs could be useful for identifying TEN-causative drugs even in the late phase.

  11. EPICOG-SCH: A brief battery to screen cognitive impact of schizophrenia in stable outpatients

    Directory of Open Access Journals (Sweden)

    Silvia Zaragoza Domingo

    2017-06-01

    The EPICOG-SCH proved to be a useful brief tool to screen for the cognitive impact of schizophrenia, and its regression-weighted Composite Score was an efficient complement to clinical interviews for confirming patients' potential functional outcomes and can be useful for monitoring cognition during routine outpatient follow-up visits.

  12. Von der Geschäftsidee zum Businessplan Businessplan für Schülerunternehmen

    NARCIS (Netherlands)

    Prof. Dr. Ingo Bieberstein; Dr. Ulrich Scholz

    2011-01-01

    Das Buch gibt einen Einblick in die Grundlagen der Betriebswirtschaftslehre und will das Verständnis für ökonomische Zusammenhänge fördern. Das Buch gibt eine Anleitung zur Erstellung eines Businessplans mit vielen praktischen Beispielen. Die Zielgruppe dieses Buches sind Schüler, aber auch

  13. Repeated stressful experiences differently affect brain dopamine receptor subtypes

    International Nuclear Information System (INIS)

    Puglisi-Allegra, S.; Cabib, S.; Kempf, E.; Schleef, C.

    1991-01-01

    The binding of tritiated spiperone (D2 antagonist) and tritiated SCH 23390 (D1 antagonist), in vivo, was investigated in the caudatus putamen (CP) and nucleus accumbens septi (NAS) of mice submitted to ten daily restraint stress sessions. Mice sacrificed 24 hr after the last stressful experience presented a 64% decrease of D2 receptor density (Bmax) but no changes in D1 receptor density in the NAS. In the CP a much smaller (11%) reduction of D2 receptor density was accompanied by a 10% increase of D1 receptors. These results show that the two types of dopamine (DA) receptors adapt in different or even opposite ways to environmental pressure, leading to imbalance between them

  14. Alfred Schütz’s writings from the perspective of a theory of action’s creativity

    Directory of Open Access Journals (Sweden)

    Javier L. Cristiano

    2013-06-01

    Full Text Available The article proposes a review of the work of Schütz from the question about “creativity” of social action, which was not made expressly by the author but it is in his writings an important principle of response. After positioning the subject in some coordinates of the current sociological discussion, we present four specific fields from schütz’ contributions: the ability to expand and make a creative use of “the social heritage of knowledge”, the individual and collective capacity to imagine action projects, the ability to create and use symbols, and producing with them exclusive worlds of imaginary existence, as well as the ability to give birth to new experiences. It is stated that these four fields outline the contours of a phenomenology of creativity of action, which sets out some open fields for further research.

  15. Inhibition of the mesoamygdala dopaminergic pathway impairs the retrieval of conditioned fear associations.

    Science.gov (United States)

    Nader, K; LeDoux, J E

    1999-10-01

    Previous findings have demonstrated that systemic dopaminergic manipulations impair the retrieval of Pavlovian conditioned fear. A second-order fear-conditioning paradigm was used to test whether the dopaminergic projection from the ventral tegmental area (VTA) to the lateral and basal amygdala (LBA) can affect conditioned fear. Phase 1 entailed conditioned stimulus-unconditioned stimulus (CS1-US) pairings. In Phase 2, drugs were infused in either the LBA or VTA prior to pairings of CS2 (a second cue) with CS1. In Phase 3, freezing behavior elicited by CS2 was tested without drugs. Infusions of the D2 agonist quinpirole into the VTA or of the D1 antagonist SCH 23390 into the LBA caused a decrease in freezing to CS2. Both manipulations decrease D1 receptor activation in the LBA. Infusions of the D1 agonist SKF 38393 into the LBA had no effect. This pattern of results is consistent with the hypothesis that the VTA-LBA dopaminergic projection modulates the retrieval of an association between a CS and footshock US.

  16. On 18 December 2004, the President of the Swiss Electro-technical Committee, Martin Reichle (left), presented the award to Helmut Schönbacher.

    CERN Multimedia

    2005-01-01

    Helmut Schönbacher, previously of CERN's Safety Commission, has received the 1906 Award of the International Electrotechnical Commission (IEC) for his standardization work on the influence of ionizing radiation on insulating materials. From 1986 until 2004, Schönbacher led a working group on radiation composed of internationally recognized experts, which edited standards in the IEC 60544 series on the determination of the effects of ionizing radiation on electrically insulating materials.

  17. Dopamine modulates memory consolidation of discrimination learning in the auditory cortex.

    Science.gov (United States)

    Schicknick, Horst; Reichenbach, Nicole; Smalla, Karl-Heinz; Scheich, Henning; Gundelfinger, Eckart D; Tischmeyer, Wolfgang

    2012-03-01

    In Mongolian gerbils, the auditory cortex is critical for discriminating rising vs. falling frequency-modulated tones. Based on our previous studies, we hypothesized that dopaminergic inputs to the auditory cortex during and shortly after acquisition of the discrimination strategy control long-term memory formation. To test this hypothesis, we studied frequency-modulated tone discrimination learning of gerbils in a shuttle box GO/NO-GO procedure following differential treatments. (i) Pre-exposure of gerbils to the frequency-modulated tones at 1 day before the first discrimination training session severely impaired the accuracy of the discrimination acquired in that session during the initial trials of a second training session, performed 1 day later. (ii) Local injection of the D1/D5 dopamine receptor antagonist SCH-23390 into the auditory cortex after task acquisition caused a discrimination deficit of similar extent and time course as with pre-exposure. This effect was dependent on the dose and time point of injection. (iii) Injection of the D1/D5 dopamine receptor agonist SKF-38393 into the auditory cortex after retraining caused a further discrimination improvement at the beginning of subsequent sessions. All three treatments, which supposedly interfered with dopamine signalling during conditioning and/or retraining, had a substantial impact on the dynamics of the discrimination performance particularly at the beginning of subsequent training sessions. These findings suggest that auditory-cortical dopamine activity after acquisition of a discrimination of complex sounds and after retrieval of weak frequency-modulated tone discrimination memory further improves memory consolidation, i.e. the correct association of two sounds with their respective GO/NO-GO meaning, in support of future memory recall. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  18. Katrin Schütz: Geschlechterentwürfe im literarischen Werk von Lou Andreas-Salomé unter Berücksichtigung ihrer Geschlechtertheorie. Würzburg: Verlag Königshausen & Neumann 2008

    Directory of Open Access Journals (Sweden)

    Romana Weiershausen

    2009-03-01

    Full Text Available Katrin Schütz hat eine Studie zu Geschlechterkonzeptionen in Lou Andreas-Salomés Frühwerk vorgelegt, in der auch die bislang wenig berücksichtigten literarischen Texte der Autorin ausgewertet werden. Die Anlage zielt auf eine Überblicksdarstellung, hinter der die differenzierende Reflexion der einzelnen Thesen zurück steht: Schütz geht es um die Konturierung einer Typologie. Durch die erweiterte Textgrundlage wird dabei Neues erschlossen, woraus sich anregende Impulse für die Jahrhundertwende-Forschung ergeben.Katrin Schütz’s study of gender conceptions in Lou Andreas-Salomé’s early work considers those literary texts often ignored by scholarship. The study is constructed as an overview, in light of which a differentiated reflection on the individual theses falls short: Schütz intends to formulate a typology. The expanded textual basis allows for the creation of something new, which will in turn provide inspirational impulses for turn-of-the-century research.

  19. Des schémas équivalents pour les circuits couplés multi-enroulements

    Science.gov (United States)

    Keradec, J. P.; Cogitore, B.; Laveuve, E.; Bensoam, M.

    1994-04-01

    The aim of this paper is to represent the electrical behaviour of any number of magnetically coupled windings with couplers and inductors. Two methods, mathematicaly justified, are proposed. The second one introduces only positive inductances. As an exemple, it is applied to the representation of a three column three phase transformer. The obtained circuits supply the requisite guide to design more complete circuits which allow the high frequency behaviour of wound components to be taken into account, especialy in electronics simulation softwares. Le but de cet article est de traduire le comportement électrique d'un nombre quelconque d'enroulements magnétiquement couplés, par des coupleurs et des inductances. Deux méthodes, établies mathématiquement, sont proposées. La seconde n'introduit que des inductances positives. A titre d'exemple, elle est appliquée à la représentation d'un transformateur triphasé à trois colonnes. Les schémas obtenus fournissent l'indispensable ossature de schémas plus complets, aptes à représenter le comportement haute fréquence des composants bobinés, notamment dans un logiciel de simulation électronique.

  20. Entfremdung als Strukturmoment von Unterricht? Eine Fallstudie zur Arbeit eines Schülers an der Tafel aus der Sicht der pädagogischen Unterrichtsforschung

    OpenAIRE

    Twardella, Johannes

    2010-01-01

    "In den 70er Jahren des 20. Jahrhunderts beobachtete Jules Henry im Rahmen seiner ethnographischen Schulforschungen die Arbeit eines Schülers an der Tafel und interpretierte sie aus einer sozialpsychologischen Perspektive heraus als einen Prozess, in dem ein Schüler lernt, was "Entfremdung" ist. Ausgehend von dieser Deutung wird in dem vorliegenden Aufsatz der Frage nachgegangen, ob der Begriff der Entfremdung auch heute noch für die Erforschung von Unterricht fruchtbar gemacht werden kann. D...

  1. Untersuchungen zum Einfluss der Betriebsbedingungen auf die Schädigung und Instandhaltung von Turboluftstrahltriebwerken

    OpenAIRE

    Müller, Matthias H.

    2013-01-01

    Langfristige Instandhaltungsverträge und der anhaltende Kostendruck haben die Notwendigkeit einer zuverlässigen Vorhersage und einer Reduzierung der Kosten für die Instandhaltung von Turboluftstrahltriebwerken zur Folge. Die Instandhaltungsbedürftigkeit und Zuverlässigkeit von Turboluftstrahltriebwerken wird wesentlich durch die betreibertypischen Betriebsbedingungen und die auftretenden Schädigungsmechanismen beeinflusst. Der Verlauf der Bauteilschädigung wird neben den Betriebsbedingungen d...

  2. Oral tremor induced by the muscarinic agonist pilocarpine is suppressed by the adenosine A2A antagonists MSX-3 and SCH58261, but not the adenosine A1 antagonist DPCPX.

    Science.gov (United States)

    Collins, Lyndsey E; Galtieri, Daniel J; Brennum, Lise T; Sager, Thomas N; Hockemeyer, Jörg; Müller, Christa E; Hinman, James R; Chrobak, James J; Salamone, John D

    2010-02-01

    Tremulous jaw movements in rats, which can be induced by dopamine (DA) antagonists, DA depletion, and cholinomimetics, have served as a useful model for studies of tremor. Although adenosine A(2A) antagonists can reduce the tremulous jaw movements induced by DA antagonists and DA depletion, there are conflicting reports about the interaction between adenosine antagonists and cholinomimetic drugs. The present studies investigated the ability of adenosine antagonists to reverse the tremorogenic effect of the muscarinic agonist pilocarpine. While the adenosine A(2A) antagonist MSX-3 was incapable of reversing the tremulous jaw movements induced by the 4.0mg/kg dose of pilocarpine, both MSX-3 and the adenosine A(2A) antagonist SCH58261 reversed the tremulous jaw movements elicited by 0.5mg/kg pilocarpine. Systemic administration of the adenosine A(1) antagonist DPCPX failed to reverse the tremulous jaw movements induced by either an acute 0.5mg/kg dose of the cholinomimetic pilocarpine or the DA D2 antagonist pimozide, indicating that the tremorolytic effects of adenosine antagonists may be receptor subtype specific. Behaviorally active doses of MSX-3 and SCH 58261 showed substantial in vivo occupancy of A(2A) receptors, but DPCPX did not. The results of these studies support the use of adenosine A(2A) antagonists for the treatment of tremor. Copyright 2009 Elsevier Inc. All rights reserved.

  3. Saussurea tridactyla Sch. Bip.-derived polysaccharides and flavones reduce oxidative damage in ultraviolet B-irradiated HaCaT cells via a p38MAPK-independent mechanism

    Directory of Open Access Journals (Sweden)

    Guo Y

    2016-01-01

    Full Text Available Yan Guo,1 Juan Sun,2 Juan Ye,1 Wenyu Ma,1 Hualing Yan,1 Gang Wang1 1Department of Dermatology and Venereology, Affiliated Hospital of Qinghai University, 2Department of Anatomy, Qinghai University Medical College, Xining, People’s Republic of China Objective: To investigate whether Saussurea tridactyla Sch. Bip.-derived polysaccharides and flavones exert apoptosis-inhibiting effects in ultraviolet B (UVB-irradiated HaCaT cells.Methods: We divided HaCaT cells into low radiation UVB and high radiation UVB groups. Low radiation UVB and high radiation UVB groups were further divided into a control group, UVB radiation group (UVB group, S. tridactyla Sch. Bip.-derived polysaccharides and flavones low-dose group, and S. tridactyla Sch. Bip.-derived polysaccharides and flavones high-dose group. Cell viability and morphology were assayed by MTT and trypan blue staining. Superoxide dismutase activity, glutathione content, malondialdehyde content, and catalase activity test kits were used to detect superoxide dismutase activity, glutathione content, malondialdehyde content, and catalase activity, respectively. Cell apoptosis, intracellular Ca2+ levels, and mitochondrial membrane potential (ΔΨ were detected by flow cytometry. Protein levels were analyzed by Western blotting and immunofluorescence.Results: S. tridactyla Sch. Bip.-derived polysaccharides and flavones were found to increase the absorbance of MTT, decrease cell death, alleviate the degree of cell edema, restore the cell morphology, reduce cell death fragments and chip phenomenon, increase superoxide dismutase activity, glutathione content, and catalase activity while decreasing the content of malondialdehyde, lowering the population of apoptotic cells, reducing the intracellular Ca2+ fluorescence, increasing the mitochondrial membrane potential (ΔΨ, increasing the expressions of p-38, p-53, Bcl-2, and decreasing the expressions of Bax and active-caspase-3.Conclusion: S. tridactyla Sch

  4. Systemic catechol-O-methyl transferase inhibition enables the D{sub 1} agonist radiotracer R-[{sup 11}C]SKF 82957

    Energy Technology Data Exchange (ETDEWEB)

    Palner, Mikael, E-mail: mikael.palner@nru.d [Neurobiology Research Unit, Rigshospitalet and University of Copenhagen, Copenhagen (Denmark); Center for Integrated Molecular Brain Imaging, Rigshospitalet (Denmark); McCormick, Patrick; Parkes, Jun [PET Center, Center for Addiction and Mental Health, Toronto, Ontario (Canada); Knudsen, Gitte M. [Neurobiology Research Unit, Rigshospitalet and University of Copenhagen, Copenhagen (Denmark); Center for Integrated Molecular Brain Imaging, Rigshospitalet (Denmark); Wilson, Alan A. [PET Center, Center for Addiction and Mental Health, Toronto, Ontario (Canada); Department of Psychiatry, University of Toronto, Toronto, Ontario (Canada)

    2010-10-15

    Introduction: R-[{sup 11}C]-SKF 82957 is a high-affinity and potent dopamine D{sub 1} receptor agonist radioligand, which gives rise to a brain-penetrant lipophilic metabolite. In this study, we demonstrate that systemic administration of catechol-O-methyl transferase (COMT) inhibitors blocks this metabolic pathway, facilitating the use of R-[{sup 11}C]-SKF 82957 to image the high-affinity state of the dopamine D{sub 1} receptor with PET. Methods: R-[{sup 11}C]SKF 82957 was administered to untreated and COMT inhibitor-treated conscious rats, and the radioactive metabolites present in the brain and plasma were quantified by HPLC. Under optimal conditions, cerebral uptake and dopamine D{sub 1} binding of R-[{sup 11}C]SKF 82957 were measured ex vivo. In addition, pharmacological challenges with the receptor antagonist SCH 23390, amphetamine, the dopamine reuptake inhibitor RTI-32 and the dopamine hydroxylase inhibitor {alpha}-methyl-p-tyrosine were performed to study the specificity and sensitivity of R-[{sup 11}C]-SKF 82957 dopamine D{sub 1} binding in COMT-inhibited animals. Results: Treatment with the COMT inhibitor tolcapone was associated with a dose-dependent (EC{sub 90} 5.3{+-}4.3 mg/kg) reduction in the lipophilic metabolite. Tolcapone treatment (20 mg/kg) also resulted in a significant increase in the striatum/cerebellum ratio of R-[{sup 11}C]SKF 82957, from 15 (controls) to 24. Treatment with the dopamine D{sub 1} antagonist SCH 23390 reduced the striatal binding to the levels of the cerebellum, demonstrating a high specificity and selectivity of R-[{sup 11}C]SKF 82957 binding. Conclusions: Pre-treatment with the COMT inhibitor tolcapone inhibits formation of an interfering metabolite of R-[{sup 11}C]SKF 82957. Under such conditions, R-[{sup 11}C]SKF 82957 demonstrates high potential as the first agonist radiotracer for imaging the dopamine D{sub 1} receptor by PET.

  5. Interaction between the dopaminergic and opioidergic systems in dorsal hippocampus in modulation of formalin-induced orofacial pain in rats.

    Science.gov (United States)

    Reisi, Zahra; Haghparast, Amir; Pahlevani, Pouyan; Shamsizadeh, Ali; Haghparast, Abbas

    2014-09-01

    The hippocampus is a region of the brain that serves several functions. The dopaminergic system acts through D1- and D2-like receptors to interfere in pain modulation and the opioid receptors play major roles in analgesic processes and there are obvious overlaps between these two systems. The present study investigated the interaction between the opioidergic and dopaminergic systems in the dorsal hippocampus (CA1) region for formalin-induced orofacial pain. Two guide cannulae were stereotaxically implanted in the CA1 region and morphine (0.5, 1, 2 and 4 μg/0.5 μl saline) and naloxone (0.3, 1 and 3 μg/0.5 μl saline) were used as the opioid receptor agonist and antagonist, respectively. SKF-38393 (1 μg/0.5 μl saline) was used as a D1-like receptor agonist, quinpirole (2 μg/0.5 μl saline) as a D2-like receptor agonist, SCH-23390 (0.5 μg/0.5 μl saline) as a D1-like receptor antagonist and sulpiride (3 μg/0.5 μl DMSO) as a D2-like receptor antagonist. To induce orofacial pain, 50 μl of 1% formalin was subcutaneously injected into the left side of the upper lip. Our results showed that different doses of morphine significantly reduced orofacial pain in both phases induced by formalin. Naloxone (1 and 3 μg) reversed morphine induced analgesia in CA1. SKF-38393 and quinpirole with naloxone (1 μg) significantly decreased formalin-induced orofacial pain in both phases. SCH-23390 had no effect on the antinociceptive response of morphine in both phases of orofacial pain. Sulpiride reversed the antinociceptive effects of morphine only in the first phase, but this result was not significant. Our findings suggest that there is cross-talk between the opioidergic and dopaminergic systems. Opioidergic neurons also exerted antinociceptive effects by modulation of the dopaminergic system in the CA1 region of the brain. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Mechanism of synergistic action following co-treatment with pramipexole and fluoxetine or sertraline in the forced swimming test in rats.

    Science.gov (United States)

    Rogóz, Zofia; Skuza, Grazyna

    2006-01-01

    The aim of the present study was to examine the effect of combined treatment of male Wistar rats with pramipexole and fluoxetine or sertraline in the forced swimming test. The obtained results showed that co-treatment with pramipexole (0.1 mg/kg) and fluoxetine (10 mg/kg) or sertraline (5 mg/kg) (in doses inactive per se) exhibited antidepressant-like activity in the forced swimming test. Sulpiride (a dopamine D(2/3) receptor antagonist) and WAY 100635 (a 5-HT(1A) receptor antagonist), either being ineffective in the forced swimming test, inhibited the antidepressant-like effect induced by co-administration of pramipexole and fluoxetine or sertraline. However, SCH 23390 (a dopamine D(1) receptor antagonist) only partly did not alter the effect of pramipexole given jointly with antidepressant drugs; on the other hand, S 33084 (a dopamine D(3) receptor antagonist) only partly decreased (in a statistically insignificant manner) that effect. Moreover, progesterone and BD 1047 (a sigma(1) receptor antagonist) counteracted the antidepressant-like effect induced by co-administration of pramipexole and sertraline (but not pramipexole and fluoxetine). In that test, active behavior did not reflect the increases in general activity, since combined administration of pramipexole and fluoxetine or sertraline failed to enhance the locomotor activity of rats. None of the tested drugs (SCH 23390, sulpiride, S 33084, WAY 100635, BD 1047 and progesterone) - alone or in combination with pramipexole and fluoxetine or sertraline - changed locomotor activity. The results described in the present paper indicate that co-administration of pramipexole and fluoxetine or sertraline may induce a more pronounced antidepressive activity than does treatment with pramipexole alone, and that in addition to other mechanisms, dopamine D(2/3) and 5-HT(1A) receptors may contribute to the antidepressant-like activity of pramipexole and fluoxetine or sertraline in the forced swimming test in rats

  7. Long Withdrawal of Methylphenidate Induces a Differential Response of the Dopaminergic System and Increases Sensitivity to Cocaine in the Prefrontal Cortex of Spontaneously Hypertensive Rats.

    Directory of Open Access Journals (Sweden)

    Maurício dos Santos Pereira

    Full Text Available Methylphenidate (MPD is one of the most prescribed drugs for alleviating the symptoms of Attention Deficit/Hyperactivity Disorder (ADHD. However, changes in the molecular mechanisms related to MPD withdrawal and susceptibility to consumption of other psychostimulants in normal individuals or individuals with ADHD phenotype are not completely understood. The aims of the present study were: (i to characterize the molecular differences in the prefrontal dopaminergic system of SHR and Wistar strains, (ii to establish the neurochemical consequences of short- (24 hours and long-term (10 days MPD withdrawal after a subchronic treatment (30 days with Ritalin® (Methylphenidate Hydrochloride; 2.5 mg/kg orally, (iii to investigate the dopaminergic synaptic functionality after a cocaine challenge in adult MPD-withdrawn SHR and Wistar rats. Our results indicate that SHR rats present reduced [3H]-Dopamine uptake and cAMP accumulation in the prefrontal cortex (PFC and are not responsive to dopaminergic stimuli in when compared to Wistar rats. After a 24-hour withdrawal of MPD, SHR did not present any alterations in [3H]-Dopamine Uptake, [3H]-SCH 23390 binding and cAMP production; nonetheless, after a 10-day MPD withdrawal, the results showed a significant increase of [3H]-Dopamine uptake, of the quantity of [3H]-SCH 23390 binding sites and of cAMP levels in these animals. Finally, SHR that underwent a 10-day MPD withdrawal and were challenged with cocaine (10 mg/kg i.p. presented reduced [3H]-Dopamine uptake and increased cAMP production. Wistar rats were affected by the 10-day withdrawal of MPD in [3H]-dopamine uptake but not in cAMP accumulation; in addition, cocaine was unable to induce significant modifications in [3H]-dopamine uptake and in cAMP levels after the 10-day withdrawal of MPD. These results indicate a mechanism that could explain the high comorbidity between ADHD adolescent patients under methylphenidate treatment and substance abuse in adult

  8. The incentive amplifying effects of nicotine are reduced by selective and non-selective dopamine antagonists in rats.

    Science.gov (United States)

    Palmatier, Matthew I; Kellicut, Marissa R; Brianna Sheppard, A; Brown, Russell W; Robinson, Donita L

    2014-11-01

    Nicotine is a psychomotor stimulant with 'reinforcement enhancing' effects--the actions of nicotine in the brain increase responding for non-nicotine rewards. We hypothesized that this latter effect of nicotine depends on increased incentive properties of anticipatory cues; consistent with this hypothesis, multiple laboratories have reported that nicotine increases sign tracking, i.e. approach to a conditioned stimulus (CS), in Pavlovian conditioned-approach tasks. Incentive motivation and sign tracking are mediated by mesolimbic dopamine (DA) transmission and nicotine facilitates mesolimbic DA release. Therefore, we hypothesized that the incentive-promoting effects of nicotine would be impaired by DA antagonists. To test this hypothesis, separate groups of rats were injected with nicotine (0.4mg/kg base) or saline prior to Pavlovian conditioning sessions in which a CS (30s illumination of a light or presentation of a lever) was immediately followed by a sweet reward delivered in an adjacent location. Both saline and nicotine pretreated rats exhibited similar levels of conditioned approach to the reward location (goal tracking), but nicotine pretreatment significantly increased approach to the CS (sign tracking), regardless of type (lever or light). The DAD1 antagonist SCH-23390 and the DAD2/3 antagonist eticlopride reduced conditioned approach in all rats, but specifically reduced goal tracking in the saline pretreated rats and sign tracking in the nicotine pretreated rats. The non-selective DA antagonist flupenthixol reduced sign-tracking in nicotine rats at all doses tested; however, only the highest dose of flupenthixol reduced goal tracking in both nicotine and saline groups. The reductions in conditioned approach behavior, especially those by SCH-23390, were dissociated from simple motor suppressant effects of the antagonists. These experiments are the first to investigate the effects of dopaminergic drugs on the facilitation of sign-tracking engendered by

  9. D1 receptors in the nucleus accumbens-shell, but not the core, are involved in mediating ethanol-seeking behavior of alcohol-preferring (P) rats.

    Science.gov (United States)

    Hauser, S R; Deehan, G A; Dhaher, R; Knight, C P; Wilden, J A; McBride, W J; Rodd, Z A

    2015-06-04

    Clinical and preclinical research suggest that activation of the mesolimbic dopamine (DA) system is involved in mediating the rewarding actions of drugs of abuse, as well as promoting drug-seeking behavior. Inhibition of DA D1 receptors in the nucleus accumbens (Acb) can reduce ethanol (EtOH)-seeking behavior of non-selective rats triggered by environmental context. However, to date, there has been no research on the effects of D1 receptor agents on EtOH- seeking behavior of high alcohol-preferring (P) rats following prolonged abstinence. The objective of the present study was to examine the effects of microinjecting the D1 antagonist SCH 23390 or the D1 agonist A-77636 into the Acb shell or Acb core on spontaneous recovery of EtOH-seeking behavior. After 10 weeks of concurrent access to EtOH and water, P rats underwent seven extinction sessions (EtOH and water withheld), followed by 2 weeks in their home cages without access to EtOH or operant sessions. In the 2nd week of the home cage phase, rats were bilaterally implanted with guide cannula aimed at the Acb shell or Acb core; rats were allowed 7d ays to recover before EtOH-seeking was assessed by the Pavlovian Spontaneous Recovery (PSR) model. Administration of SCH23390 (1μg/side) into the Acb shell inhibited responding on the EtOH lever, whereas administration of A-77636 (0.125μg/side) increased responding on the EtOH lever. Microinfusion of D1 receptor agents into the Acb core did not alter responding on the EtOH lever. Responses on the water lever were not altered by any of the treatments. The results suggest that activation of D1 receptors within the Acb shell, but not Acb core, are involved in mediating PSR of EtOH-seeking behavior of P rats. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Evocatin of the Spirit: A-capella-Werke von Gorecki, Pärt, Martin, Barber und Schönberg / Gerhard Pätzig

    Index Scriptorium Estoniae

    Pätzig, Gerhard

    1995-01-01

    Uuest heliplaadist "Evocatin of the Spirit: A-capella-Werke von Gorecki, Pärt, Martin, Barber und Schönberg. Robert Shaw Festival Singers. Robert Shaw (AD: 1994). Telarc/in-akustik CD 80406 (WD: 72'15")

  11. Mar à Vista: Explorando as Estratégias da Familia Schürmann a Bordo de um Veleiro [doi: 10.5329/RECADM.20080702007

    Directory of Open Access Journals (Sweden)

    Antonio Eduardo Husadel

    2008-11-01

    Full Text Available Normal 0 21 false false false PT-BR X-NONE X-NONE MicrosoftInternetExplorer4 RESUMO Novos contornos começaram a ser delineados no campo da estratégia, nas últimas décadas, resultando no surgimento de estudos centrados no entendimento do processo de formação de estratégia à medida em que o mesmo se desenvolve. Mintzberg, Ahlstrand e Lampel (1999 propuseram a analogia da estratégia como um elefante de dez partes, sugerindo que o campo da estratégia é visto por suas partes, o que impossibilita sua reconstituição, pois para entender o todo, é preciso conhecer cada uma das partes que o compõem. Na mesma direção, Vasconcelos (2001 identifica, a partir desses autores, três dimensões da estratégia. Da experiência acumulada em uma circunavegação pelo planeta, o que era, inicialmente, a realização de um sonho, a Familia Schürmann inovou e criou uma empresa com características inconfundíveis, conquistando espaço em um mercado já bastante explorado. Esta pesquisa ancora-se na abordagem interpretativa e tem como objetivo explorar o processo de formação da estratégia, utilizando a experiência da família Schürmann desde sua trajetória na volta ao mundo a bordo de um veleiro. Entrevistas e documentos institucionais foram utilizados como fontes da pesquisa. Como resultado, é apresentado o processo de formação da estratégia da Família Schürmann, evidenciando aspectos de diferentes escolas de pensamento estratégico.   Palavras-Chave Estratégia. Inovação. Aprendizagem. Cultura. Schurmann.     ABSTRACT New contours began to be outlined in the strategy field, in recent decades, resulting in the emergence of studies focused on understanding the process strategy formation on the extent to which it develops. Mintzberg, Ahlstrand & Lampel (1999 proposed the analogy of the elephant as a strategy of ten parties, suggesting that the field of strategy is seen by its parts, which makes their recovery, because to understand the

  12. Qualitative Research in Organizational Studies: Phenomenological Contributions of Alfred Schütz Pesquisa Qualitativa nos Estudos Organizacionais: Contribuições Fenomenológicas de Alfred Schütz

    Directory of Open Access Journals (Sweden)

    Fernando Gomes de Paiva Júnior

    2009-03-01

    Full Text Available Modern science is in crisis. Today, we live in a scientific paradigm transition motivated by differences and complexities. In the organizational field, qualitative research emerges as a methodological alternative to the researcher. It aids the contemporary understanding of the actor involved with the management phenomenon, as it reveals his/her impressions and feelings related to personal and professional lived experiences. The interpretative approach of Alfred Schütz's social phenomenology constitutes one of the variants of the phenomenological movement that makes knowledge of essences possible, and constitutes a type of "intelligible armor" of the organizational being's understanding, which has its structure and specific laws.

  13. The depositional environments of Schöningen 13 II-4 and their archaeological implications.

    Science.gov (United States)

    Stahlschmidt, Mareike C; Miller, Christopher E; Ligouis, Bertrand; Goldberg, Paul; Berna, Francesco; Urban, Brigitte; Conard, Nicholas J

    2015-12-01

    Geoarchaeological research at the Middle Pleistocene site of Schöningen 13 II-4, often referred to as the Speerhorizont, has focused on describing and evaluating the depositional contexts of the well-known wooden spears, butchered horses, and stone tools. These finds were recovered from the transitional contact between a lacustrine marl and an overlying organic mud, originally thought to be a peat that accumulated in place under variable moisture conditions. The original excavators proposed that hominin activity, including hunting and butchery, occurred on a dry lake shore and was followed by a rapid sedimentation of organic deposits that embedded and preserved the artifacts. Our geoarchaeological analysis challenges this model. Here, we present evidence that the sediments of Schöningen 13 II-4 were deposited in a constantly submerged area of a paleolake. Although we cannot exclude the possibility that the artifacts were deposited during a short, extreme drying event, there are no sedimentary features indicative of surface exposure in the sediments. Accordingly, this paper explores three main alternative models of site formation: anthropogenic disposal of materials into the lake, a geological relocation of the artifacts, and hunting or caching on lake-ice. These models have different behavioral ramifications concerning hominin knowledge and exploitation of the landscape and their subsistence strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. From the Pure “We-Relationship” in Schütz to “What Happens Between Us” in Waldenfels: Open Possibilities for an Inclusive Attitude in Relation to the Other

    Directory of Open Access Journals (Sweden)

    Márcio Junglos

    2015-12-01

    Full Text Available This article intends to compare the pure We-relationship in Schütz to what happens between us in Waldenfels. Schütz criticizes Weber’s basic methodological concepts: behavior and rationalism. For Schütz it is impossible through rational observance on relational behavior to guarantee the objectivism of sociology as a science. Schütz tries to prove that only a sociological theory that shows the different realms/worlds from which the interpretation of a product is built, with its obvious limitation of grasping the real meaning, while also clarifying the deep relationship with others, can in fact illustrate its relative anonymity or concreteness. This task involves a sense of searching for concreteness instead of taking for granted its objectiveness. For Waldenfels, the pure We-relationship is too fixed in the subjectivity that is based on one-sided understanding, and decreases possibilities of the event occurring between us. For Schütz, one deals with an eternal paradox of interpretation that will not make us acquainted completely with the other’s mind. The lack of fissure in the We-relationship does not leave space for the possibilities of what happens between us, in other words, the meaning is arrested in subjectivity in an attempt to make meaning as concrete as possible. Waldenfels will not say that the meaning in its integrality can be found, but he will open ways, which lead to a threshold where/elsewhere one will find fissures, new possibilities that first penetrate the body and after can take place in attitudes towards the other.

  15. ANATOMY OF GYNURA AURANTIACA (BLUME SCH.BIP. EX DC. (ASTERACEAE

    Directory of Open Access Journals (Sweden)

    Rodica BERCU

    2014-06-01

    Full Text Available The paper presents a detailed histoanatomical description, of the vegetative organs (root, stem and leaf and photographs as well of Gynura aurantiaca (Blume Sch.Bip. ex DC. It was observed that the root have typical primary dictos structure. The stem has a differentiated in two regions cortex and the stele comprise one ring of open collateral vascular bundles with secondary xylem due to the cambium activity. The petiole anatomy is quite similar in its basic structure with the stem. The blade presents a heterogenous and hypostomatic mesophyll and a number of vascular bundles in the midrib zone. Remarkable is the presence of the filamentous, uniseriate non-glandular hairs in the stem, petiole and leaf blade. The mechanical tissue is present in the stem, petiole and blade as well.

  16. Ciência e tecnologia no Brasil Imperial Guilherme Schüch, Barão de Capanema (1824-1908 Science and technology in Imperial Brazil Guilherme Schüch, Baron of Capanema (1824-1908

    Directory of Open Access Journals (Sweden)

    Silvia Fernanda de Mendonça Figueirôa

    2005-07-01

    Full Text Available O engenheiro e naturalista Guilherme Schüch de Capanema foi, sem dúvida, um expoente da elite Imperial. Circulou por importantes espaços institucionais científicos e técnicos, tendo atuado de forma bastante significativa para a implementação de uma cultura técnico-científica no Brasil e o conseqüente fortalecimento da engenharia e dos engenheiros. Entretanto, Capanema ainda permanece, assim como quase todos os cientistas do Segundo Império, um "desconhecido mal conhecido". O presente trabalho, contudo, não se propõe fazer sua extensa biografia, mas analisar e ressaltar aspectos de sua obra, relacionandoos a sua formação universitária e a sua prática enquanto engenheiro e naturalista.Guilherme Schüch de Capanema was a prominent member of the Brazilian imperial elite. He belonged to several important institutional loci giving his valuable contribution to the implementation of a technical-scientific culture in Brazil, and therefore to the strengthening of both the field of engineering and the engineers. However, Capanema still remains an .unknown not well known., as do the majority of the scientists of the Second Empire. This paper analyzes and stresses aspects of his professional and academic life, related to his university education, and to his practice as engineer and naturalist.

  17. [Henoch-Schönlein Purpura with lung abscess].

    Science.gov (United States)

    Nakazawa, Junji; Watanabe, Atsushi; Nakajima, Tomohiro; Mishina, Taijiro; Miyajima, Masahiro; Higami, Tetsuya

    2013-09-01

    A 72-year-old man had underwent left lower lobectomy for squamous cell carcinoma in our hospital in 2008. Postoperative stage was I A (T1N0M0). In 2010, follow-up chest computed tomography (CT) images showed similar cavitary nodules in segments 2 and 8 of the right lung with positive uptake on fluorodeoxyglucose-positron emission tomography (FDG-PET) images. Physical examination, blood tests, and levels of serum tumor markers showed no abnormality. Transbronchial lung biopsy revealed the absence of malignant cells. Segment 8 of the right lower lobe with the nodule was partially resected, and pathological examination demonstrated lung abscess. He was discharged but was hospitalized in another hospital for purpuric rash, fever, and arthralgia. Microscopic albuminuria was noted, and renal biopsy revealed nephritis with immunoglobulin A( IgA)deposition. He was made a diagnosis of Henoch-Schönlein purpura. Oral steroid therapy( prednisolone 60 mg/d) was initiated, resulting in the improvement of symptoms and disapearance of the cavitary nodule in the right lung segment 2.

  18. Wertigkeit der Schnittbilddiagnostik in der Evaluation des pädiatrischen Schädel-Hirn-Traumas

    OpenAIRE

    Schäffeler, Christoph

    2010-01-01

    Die vorliegende Arbeit untersucht die diagnostische Wertigkeit von Computertomographie (CT) und Magnetresonanztomographie (MRT) in der Diagnostik des pädiatrischen Schädel-Hirn-Traumas. In einer retrospektiven Auswertung der Bildgebung von 64 Patienten im Alter von 0-15 Jahren wurden die Vor- und Nachteile der CT und MRT - Diagnostik bei der Darstellung intrakranieller Traumfolgen herausgearbeitet. Die Ergebnisse räumen der CT weiterhin einen hohen Stellenwert in der Akutdiagnostik ein, zeige...

  19. Anti-alpha-galactosyl antibodies and immune complexes in children with Henoch-Schönlein purpura or IgA nephropathy

    NARCIS (Netherlands)

    Davin, J. C.; Malaise, M.; Foidart, J.; Mahieu, P.

    1987-01-01

    Episodes of hematuria in IgA nephropathy or Henoch-Schönlein purpura are frequently associated with microbial infections. Some of those infectious agents bear alpha-galactosyl residues on their cell surface. These observations prompted us to determine, by passive hemagglutination, the titers of

  20. Muusikamaailm : Milano La Scala sulgeb uksed. Schönberg ja Kandinsky. Preemiaid ja tunnustusi. Witold Szalonek lahkunud. / Priit Kuusk

    Index Scriptorium Estoniae

    Kuusk, Priit, 1938-

    2002-01-01

    Milano La Scala suletakse kaheks aastaks ümberehituseks ja renoveerimiseks. Moskvas toimub näitus ja kontserdisari "Schönberg ja Kandinsky ئ maalikunst ja muusika dialoogis". Erinevaid preemiaid ja tunnustusi saanud muusikad. 74aastasena suri Berliinis nimekas poola helilooja, pianist ja pedagoog Witold Szalonek

  1. EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part I: Overall methodology and clinical characterisation

    DEFF Research Database (Denmark)

    Ruperto, Nicolino; Ozen, Seza; Pistorio, Angela

    2010-01-01

    To report methodology and overall clinical, laboratory and radiographic characteristics for Henoch-Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) classification criteria.......To report methodology and overall clinical, laboratory and radiographic characteristics for Henoch-Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) classification criteria....

  2. Five-year all-cause mortality rates across five categories of substantiated elder abuse occurring in the community.

    Science.gov (United States)

    Burnett, Jason; Jackson, Shelly L; Sinha, Arup K; Aschenbrenner, Andrew R; Murphy, Kathleen Pace; Xia, Rui; Diamond, Pamela M

    2016-01-01

    Elder abuse increases the likelihood of early mortality, but little is known regarding which types of abuse may be resulting in the greatest mortality risk. This study included N = 1,670 cases of substantiated elder abuse and estimated the 5-year all-cause mortality for five types of elder abuse (caregiver neglect, physical abuse, emotional abuse, financial exploitation, and polyvictimization). Statistically significant differences in 5-year mortality risks were found between abuse types and across gender. Caregiver neglect and financial exploitation had the lowest survival rates, underscoring the value of considering the long-term consequences associated with different forms of abuse. Likewise, mortality differences between genders and abuse types indicate the need to consider this interaction in elder abuse case investigations and responses. Further mortality studies are needed in this population to better understand these patterns and implications for public health and clinical management of community-dwelling elder abuse victims.

  3. Paleoenvironment and possibilities of plant exploitation in the Middle Pleistocene of Schöningen (Germany). Insights from botanical macro-remains and pollen.

    Science.gov (United States)

    Bigga, Gerlinde; Schoch, Werner H; Urban, Brigitte

    2015-12-01

    Plant use is an elusive issue in Paleolithic archaeology. Due to poor organic preservation in many sites, botanical material is not always present. The sediments in Schöningen, however, contain abundant botanical macro-remains like wood, fruits, seeds, and other parts of plants which offer the opportunity to reconstruct the local vegetation. Combined with palynological results, it is possible to reveal the full potential of this environment to hominins. Ethnobotanical studies of hunter-gatherer societies living in similar environments illustrate the importance of plants for subsistence purposes. The identified taxa from the archaeological horizons at Schöningen include a broad spectrum of potentially exploitable species that could be sources of food, raw material, and firewood. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. ["Reasonable cause"--an undefined legal term for the justification of the killing of equids].

    Science.gov (United States)

    Deegen, E

    2008-03-01

    Killing of a vertebrate animal in Germany is allowed or not punishable only if a "reasonable cause" can be identified (Article 17 No. 1 TierSchG). A legal definition of the term "reasonable cause" does not exist. Currently the following definitions of the "reasonable cause" for the killing of equids are accepted: 1. Slaughter (in accordance with the equid pass and waiting periods) reasonable cause: Food production, initiated by the owner's desire. The requirements for slaughter of a sick animal or an emergency slaughter are defined through EU-legislations. 2. Euthanasia (in its original meaning) Reasonable cause: a) Compassion, initiated through medical indication b) scientific purposes (experimental animals) initiated through governmental authorization of a research request c) Epidemiological reasons initiated through veterinary legislative measures. According to the law for the protection of animals (TierSchG) "non curable pain or suffering" is a prerequisite for the killing of an animal because of a medical indication. Presuming an adequate knowledge base of the veterinarian this should leave enough room for an adequate medically reasoned decision. However, both a faulty veterinary explanation of a reasonable cause and an undue delay of the euthanasia (follow Article 17) can lead to an illegal punishable act (severe pain or suffering). Examples of veterinary medical indications for euthanasia will be presented. In addition, the question whether euthanasia can be considered as an alternative to treatment will be discussed. Finally, the more restrictive interpretations of the "reasonable cause" put forth by insurance companies will be explained. Future higher court decisions should lead to an adaptation of the insurance companies' interpretations of the "reasonable cause" to the outline presented above.

  5. Soil and phytosociological characterization of an area with predominance of arnica (Lychnophora pohlii sch. bip.

    Directory of Open Access Journals (Sweden)

    André Rodrigues da Cunha Gianotti

    2013-06-01

    Full Text Available Lychnophora pohlii Sch. Bip. (Asteraceae, known as "Arnica mineira", is widely used in folk medicine and very abundant in the altitude vegetation of rocky grassland. The aim of this work was to study the density of this species and its relationship with soil parameters in rocky grassland in Diamantina, in the Upper Jequitinhonha region, Minas Gerais. Ten contiguous 20 x 50 m plots were marked (total sampled area 10,000 m² on the campus Juscelino Kubitschek of the Federal University of Jequitinhonha and Mucuri Valleys (UFVJM. The plants in these plots were evaluated for frequency, dominance and density. The relationship between the density of this species with nine soil physical and chemical properties was analyzed by means of canonical correspondence analysis (CCA. The highest plant abundance (I of the species Lychnophora pohlii Sch. Bip. was found in the vegetation sampling areas: plot 6 with 255 plants, plot 7 with 173, plot 8 with 189, plot 9 with 159, and plot 1 with 151 plants. In these areas, the floristic soil characteristics were similar, resulting in spatial proximity in the ACC diagrams. The density of Lychnophora pohlii was higher in plots with higher pH, P-rem and base saturation, the variables most strongly correlated with the first axis of canonical correspondence analysis.

  6. Annette Geiger (Hg.: Der schöne Körper. Köln u.a.: Böhlau Verlag 2008

    Directory of Open Access Journals (Sweden)

    Susanne Gramatzki

    2009-07-01

    Full Text Available In den Beiträgen des Bandes werden unterschiedlichste Formen des Schönheitshandelns in Vergangenheit und Gegenwart unter einer kulturwissenschaftlichen Perspektive beleuchtet. Modische Kleidung, dekorative Kosmetik, Diäten, Figurtraining, Schönheitsoperationen usw. stehen dem Ich als Techniken zur Verfügung, um einem idealen, häufig über die Medien vermittelten Körperbild nahezukommen. Der instruktive und angemessen bebilderte Band betrachtet diese Körperpraktiken als gleichermaßen gesellschaftliche wie ästhetische Phänomene; Zwang und Lust der Simulation werden von den Autor/-innen ebenso behandelt wie das Verhältnis von (Geschlechter-Identität und (Geschlechter-Performanz.The essays in this volume illuminate the most diverse forms of past and present acts of beauty from the perspective of Cultural Studies. Fashionable clothing, decorative cosmetics, diets, body sculpting, cosmetic operations, etc. are available to the individual as techniques to achieve the ideal body image that is often communicated through the media. The instructive and appropriately illustrated volume sees these body practices as both social and aesthetic phenomena. The authors address compulsion, the desire for simulation, and the relationship between (gender identity and (gender performance.

  7. [Henoch-Schönlein purpura in the adult].

    Science.gov (United States)

    Pillebout, E; Verine, J

    2014-06-01

    Henoch-Schönlein purpura is a systemic vasculitis of the small vessels characterized by perivascular leucocyte infiltrates. It is an immunoglobulin A-related immune complex-mediated disease involving the skin, the joints and the gastrointestinal system. Renal disease may sometimes be associated to these clinical manifestations. Prevalence of the nephritis is highly variable, depending on the series. More rarely, other organs such as the lungs, the heart or the nervous system may be involved. The clinical diagnosis is confirmed by histopathology of the skin (leukocytoclastic vasculitis) and kidney (endo-capillary proliferative glomerulonephritis), showing IgA deposits in these tissues. Short-term prognosis depends on the severity of digestive involvement, but long-term prognosis depends on the renal disease. Recent publications of pediatric and adult series show that the chronic renal failure may progress, sometimes more than ten years after the initial flare. Treatment is usually supportive. The benefit of more specific treatments (corticosteroids or immunosuppressive drugs) in severe visceral forms (usually abdominal or kidney) has not yet been established. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  8. Clinical outcomes in children with Henoch-Schönlein purpura nephritis without crescents.

    Science.gov (United States)

    Delbet, Jean Daniel; Hogan, Julien; Aoun, Bilal; Stoica, Iulia; Salomon, Rémi; Decramer, Stéphane; Brocheriou, Isabelle; Deschênes, Georges; Ulinski, Tim

    2017-07-01

    Henoch-Schönlein purpura is the most common vasculitis in children. Its long-term prognosis depends on renal involvement. The management of Henoch-Schönlein purpura nephritis (HSPN) remains controversial. This study reports the prognosis of children with HSPN presenting with class 2 International Study of Kidney Disease in Children (ISKDC) nephritis. All children with HSPN class 2 diagnosed between 1995 and 2015 in four pediatric nephrology centers were included, and clinical and biological data were collected from the medical files. The primary endpoint was proteinuria remission defined as a proteinuria 3 g/L, 52% proteinuria between 1 and 3 g/L, and 18% proteinuria <1 g/L. Forty-seven percent of patients received orally treatment with steroids alone, 37% received methylprednisolone pulses followed by steroids orally, 18% received no steroids. Although 85% reached remission during follow-up, 12% did not maintain complete remission over time so that only 75% remained in complete remission by the end of the follow-up. Univariate analysis found a higher likelihood of remission in patients with higher proteinuria at disease onset (p = 0.009). This trend was not found in the multivariate analysis after adjusting for treatments, as patients with higher proteinuria were most often treated with steroids. Our study shows that one fourth of patients with HSPN class 2 remain proteinuric and thus carry the risk of developing chronic kidney disease over the long term. This finding, together with the better outcome of patients treated with steroids, is in favor of using high-dose steroids orally or IV in these patients.

  9. Imatinib treatment causes substantial transcriptional changes in adult Schistosoma mansoni in vitro exhibiting pleiotropic effects.

    Directory of Open Access Journals (Sweden)

    Christin Buro

    2014-06-01

    Full Text Available Schistosome parasites cause schistosomiasis, one of the most important infectious diseases worldwide. For decades Praziquantel (PZQ is the only drug widely used for controlling schistosomiasis. The absence of a vaccine and fear of PZQ resistance have motivated the search for alternatives. Studies on protein kinases (PKs demonstrated their importance for diverse physiological processes in schistosomes. Among others two Abl tyrosine kinases, SmAbl1 and SmAbl2, were identified in Schistosoma mansoni and shown to be transcribed in the gonads and the gastrodermis. SmAbl1 activity was blocked by Imatinib, a known Abl-TK inhibitor used in human cancer therapy (Gleevec/Glivec. Imatinib exhibited dramatic effects on the morphology and physiology of adult schistosomes in vitro causing the death of the parasites.Here we show modeling data supporting the targeting of SmAbl1/2 by Imatinib. A biochemical assay confirmed that SmAbl2 activity is also inhibited by Imatinib. Microarray analyses and qRT-PCR experiments were done to unravel transcriptional processes influenced by Imatinib in adult schistosomes in vitro demonstrating a wide influence on worm physiology. Surface-, muscle-, gut and gonad-associated processes were affected as evidenced by the differential transcription of e.g. the gynecophoral canal protein gene GCP, paramyosin, titin, hemoglobinase, and cathepsins. Furthermore, transcript levels of VAL-7 and egg formation-associated genes such as tyrosinase 1, p14, and fs800-like were affected as well as those of signaling genes including a ribosomal protein S6 kinase and a glutamate receptor. Finally, a comparative in silico analysis of the obtained microarray data sets and previous data analyzing the effect of a TGFβR1 inhibitor on transcription provided first evidence for an association of TGFβ and Abl kinase signaling. Among others GCP and egg formation-associated genes were identified as common targets.The data affirm broad negative effects of

  10. Muusikamaailm : Lahkumiskingitus Udo Zimmermannile. Haitinki esimene "Tristan ja Isolde". Uusooper Garcia Lorca järgi. Schönbergi esietendus Viinis (!) / Priit Kuusk

    Index Scriptorium Estoniae

    Kuusk, Priit, 1938-

    2000-01-01

    U. Zimmermann lahkub Leipzigi Ooperi juhi ja dirigendi kohalt ja asub Deutsche Operi etteotsa Berliinis. B. Haitink juhatab Londoni Kuninglikus Ooperis esmakordselt "Tristani ja Isolde" etendust. A. Reimanni uusooperist "Bernarda Alba maja". A. Schönbergi oratooriumi "Jakobsleiter" esietendusest Viini Riigiooperis

  11. Adolescent social defeat alters markers of adult dopaminergic function.

    Science.gov (United States)

    Novick, Andrew M; Forster, Gina L; Tejani-Butt, Shanaz M; Watt, Michael J

    2011-08-10

    Stressful experiences during adolescence can alter the trajectory of neural development and contribute to psychiatric disorders in adulthood. We previously demonstrated that adolescent male rats exposed to repeated social defeat stress show changes in mesocorticolimbic dopamine content both at baseline and in response to amphetamine when tested in adulthood. In the present study we examined whether markers of adult dopamine function are also compromised by adolescent experience of social defeat. Given that the dopamine transporter as well as dopamine D1 receptors act as regulators of psychostimulant action, are stress sensitive and undergo changes during adolescence, quantitative autoradiography was used to measure [(3)H]-GBR12935 binding to the dopamine transporter and [(3)H]-SCH23390 binding to dopamine D1 receptors, respectively. Our results indicate that social defeat during adolescence led to higher dopamine transporter binding in the infralimbic region of the medial prefrontal cortex and higher dopamine D1 receptor binding in the caudate putamen, while other brain regions analyzed were comparable to controls. Thus it appears that social defeat during adolescence causes specific changes to the adult dopamine system, which may contribute to behavioral alterations and increased drug seeking. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Michael Jäckel, Julia Derra, Cornelia Eck: SchönheitsAnsichten. Geschlechterbilder in Werbeanzeigen und ihre Bewertung. Baden-Baden: Nomos Verlag 2009.

    Directory of Open Access Journals (Sweden)

    Waltraud Posch

    2010-11-01

    Full Text Available Michael Jäckel, Julia Derra, and Cornelia Eck’s cross-generational study answers the question as to which concepts of beauty are presented in magazine advertisements and how recipients react to these concepts. The book provides an important basis for Media Studies and Gender Sociology particularly because it also shows medial constructions of gender that are initially invisible and because it shows gender related illustrations of physicality and beauty.In einer generationenübergreifenden Studie gehen Michael Jäckel, Julia Derra und Cornelia Eck der Frage nach, welche Schönheitsbilder in der Zeitschriftenwerbung präsentiert und wie diese von Rezipient/-innen aufgenommen werden. Das Buch liefert eine wichtige Basis für Medienforschung und Soziologie der Geschlechter, zumal es auch vordergründig nicht sichtbare mediale Konstruktionen von Geschlecht und die geschlechtsbezogene Darstellung von Körperlichkeit und Schönheit aufzeigt.

  13. Involvement of dopamine receptors within the dorsal hippocampus in suppression of the formalin-induced orofacial pain.

    Science.gov (United States)

    Shamsizadeh, Ali; Pahlevani, Pouyan; Haghparast, Amir; Moslehi, Maryam; Zarepour, Leila; Haghparast, Abbas

    2013-12-01

    It is widely established that the dopaminergic system has profound effects on pain modulation in different regions of the brain including the hippocampus, the salient area for brain functions. The orofacial region is one of the most densely innervated (by the trigeminal nerves) areas of the body susceptible to acute and chronic pains. In this study, we tried to examine the effects of dopamine receptors located in the dorsal hippocampus (CA1) region upon the modulation of orofacial pain induced by the formalin test. To induce orofacial pain in male Wistar rats, 50μl of 1% formalin was subcutaneously injected into the upper lip. In control and experimental groups, two guide cannulae were stereotaxically implanted in the CA1, and SKF-38393 (0.25, 0.5, 1 and 2μg/0.5μl saline) as a D1-like receptor agonist, SCH-23390 (1μg/0.5μl saline) as a D1-like receptor antagonist, Quinpirole (0.5, 1, 2 and 4μg/0.5μl saline) as a D2-like receptor agonist and Sulpiride(3μg/0.5μl DMSO) as a D2-like receptor antagonist or vehicles were microinjected. For induction of orofacial pain, 50μl of 1% formalin was subcutaneously injected into the left side of the upper lip. Results indicated that SKF-38393 at the dose of 1 and 2μg significantly reduced pain during the first and second phases of observed pain while SCH-23390 reversed such analgesic effect. Moreover, there is a significant difference between groups in which animals received 2 and 4μg quinpirole or vehicle in the first phase (early phase) of pain. The three high doses of this compound (1, 2 and 4μg) appeared to have an analgesic effect during the second (late) phase. Furthermore, Sulpiride could potentially reverse the observed analgesic effects already induced by an agonist. Current findings suggest that the dorsal hippocampal dopamine receptors exert an analgesic effect during the orofacial pain test. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Palladium-catalyzed heteroannulation approach to 7-azatryptophan with a Schöllkopf chiral auxiliary

    Energy Technology Data Exchange (ETDEWEB)

    Gee, Moon Bae; Kim, Tae Seung; Yun, Eul Kgun [Dept. of Chemistry, Chungnam National University, Daejeon (Korea, Republic of)

    2015-05-15

    Our previous results on heteroannulation with unprotected 2-amino-3-iodopyridine and internal alkynes showed very low yields of the annulated product. The synthetic limitation could be due to the low nucleophilicity of the nitrogen that exists in the three tautomeric forms of 2-amino-pyridine (Scheme 1) or to the easy formation of a palladium complex with 2-aminopyridine. First, we examined the synthesis of the azaindole precursor, followed by reaction with a Schöllkopf chiral auxiliary. The heteroannulation provided the desired annulated product 5 in 60% yield, along with an uncyclized Sonogawasihra coupling product. After purifying product 5 by column chromatography, it was converted to 7-aza-tryptophan.

  15. Vergleich verschiedener Beurteilungsverfahren an Röntgenbildern des Ellbogengelenkes beim Deutschen Schäferhund und Rottweiler unter Berücksichtigung des Einflusses der Lagerung als Basis einer züchterischen Selektion gegen die Ellbogengelenksdysplasie

    OpenAIRE

    Klein, Sandra

    2010-01-01

    Ziel dieser Untersuchung war es, drei Bewertungsverfahren zur Beurteilung der Ellbogengelenksdysplasie bei Hunden der Rasse Deutscher Schäferhund und Rottweiler miteinander zu vergleichen. Hierbei sollte insbesondere ein Einfluss der Lagerung während der Röntgenaufnahme überprüft werden. Bewertet wurden Röntgenaufnahmen von 19.798 Deutschen Schäferhunden und 2.430 Rottweiler, von denen bereits ein offizieller ED – Befund vorlag. Es erfolgte eine Beurteilung entsprechend der zwei Punktesch...

  16. Púrpura de Henoch-Schönlein com acometimento incomum de face Unusual face involvement in Henoch-Schönlein purpura

    Directory of Open Access Journals (Sweden)

    Carolina Bassoli de Azevedo

    2009-12-01

    Full Text Available A Púrpura de Henoch-Shönlein é uma vasculite de causa idiopática, que se caracteriza pelo depósito predominante de IgA na parede dos pequenos vasos, envolvendo tipicamente pele, intestino, articulações e glomérulo renal. O acometimento cutâneo ocorre principalmente em membros inferiores e região glútea, sendo raramente encontrado em face e membros superiores. Relatamos o caso de uma paciente do sexo feminino, com seis anos de idade, que apresentava lesões púrpuricas em região auricular, periorbital, malar, mentoniana e membros superiores, além de artralgia e volvo intestinal. Após tratamento cirúrgico e pulsoterapia com glicocorticoide, houve regressão dos sintomas, sem maiores complicações.Henoch-Schönlein Purpura is an idiopathic vasculitis characterized by deposits of immunoglobulin, mainly IgA, on the walls of small vessels, typically involving the skin, gut, joints, and renal glomeruli. Cutaneous involvement affects specially the lower limbs and buttocks, and it is seldom found on the face and upper limbs. We report the case of a 6-year old girl with purpuric lesions over the auricular, periorbital, malar, and mentonian regions and the upper limbs, arthralgia, and intestinal torsion. After surgical treatment and pulse therapy with glucocorticoids, her symptoms subsided without further complications.

  17. Henoch-Schönlein purpura nephritis occurring postpartum in a patient with anti-PL-7 anti-synthetase syndrome.

    Science.gov (United States)

    Nagai, Kojiro; Kishi, Jun; Morizumi, Shun; Minakuchi, Jun; Bando, Yoshimi; Nishioka, Yasuhiko; Doi, Toshio

    2017-09-01

    A 37-year-old pregnant woman developed purpura which was subsequently diagnosed as Henoch-Schönlein purpura (HSP). After childbirth, the patient developed proteinuria and hematuria. Further examination revealed that the HSP nephritis (HSPN) was associated with anti-threonyl-tRNA synthetase anti-synthetase syndrome. The onset of HSPN during pregnancy or after childbirth is rare. Moreover, to our knowledge, this is the first case to describe renal involvement in anti-synthetase syndrome.

  18. High Prevalence of Sinusitis in Children with Henoch-Schönlein Purpura

    Directory of Open Access Journals (Sweden)

    Haruna Nakaseko

    2011-01-01

    Full Text Available We evaluated the prevalence and the types of infectious foci in oral as well as ear, nose, and throat diseases, and we examined incidence of renal involvement with active treatment for focal infection in children with Henoch-Schönlein Purpura. A total of 96 children who presented at Aichi Children's Health and Medical Center and were diagnosed as having HSP were evaluated for infectious foci in the ear, nose, throat, and oral cavities. Seventy-one of 96 children (74.0% had some type of infectious lesion, such as sinusitis or tonsillitis, and the prevalence of sinusitis was the highest (51 cases, 53.7%. In 44 HSP patients without renal involvement at the first examination, the incidence of nephritis was lower (13.6% than in previous reports (17–54% due to our aggressive intervention for infectious foci.

  19. Henoch–Schönlein purpura: a clinical case with dramatic presentation

    Science.gov (United States)

    Bento, João; Magalhães, Adriana; Moura, Conceição Souto; Hespanhol, Venceslau

    2010-01-01

    A case study involving a 55-year-old Caucasian male with end-stage glomerulosclerosis is presented here. Kidney biopsies showed no deposits on imunofluorescent microscopy. Relapsing massive haemoptysis and suspected bronchovascular malformation required lung lobectomy which revealed malformative and tortuous small blood vessels, with no vasculitis. Blood antinuclear antibodies, antineutrophil cytoplasmic antibodies and antiglomerular basement membrane antibodies were undetectable. Seric immunoglobulins and complement levels were normal. Three months later, arthralgia and joint oedema first appeared. Skin biopsy revealed vasculitis immune-reactive to immunoglobulin A. Systemic corticotherapy was then started. Two weeks later, the patient presented with abdominal pain melena and rectal bleeding (haematoquesia). Endoscopic study showed diffuse gastrointestinal haemorrhage. Angiographic study revealed diffuse lesions compatible with vasculitis and haemorrhage from multiple spots. Cyclophosphamide and then intravenous immunoglobulin were associated to treatment without response. Increasing blood loss occurred, with massive gastrointestinal haemorrhage and haemorrhagic ascitis. Death occurred due to uncontrolled diffuse bleeding. Necropsy findings showed generalised small vessels vasculitis compatible with Henoch–Schönlein purpura. PMID:22778211

  20. Severe Henoch-Schönlein purpura with infliximab for ulcerative colitis.

    Science.gov (United States)

    Song, Yang; Shi, Yan-Hong; He, Chong; Liu, Chang-Qin; Wang, Jun-Shan; Zhao, Yu-Jie; Guo, Yan-Min; Wu, Rui-Jin; Feng, Xiao-Yue; Liu, Zhan-Ju

    2015-05-21

    Infliximab (IFX) is an anti-tumor necrosis factor chimeric antibody that is effective for treatment of autoimmune disorders such as Crohn's disease and ulcerative colitis (UC). IFX is well tolerated with a low incidence of adverse effects such as infections, skin reactions, autoimmunity, and malignancy. Dermatological manifestations can appear as infusion reaction, vasculitis, cutaneous infections, psoriasis, eczema, and skin cancer. Here, we present an unusual case of extensive and sporadic subcutaneous ecchymosis in a 69-year-old woman with severe UC, partial colectomy and cecostomy, following her initial dose of IFX. The reaction occurred during infliximab infusion, and withdrawal of IFX led to gradual alleviation of her symptoms. We concluded that Henoch-Schönlein purpura, a kind of leukocytoclastic vasculitis, might have contributed to the development of the bruising. Although the precise mechanisms of the vasculitis are still controversial, such a case highlights the importance of subcutaneous adverse effects in the management of UC with IFX.

  1. Chinese herbal medicine for the treatment of Henoch-Schönlein purpura nephritis in children: A prospective cohort study protocol.

    Science.gov (United States)

    Zhang, Jun; Lv, Jing; Pang, Shuang; Bai, Xiaohong; Yuan, Fang; Wu, Yubin; Jiang, Hong; Yang, Guanqi; Zhang, Shaoqing

    2018-06-01

    Henoch-Schönlein purpura nephritis (HSPN) involves the renal impairment of Henoch-Schönlein purpura and can easily relapse into life-threatening late nephropathy in severe cases. Although there is a lack of validated evidence for its effectiveness, Chinese herbal medicine (CHM) is one of the most commonly used methods in China to treat HSPN. It is thus need to report the protocol of a prospective cohort trial using CHM to investigate the effectiveness, safety and advantages for children with HSPN. This large, prospective, multicenter cohort study started in May 2015 in Shenyang. Six hundred children diagnosed with HSPN were recruited from 3 institutions and are followed-up every 2 to 4 weeks till May 2020. Detailed information of participants includes general information, history of treatment, physical examination, and symptoms of TCM is taken face-to-face at baseline. This study has received ethical approval from the ethics committee of institutional review board of the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine (No.2016CS(KT)-002-01). Articles summarizing the primary results and ancillary analyses will be published in peer-reviewed journals. Clinical Trials Registration: NCT02878018.

  2. EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria

    DEFF Research Database (Denmark)

    Ozen, Seza; Pistorio, Angela; Iusan, Silvia M

    2010-01-01

    To validate the previously proposed classification criteria for Henoch-Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA)....

  3. Relevance in print of law of administrative regulations according to paragraph 48 BImSchG in the licensing procedure

    International Nuclear Information System (INIS)

    Breuer, R.

    1978-01-01

    The author discusses in great detail the legal problem of administrative regulations according to paragraph 48 of the Bundes-Immissionsschutzgesetz, BImSchG (Federal Act for the prevention of immissions) and their relevance in point of law in licensing procedures. He very carefully and skilfully presents the different opinions stated in the precedents and by the body of doctrine and quite convincingly explains why he rejects the doctrine of allowing the administration some latitude in their judgement, and thus the doctrine of the defensible opinion with regard to the examination by the court of undefined legal terms. According to the auther's view, the administrative regulations should be regarded as anticipated expert opinions because of the way they are drawn up and because of the way the relevant committees setting up the rules are constituted, i.e. they can serve as a basis for judical decisions. In this connection the author points out that in any case it is left to the court's decisions whether a non-formal expert opinion is deemed to be sufficient, or whether the rules of procedure require a formal expert opinion. Furthermore, several ways of enhancing the binding effect of the administrative regulations pursuant to paragraph 48 of the BImSchG by means of legislatory measures are shown. (UN) [de

  4. Differential effects of dopamine antagonists infused to the medial preoptic area on the sexual behavior of female rats primed with estrogen and progesterone.

    Science.gov (United States)

    Graham, M Dean; Pfaus, James G

    2012-10-01

    Dopamine (DA) in the medial preoptic area (mPOA) is important for the control of appetitive aspects of sexual behavior in the female rat. Recently, following infusions of DA agonists to the mPOA of females primed with estradiol benzoate (EB) alone, we found that the ratio of D1R/D2R activity within the mPOA determines the expression of appetitive behaviors (Graham and Pfaus, 2010). To further the knowledge of this mechanism, the present experiments examined the effects of intra-mPOA infusions of selective DA receptor antagonists. Ovariectomized, sexually-experienced rats primed with EB and progesterone (P) were implanted bilaterally with cannulae aimed at the mPOA and infused with 4 doses (0, 0.25, 1.0 and 4.0 μg) of the nonselective D1R/D2R antagonist flupenthixol (FLU), and selective D1R or D2R antagonists, SCH 23390 (SCH) or raclopride (RAC), respectively, in a randomized order prior to tests of sexual behavior in bilevel chambers. The high dose of FLU significantly decreased solicitations, hops and darts, and pacing behavior. The high dose of SCH also significantly decreased solicitations. In contrast, the high dose of RAC produced an increase in pacing, and a trend toward an increase in solicitations but no other effect on sexual behavior. These results reinforce the idea that the ratio of D1R/D2R activity within the mPOA of female rats is critical for the expression of appetitive behaviors, and further that this ratio is altered by P which shifts the DA effect to a predominantly facilitative D1R activation. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Transformation of Au144(SCH2CH2Ph)60 to Au133(SPh-tBu)52 Nanomolecules: Theoretical and Experimental Study.

    Science.gov (United States)

    Nimmala, Praneeth Reddy; Theivendran, Shevanuja; Barcaro, Giovanni; Sementa, Luca; Kumara, Chanaka; Jupally, Vijay Reddy; Apra, Edoardo; Stener, Mauro; Fortunelli, Alessandro; Dass, Amala

    2015-06-04

    Ultrastable gold nanomolecule Au144(SCH2CH2Ph)60 upon etching with excess tert-butylbenzenethiol undergoes a core-size conversion and compositional change to form an entirely new core of Au133(SPh-tBu)52. This conversion was studied using high-resolution electrospray mass spectrometry which shows that the core size conversion is initiated after 22 ligand exchanges, suggesting a relatively high stability of the Au144(SCH2CH2Ph)38(SPh-tBu)22 intermediate. The Au144 → Au133 core size conversion is surprisingly different from the Au144 → Au99 core conversion reported in the case of thiophenol, -SPh. Theoretical analysis and ab initio molecular dynamics simulations show that rigid p-tBu groups play a crucial role by reducing the cluster structural freedom, and protecting the cluster from adsorption of exogenous and reactive species, thus rationalizing the kinetic factors that stabilize the Au133 core size. This 144-atom to 133-atom nanomolecule's compositional change is reflected in optical spectroscopy and electrochemistry.

  6. Heat stress causes substantial labour productivity loss in Australia

    Science.gov (United States)

    Zander, Kerstin K.; Botzen, Wouter J. W.; Oppermann, Elspeth; Kjellstrom, Tord; Garnett, Stephen T.

    2015-07-01

    Heat stress at the workplace is an occupational health hazard that reduces labour productivity. Assessment of productivity loss resulting from climate change has so far been based on physiological models of heat exposure. These models suggest productivity may decrease by 11-27% by 2080 in hot regions such as Asia and the Caribbean, and globally by up to 20% in hot months by 2050. Using an approach derived from health economics, we describe self-reported estimates of work absenteeism and reductions in work performance caused by heat in Australia during 2013/2014. We found that the annual costs were US$655 per person across a representative sample of 1,726 employed Australians. This represents an annual economic burden of around US$6.2 billion (95% CI: 5.2-7.3 billion) for the Australian workforce. This amounts to 0.33 to 0.47% of Australia’s GDP. Although this was a period when many Australians experienced what is at present considered exceptional heat, our results suggest that adaptation measures to reduce heat effects should be adopted widely if severe economic impacts from labour productivity loss are to be avoided if heat waves become as frequent as predicted.

  7. An adult patient with Henoch-Schönlein purpura and non-occlusive mesenteric ischemia

    Science.gov (United States)

    2013-01-01

    Background Onset of Henoch-Schönlein purpura (HSP) in middle age is uncommon, and adults with renal or gastrointestinal involvement present with more severe disease than do similar pediatric patients. Case presentation We present the case of a 69-year-old male with HSP who, after treatment with steroids, cyclophosphamide, and continuous intravenous prostaglandin E1 (PGE1), died as a result of severe gastrointestinal involvement with non-occlusive mesenteric ischemia (NOMI). Vascular narrowing associated with the NOMI improved after catheter injection of PGE1 and prednisolone, but the patient died of bleeding from an exposed small vessel. At autopsy there was no active vasculitis in the jejunal submucosa. Conclusion Treatment with PGE1 and prednisolone might improve small-vessel vasculitis associated with NOMI. PMID:23343144

  8. Messung computer- und informationsbezogener Kompetenzen von Schülerinnen und Schülern als Schlüsselkompetenz im 21. Jahrhundert

    Directory of Open Access Journals (Sweden)

    Birgit Eickelmann

    2011-12-01

    Full Text Available Mit der ICILS 2013 (International Computer and Information Literacy Study realisiert die IEA (International Association for the Evaluation of Educational Achievement erstmalig eine internationale Vergleichsstudie, die empirisch abgesichert Schülerkompetenzen im Bereich der computer- und informationsbezogenen Kompetenzen (Computer and Information Literacy, kurz: CIL erhebt. Mit dieser Studie werden informations- und computerbezogene Kompetenzen, die im 'deutschen' Sprachgebrauch auch oft unter dem affinen Begriff ICT-Literacy geführt werden, als Large-Scale-Assessments erfasst. Im folgenden Beitrag soll die Relevanz der Messung dieser Schlüsselkompetenz aufgezeigt werden. Alsdann werden das der Studie zugrundeliegende Messkonstrukt und seine definitorischen Bereiche beschrieben. Die hier vorgestellte Definition des CIL-Konstruktes bildet die Grundlage für die datengestützte Entwicklung von Kompetenzstufen, die aus der Hauptstudie von ICILS im Jahr 2013 hervorgehen werden. The IEA (International Association for the Evaluation of Educational Achievement will realize with ICILS 2013 (International Computer and Information Literacy Study for the first time an international comparative study, which will provide evidence about students' computer- and information-related competencies across countries. As a large-scaleassessment, the study examines the outcome of computer and information literacy. This article outlines the challenges and the relevance of the measurement of this core competence. Additionally the theoretical assessment constructs of CIL (computer and information literacy and their definitional scopes are explained in more detail. The presented definition of CIL is the foundation for a data-based development of proficiency levels within the study, which main survey will take place in 2013.

  9. IgA nephropathy and Henoch-Schönlein nephritis in adults : with special reference to factors affecting outcome

    OpenAIRE

    Rauta, Virpi

    2006-01-01

    IgA nephropathy (IgAN) is the most common primary glomerulonephritis. In one third of the patients the disease progresses, and they eventually need renal replacement therapy. IgAN is in most cases a slowly progressing disease, and the prediction of progression has been difficult, and the results of studies have been conflicting. Henoch-Schönlein nephritis (HSN) is rare in adults, and prediction of the outcome is even more difficult than in IgAN. This study was conducted to evaluate the c...

  10. Kinetostatic and Inertial Conditioning of the McGill Schönflies-Motion Generator

    Directory of Open Access Journals (Sweden)

    Alessandro Cammarata

    2010-01-01

    Full Text Available This paper focuses on the optimization of the McGill Schönflies Motion Generator. Recent trends on optimum design of parallel robots led us to investigate the advantages and disadvantages derived from an optimization based on performance indices. Particularly, we optimize here two different indices: the kinematic conditioning and the inertial conditioning, pertaining to the condition number of the Jacobian matrix and to that of the generalized inertia matrix of the robot, respectively. The problem of finding the characteristic length for the robot is first investigated by means of a constrained optimization problem; then plots of the kinetostatic and the inertial conditioning indices are provided for a particular trajectory to be tracked by the moving platform of the SMG. Deep connections appear between the two indices, reflecting a correlation between kinematics and dynamics.

  11. Irradiation inactivation studies of the dopamine D1 receptor and dopamine-stimulated adenylate cyclase in rat striatum

    International Nuclear Information System (INIS)

    Anderson, P.H.; Nielson, M.

    1987-01-01

    In frozen rat striatal tissue, exposed to 10 MeV electrons from a linear accelerator, the sizes of the dopamine (DA) D 1 receptor and the DA sensitive adenylate cyclase complex were determined using target size analysis. The number of D 1 receptors (labelled by [ 3 H]SCH 23390)declined monoexponentially with increasing radiation intensity, yielding a molecular weight (mol. wt.) of 80kDa. Also the activity of the catalytic unit (C) of the adenylate cyclase (as measured by forskolin stimulation), decreased monoexponentially however with a mol. wt. of 145 kDa. Both basal, DA- and flouride (F - ) stimulated activity declined in a concave downward fashion with a limiting mol. wt. of 134, 138 and 228 kDa respectively. It was estimated that the basal and DA - stimulated activity originated from an enzyme complex with a mol. wt. of 325 kDa a value close to the combined size of R G S + C. These data suggest that F - stimulation of the adenylate cyclase, which occurs by a G S activation, does not cause disassociation of G S into the α S and βγ subunits. Further, the AA-regulated adenylate cyclase apparently exists as a complex consisting of RG S and C; the mechanisms of hormonal activation is dissociation of C from this complex

  12. Corticosteroid therapy in Henoch-Schönlein gastritis

    Directory of Open Access Journals (Sweden)

    Pavlović Momčilo

    2007-01-01

    Full Text Available Introduction. Henoch-Schönlein purpura (HSP is the most common vascular disease of childhood. It is a multisystem disease most commonly affecting the skin, joints, gastrointestinal tract, and kidneys, but other organs may be affected, too. Gastrointestinal involvement occurs in approximately 65-90% of patients, ranging from mild symptoms such as abdominal pain, nausea, and vomiting, to more severe manifestations such as gastrointestinal bleeding and intussusception. In most cases, HSP spontaneously resolves without treatment. The use of corticosteroids is controversial and usually reserved for severe systemic manifestations. Some authors suggest that the abdominal pain and gastrointestinal hemorrhage of HSP may respond to steroids, with some suggesting that there is a benefit in their use and describing a regimen. Case outline. This is a case report of HSP in a fourteen year-old boy with abdominal pain and hematemesis. Upper endoscopy showed an edematous and erythematous change in the body of the stomach and purpuric lesions in the duodenum, while multiple erosions were found in the antral area. Parenteral corticosteroid therapy with gastric acid secretion inhibitor administration led to regression of gastrointestinal symptoms on the seventh day, with relapses on the fourth and sixth day. Peroral administration of corticosteroids and gradual decrease of daily doses started on the eighth day of abdominal symptoms. New purpuric skin rashes appeared during six weeks. Conclusion. Corticosteroid therapy with gastric acid secretion inhibitors showed a positive effect in our patient with a severe form of HSP accompanied by abdominal pain and gastrointestinal hemorrhage. .

  13. Sediment budgets of unglaciated alpine catchments - the example of the Johnsbach and Schöttlbach valleys in Styria

    Science.gov (United States)

    Sass, Oliver; Rascher, Eric; Stangl, Johannes; Lutzmann, Silke

    2017-04-01

    Extensive research has been performed in glacier forefields and in glaciated catchments in order to predict their future behaviour in a warming climate. However, the majority of medium-scale torrential catchments in the European Alps are non-glaciated and their response to disturbance events (e.g. changing climate) is more subtle and hard to predict. We report from two torrential catchments in the Eastern Alps, the Johnsbach and the Schöttlbach valleys, that have been monitored for several years. The catchments are located in Styria (Austria) and are remarkably similar in terms of size (60-70 km3) and elevation (600/800 - 2400 m). The main difference is the geological setting of the sediment delivering areas which is limestone and brittle dolomite at Johnsbach, and a prominent late-pleistocene valley fill at Schöttlbach, respectively. Slope processes in both areas were monitored by means of repeated TLS surveys of active slope and channel areas and by ALS and/or UAV surveys. Fluvial transport in the main channels was measured using Helly-Smith samplers and recorded continuously by means of new developed, low-budget sediment impact sensors (SIS). In both areas, the catchment output was quantified: by regular surveys of a retention basin at Schöttlbach and by a bedload measurement station (geophone sill) at Johnsbach. The results show that at Johnsbach, the sediment source areas are active tributary trenches in the lower third of the catchment. The sediments derive from brittle dolomite rockwalls and are transported to the main river episodically during rainstorm events. In a 2-yr period, 7400 m3 yr-1 were eroded in the surveyed areas and 9900 m3 yr-1 m3 yr-1 were deposited; of this amount, only a minor portion of 650 m3 yr-1 reached the Johnsbach River. The degree of coupling between tributaries and creek is strongly influenced by anthropogenic measures, e.g. former disturbance by gravel mining and undersized bridge openings. Besides limited bank erosion

  14. Thiolato-technetium complexes. 5. Synthesis, characterization, and electrochemical properties of bis(o-phenylenebis(dimethylarsine))technetium(II) and -technetium(III) complexes with thiolato ligands. Single-crystal structural analyses of trans-[Tc(SCH3)2(DIARS)2]PF6 and trans-[Tc(SC6H5)2(DIARS)2]0

    International Nuclear Information System (INIS)

    Konno, Takumi; Heineman, W.R.; Deutsch, E.; Kirchhoff, J.R.; Heeg, M.J.; Stuckey, J.A.

    1992-01-01

    Three different thiols have been brought into reaction with trans-[Tc(OH)(O)(DIARS) 2 ] 2+ to produce initially the Tc(II) complex, [Tc(SR) 2 (DIARS) 2 ] 0 , which can be oxidized to the Tc(III) complex, [Tc(SR) 2 (DIARS) 2 ] + (DIARS = o-phenylenebis(dimethylarsine)). In the case of SR = SCH 3 and SCH 2 C 6 H 5 , the Tc(II) and Tc(III) products were found to be in the trans geometry, while for SR = SC 6 H 5 , both cis and trans isomers were generated. Two of the complexes were structurally characterized by X-ray diffraction. trans-[Tc(SCH 3 ) 2 (DIARS) 2 ]PF 6 , chemical formula TcAs 4 S 2 PF 6 C 22 H 38 , crystallizes in the monoclinic space group. The Tc atom occupies an inversion center. Representative elemental analyses, FAB mass spectra, and visible-UV spectra are reported. Electrochemical and spectroelectrochemical measurements were taken on trans-[Tc(SCH 3 ) 2 (DIARS) 2 ] + , trans-[Tc(SCH 2 C 6 H 5 ) 2 (DIARS) 2 ] + , and cis-[Tc(SC 6 H 5 ) 2 (DIARS) 2 ] + , which exhibit a reversible Tc(III/II) redox couple in the range -0.32 to -0.47 V vs. Ag/AgCl. Another redox couple is present in the range -1.22 to -1.70 V; this is ascribed to Tc(II/I) and is reversible only for SR = SCH 2 C 6 H 5 at 20C. At room temperature, chemically irreversible couples are exhibited at ca. +1.0 V for Tc(IV/III)

  15. Disposal of residues according paragraph 97 StrlSchV - Efficient self control and handling of applications for release from regulatory control; Entsorgung von Rueckstaenden nach paragraph 97 StrlSchV - effektive Selbstueberwachung und Bearbeitung von Entlassungsverfahren

    Energy Technology Data Exchange (ETDEWEB)

    Gellermann, R. [HGN Hydrogeologie GmbH, Braunschweig (Germany)

    2005-07-01

    To control residues according to paragraph 97 of the German Radiation Protection Ordinance (StrlSchV), the ordinance earmarks a self - control of involved companies in the case of very low specific activities, an authorisation of release from regulatory control to disposal in the case of higher specific activities and a balancing of disposed activities in the case of large amounts. The realisation of this regulation requires the exchange of information between owners of residues, disposing companies and authorities. In order to make this information available and controllable in an efficient way, a well structured system of documents was developed analogue to an existing system in waste management. Practical experiences with this system are discussed. (orig.)

  16. Engineered nickel oxide nanoparticle causes substantial physicochemical perturbation in plants

    Science.gov (United States)

    Manna, Indrani; Bandyopadhyay, Maumita

    2017-11-01

    Concentration of engineered NiO-NP in nature is on the rise, owing to large scale industrial uses and human interventions, which have accreted the scope of exposure especially at the primary trophic levels of the ecosystem. Nickel content in air, drinking water and soil is already above permissible limits in most parts of the developed world. Though nickel oxide is an essential micronutrient in the animal system, it has already been graded as a human carcinogen by WHO, and numerous studies have established the toxic nature of nickel in higher dosage in the animal system. Though studies depicting toxicity and bioaccumulation of nickel in plants is documented, the interaction of nickel oxide nanoparticle with plants is not fully a well-studied, well elucidated topic. What is known is that, exposure to nickel oxide nanoparticle, arouses stress response and leads to cytotoxicity and growth retardation in a handful of plants, a defined work on the intricate physicochemical cellular responses and genotoxic challenges has been so far absent. We have tried to fill in such gaps with this study. We planned the work around pertinent hypotheses like: whether NiO-NP cause cytotoxicity in a model plant system (Allium cepa L.)?If so, does internalization of nickel ion (the potent toxic) take place in the tissue? Does internalized NiO-NP create furore in the antioxidant enzyme system of the plant leading to cytotoxicity? In that case, whether the ENP causes genotoxicity and leads to pycknosis of the cell. The study has been designed to assess the change in biochemical profile and genotoxicity potential of NiO-NP at a wide range of concentrations using root tips of Allium cepa L., the model system for study of cytotoxicity and genotoxicity, and four of its closest relatives, Allium sativum L., Allium schoenoprasum L., Allium porrum L., Allium fistulosum L., chosen for their immense economic importance. Growing root tips were treated with seven different concentrations of Ni

  17. Estudo da validade e confiabilidade intra e interobservador da versão modificada do teste de Schöber modificado em indivíduos com lombalgia Study of validity and intra and inter-observer reliability of modified-modified Schöber test in subjects with low-back pain

    Directory of Open Access Journals (Sweden)

    Christiane de Souza Guerino Macedo

    2009-09-01

    Full Text Available Em pacientes com lombalgia, mensura-se a amplitude de movimento (ADM da coluna lombar por meio da versão modificada do teste de Schöber modificado (MTSM, mas suas propriedades psicométricas não são comprovadas para uso clínico. Este estudo verificou a validade e confiabilidade intra e interobservador do MTSM em indivíduos com lombalgia, comparando as medidas da ADM com as obtidas por meio de radiografia, método considerado padrão-ouro. Participaram 20 voluntários com lombalgia, de ambos os sexos, funcionários de um Hospital Universitário. O MTSM foi aplicado duas vezes por dois avaliadores. As medidas obtidas pelo teste e por radiografia foram comparadas usando o coeficiente de correlação de Pearson, obtendo-se r=0,14, ou seja, correlação fraca. O coeficiente de correlação intraclasse (CCI dos MTSM intra-observador foi 0,96 (IC 95% 0,91;0,98 e interobservador 0,93 (IC 95% 0,84;0,97, indicando alta confiabilidade; o teste de Bland & Altman mostrou alta concordância intra e interobservador, com valores de -0,21 e -0,28, respectivamente. Embora tenha sido encontrada alta confiabilidade intra e interobservador na aplicação da versão modificada do teste de Schöber modificado, este apresentou baixa validade para medir a ADM da coluna lombar, quando comparado ao padrão-ouro.In patients with low-back pain the lumbar spine range of motion (ROM is often measured by the modified version of the modified Schöber test (MMST, but its psychometric properties have not been ascertained for clinical use. The purpose here was to verify intra and inter-observer validity and reliability of the MMST in subjects with low-back pain, and to compare obtained ROM measures to those obtained by radiography, taken as gold standard. The study involved 20 subjects with chronic low-back pain, of both sexes, employees at a university hospital. The MMST was applied twice by two examiners each. The Pearson correlation coefficient found when comparing

  18. Henoch-Schönlein purpura in children: its relation to oral and to oral and oral and dental health

    Directory of Open Access Journals (Sweden)

    Arlette Suzy Puspa Pertiwi

    2012-09-01

    Full Text Available > Background: Henoch-Schönlein purpura (HSP is a rare systemic small vessel vasculitis, which commonly occur in childrenbetween 2 and 10 years of age. The course of the disease is often self-limiting, although may manifest long-term renal morbidity. Theseverity of renal involvement decides about the prognosis of this disease. Many factors can trigger the disease attack, which is the mostcommon is bacterial invasion. Since the oral cavity is often refer as infectious foci to other part of the body, it seemed rationally tobe part that contribute the course of disease, thus management of these infectious foci, if possible, gives rise to an astoundingly goodprognosis. Purpose: This paper will describe a review on HSP and the possible association with oral and dental health since it mightbe related to the prognosis of HSP. reviews: Rashes in children are common; they may develop a rash after prescription of antibiotics.Nevertheless there are some childhood diseases that may manifest a rash presentation, such as HSP. It is important for pediatric dentistto have knowledge about HSP and consider the possibility of dental treatment or disease as potential triggers. Conclusion: Oral anddental condition may be the trigger cause of HSP attack. Therefore, it is important for pediatric dental practitioner to be aware of thecourse of the disease in order to limit the expanding complications.> latar belakang: Henoch-Schönlein purpura (HSP merupakan vaskulitis pembuluh darah kecil sistemik yang jarang terjadi danbiasanya menyerang anak usia 2 hingga 10 tahun. Penyakit tersebut seringkali dapat sembuh sendiri, tetapi pada jangka panjangdapat bermanifestasi dengan morbiditas ginjal. Keparahan keterlibatan ginjal menentukan prognosis penyakit. Banyak faktor yangdapat memicu serangan penyakit, tersering adalah invasi bakteri. Karena rongga mulut sering kali merupakan fokus infeksi terhadapbagian lain dari tubuh, maka mempunyai peluang sebagai faktor pemicu

  19. [Clinical characteristics of Henoch-Schönlein purpura in children].

    Science.gov (United States)

    Liu, Li-Jun; Yu, Jing; Li, Yu-Ning

    2015-10-01

    To explore the clinical characteristics of Henoch-Schönlein purpura (HSP) in children. The clinical data of 325 hospitalized children who were diagnosed with HSP between June 2012 and June 2014 were analyzed retrospectively. In the 325 children with HSP, the incidence of HSP was higher in winter and spring, with 33.9% and 27.4%, respectively. Infection was the major factor to induce HSP (57.2%). The incidence of renal damage in children with purpura accompanied by abdominal symptoms and children with purpura accompanied by abdominal and joint symptoms was 60.3% and 48.9%, respectively, with statistically significant differences compared with children with purpura alone (Ppurpura nephritis, the pathological grades of IIIa and IIIb were more common, accounting for 28% and 31%, respectively. In 325 children, an increased serum D-dimer level was observed in 260 children (80.0%), an increased peripheral IgA content in 101 children (46.3%), and a decreased CD4+ cell percentage in 62 children (56.4%). A high incidence of HSP is often seen in spring and winter. HSP is often induced by upper respiratory tract infection. Renal damage is more likely to occur in children with digestive tract symptoms, with IIIa and IIIb as the common pathological grades of renal damage.

  20. Combination of behaviorally sub-effective doses of glutamate NMDA and dopamine D1 receptor antagonists impairs executive function.

    Science.gov (United States)

    Desai, Sagar J; Allman, Brian L; Rajakumar, Nagalingam

    2017-04-14

    Impairment of executive function is a core feature of schizophrenia. Preclinical studies indicate that injections of either N-methyl d-aspartate (NMDA) or dopamine D 1 receptor blockers impair executive function. Despite the prevailing notion based on postmortem findings in schizophrenia that cortical areas have marked suppression of glutamate and dopamine, recent in vivo imaging studies suggest that abnormalities of these neurotransmitters in living patients may be quite subtle. Thus, we hypothesized that modest impairments in both glutamate and dopamine function can act synergistically to cause executive dysfunction. In the present study, we investigated the effect of combined administration of "behaviorally sub-effective" doses of NMDA and dopamine D 1 receptor antagonists on executive function. An operant conditioning-based set-shifting task was used to assess behavioral flexibility in rats that were systemically injected with NMDA and dopamine D 1 receptor antagonists individually or in combination prior to task performance. Separate injections of the NMDA receptor antagonist, MK-801, and the dopamine D 1 receptor antagonist, SCH 23390, at low doses did not impair set-shifting; however, the combined administration of these same behaviorally sub-effective doses of the antagonists significantly impaired the performance during set-shifting without affecting learning, retrieval of the memory of the initial rule, latency of responses or the number of omissions. The combined treatment also produced an increased number of perseverative errors. Our results indicate that NMDA and D 1 receptor blockade act synergistically to cause behavioral inflexibility, and as such, subtle abnormalities in glutamatergic and dopaminergic systems may act cooperatively to cause deficits in executive function. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Henoch-Schönlein purpura without systemic involvement beginning with acute scrotum and mimicking torsion of testis

    Directory of Open Access Journals (Sweden)

    Levent Verim

    2013-04-01

    Full Text Available Henoch-Schönlein purpura (HSP is the most common systemic vasculitis in children. Typical presentations of HSP are palpable purpura of the small vessels in the hips and lower limbs, abdominal pain, arthritis, and hematuria. Scrotal involvement manifested by the presence of scrotal pain and swelling during the course of the disease is rarely seen. HSP without systemic involvement with acute scrotum mimicking testicular torsion is even rare in the medical literature. In most cases, patients with this disease achieve complete recovery. Herein, we report an interesting HSP case with skin symptoms but without systemic involvement and then progression to acute scrotum resembling torsion of testis.

  2. Schönheit und andere Provokationen - Eine neue evolutionsbiologische Theorie der Kunst

    Science.gov (United States)

    Junker, Thomas

    Die Evolution hat viele spektakuläre Phänomene hervorgebracht - von der Eleganz des Vogelflugs über die gigantischen Körper der Dinosaurier und die farbenprächtige Vielfalt der Korallenriffe bis hin zu ihrem jüngsten Geniestreich - der menschlichen Kunst. Die schönen Künste - Malerei, Bildhauerei und Architektur, Theater, Tanz, Oper und Filmkunst, Musik und Literatur - Produkte der Evolution? Diese Vorstellung mutet vielen Menschen fremd an, aber wie könnte es anders sein? Denn wenn Charles Darwin recht hat, dann sind nicht nur die körperlichen Merkmale der Menschen als Antworten auf die Erfordernisse des Lebens entstanden, sondern auch ihre geistigen Fähigkeiten und Verhaltensweisen. Im Jahr 1859 hatte er auf den letzten Seiten seines berühmten Buches über die Entstehung der Arten eine kühne Prophezeiung gemacht: Durch die Evolutionstheorie werde es "zu einer bemerkenswerten Revolution in der Naturwissenschaft kommen […]. Die Psychologie wird auf die neue Grundlage gestellt, dass jede geistige Kraft und Fähigkeit notwendigerweise durch graduelle Übergänge erworben wird“ (Darwin 1859, S. 484, 488; Junker 2008).

  3. Schisandrin B protects against solar irradiation-induced oxidative injury in BJ human fibroblasts.

    Science.gov (United States)

    Chiu, Po Yee; Lam, Philip Y; Yan, Chung Wai; Ko, Kam Ming

    2011-06-01

    The effects of schisandrin B (Sch B) and its analogs on solar irradiation-induced oxidative injury were examined in BJ human fibroblasts. Sch B and schisandrin C (Sch C) increased cellular reduced glutathione (GSH) level and protected against solar irradiation-induced oxidative injury. The photoprotection was paralleled by decreases in the elastases-type protease activity and matrix-metalloproteinases-1 expression in solar-irradiated fibroblasts. The cytochrome P-450-mediated metabolism of Sch B or Sch C caused ROS production. The results suggest that by virtue of its pro-oxidant action and the subsequent glutathione antioxidant response, Sch B or Sch C may offer the prospect of preventing skin photo-aging. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Interaktion mit Digitalen Rechtschreibhilfen: Ein Vergleich von Schülertexten. Neue Wege zur Förderung der Rechtschreibkompetenz in der Sekundarstufe I.

    OpenAIRE

    Berndt, Elin-Birgit

    2002-01-01

    Die explorative Studie zeigt beispielhaft die Reichweite der Interaktion mit digitalen Rechtschreibhilfen in der Sekundarstufe I auf. Die im Schreibprozeß am Computer verfügbaren digitalen Rechtschreibhilfen - ABC-Prüfung der Textverarbeitungssoftware, digitale Rechtschreibwörterbücher und Thesaurus - erweisen sich für Schüler, die Schwierigkeiten mit der Orthographie haben, als sehr nützlich. Es gelingt ihnen nach der Überarbeitung ihrer Texte am PC orthographisch erheblich fehlerfreiere Tex...

  5. O conceito sócio-filosófico de Alfredo Schütz e suas implicações epistemológicas para o campo da Comunicação

    Directory of Open Access Journals (Sweden)

    Ulrike Schröder

    2006-12-01

    Full Text Available No seu conceito de uma sociologia interpretativa, o sociólogo Alfred Schütz procura realizar uma análise profunda do nosso "mundo da vida" (s, partindo da convicção de que este mundo de sentido não representa uma realidade objetiva, mas sim, uma realidade interpretada e válida intersubjetivamente. Por isso, também não vivemos simplesmente em um uni-verso fixo, mas sim, em multi-versos, cada um marcado por um outro estilo epistemológico. O artigo apresenta as características essenciais da teoria de Schütz, focalizando a atualidade do seu conceito, que indica possibilidades de tornar este fundamento teórico base para estudos empíricos no campo da comunicação hoje em dia.

  6. Mise en pratique du schéma 2BSvs dans le groupe industriel Sofiprotéol : étude de cas sur toute la filière (de l’agriculteur au pétrolier

    Directory of Open Access Journals (Sweden)

    Guizouarn Kristell

    2015-01-01

    Full Text Available Pour réduire sensiblement les émissions de CO liées aux transports routiers, l’Union européenne mise sur le développement des biocarburants, en respectant des conditions de durabilité. Afin de répondre à cette obligation et d’être en mesure de démontrer la conformité du biodiesel à ces critères, depuis l’agriculteur jusqu’au distributeur pétrolier, la filière des oléagineux a engagé la rédaction d’un schéma de vérification volontaire : 2BSvs, pour Biomasse Biocarburant Schéma volontaire sur la durabilité. Reconnu par la Commission Européenne le 19 juillet 2011, le schéma 2BSvs couvre l’ensemble de la chaîne de production des biocarburants, du producteur de biomasse à l’entrée dans un entrepôt sous douanes. À travers une étude de cas sur toute la filière, de l’agriculteur au pétrolier, cet article présente les implications pour les acteurs de la filière oléagineuse, les changements intervenus depuis avril 2013, et les défis futurs à relever.

  7. Establishing Substantial Equivalence: Transcriptomics

    Science.gov (United States)

    Baudo, María Marcela; Powers, Stephen J.; Mitchell, Rowan A. C.; Shewry, Peter R.

    Regulatory authorities in Western Europe require transgenic crops to be substantially equivalent to conventionally bred forms if they are to be approved for commercial production. One way to establish substantial equivalence is to compare the transcript profiles of developing grain and other tissues of transgenic and conventionally bred lines, in order to identify any unintended effects of the transformation process. We present detailed protocols for transcriptomic comparisons of developing wheat grain and leaf material, and illustrate their use by reference to our own studies of lines transformed to express additional gluten protein genes controlled by their own endosperm-specific promoters. The results show that the transgenes present in these lines (which included those encoding marker genes) did not have any significant unpredicted effects on the expression of endogenous genes and that the transgenic plants were therefore substantially equivalent to the corresponding parental lines.

  8. Substantial Union or Substantial Distinction of Mind and Body in Descartes' Metaphysics

    Directory of Open Access Journals (Sweden)

    Fahime Jamei

    2009-01-01

    Full Text Available According to Descartes’ metaphysics there are two different kinds of substances in the world of creatures: “thinking substance” and “extended substance” or soul and matter. In Descartes’ philosophy the soul is equal to the mind and considered as a “thinking substance”. This immaterial substance is the essence of the human being. Body, being considered as a “matter“, is an “extended substance” and entirely distinct from the soul. The soul, therefore, exists and may be known prior to body and, not being corporeal, can exist after human death. Hence, Descartes can prove the immortality of human soul in the framework of the principle of substantial distinction. On the other hand, as a physiologist and psychologist, Descartes indeed believes in mind-body union, so that some causal interactions between mind and body show their substantial union. In this essay, the authors show that Descartes faces a serious problem in combining substantial union of mind and body with their substantial distinction; despite of his efforts in introducing the idea of pineal gland, the problem remains unsolved. Therefore it seems that as he cannot dispense with his only reason for proving the immortality of human soul, he has to hold the mind-body distinction theory in his metaphysics. Indeed, Descartes prefers to support the distinction theory rather than union theory in confronting a thesis and an antithesis stating one of two theories

  9. Substantial :union: or Substantial Distinction of Mind and Body in Descartes\\' Metaphysics

    Directory of Open Access Journals (Sweden)

    f Jamei

    2009-06-01

    Full Text Available According to Descartes’ metaphysics there are two different kinds of substances in the world of creatures: “thinking substance” and “extended substance” or soul and matter. In Descartes’ philosophy the soul is equal to the mind and considered as a “thinking substance”. This immaterial substance is the essence of the human being. Body, being considered as a “matter“, is an “extended substance” and entirely distinct from the soul. The soul, therefore, exists and may be known prior to body and, not being corporeal, can exist after human death. Hence, Descartes can prove the immortality of human soul in the framework of the principle of substantial distinction. On the other hand, as a physiologist and psychologist, Descartes indeed believes in mind-body :union:, so that some causal interactions between mind and body show their substantial :union:. In this essay, the authors show that Descartes faces a serious problem in combining substantial :union: of mind and body with their substantial distinction despite of his efforts in introducing the idea of pineal gland, the problem remains unsolved. Therefore it seems that as he cannot dispense with his only reason for proving the immortality of human soul, he has to hold the mind-body distinction theory in his metaphysics. Indeed, Descartes prefers to support the distinction theory rather than :union: theory in confronting a thesis and an antithesis stating one of two theories.

  10. Les schémas de sélection ovins laitiers en France : utilisation et importance des techniques modernes de reproduction

    OpenAIRE

    Astruc, J.M.; Lagriffoul, G.; Belloc, J.P.; Briois, M.; Cachenaut, J.B.; Horent, M.H.; Teinturier, M.H.

    1995-01-01

    La mise en oeuvre de programmes de sélection laitière, à l’échelle de toute une population ovine, suppose de développer un travail de sélection entre éleveurs, fondé sur l’organisation et la valorisation de liens génétiques entre troupeaux, essentiellement grâce à l’utilisation de l’IA. La situation en France est à cet égard révélatrice des différents niveaux d’organisation des schémas de sélection.

  11. 24 CFR 902.79 - Substantial default.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Substantial default. 902.79 Section... PUBLIC HOUSING ASSESSMENT SYSTEM PHAS Incentives and Remedies § 902.79 Substantial default. (a) Events or conditions that constitute substantial default. The following events or conditions shall constitute...

  12. Third statutory ordinance for assignment of competence for environmental radioactivity measuring and evaluation under the German Preventive Radiation Protection Act (StrSchVG). As of 16 October 1997

    International Nuclear Information System (INIS)

    1997-01-01

    The German Bundesamt fuer Strahlenschutz (Radiation Protection Office) is assigned the competence to perform the necessary activities for measurement and large-area monitoring of ambient gamma dose rates on behalf of the Federal Government in compliance with the German Preventive Radiation Protection Act (StrSchVG). (orig./CB) [de

  13. Longitudinal study of microvascular involvement by nailfold capillaroscopy in children with Henoch-Schönlein purpura.

    Science.gov (United States)

    Zampetti, Anna; Rigante, Donato; Bersani, Giulia; Rendeli, Claudia; Feliciani, Claudio; Stabile, Achille

    2009-09-01

    The aim of this study is to describe by video-nailfold capillaroscopy the microvascular involvement and capillary changes in children with Henoch-Schönlein purpura (HSp) and to establish a possible correlation with clinical outcome. Thirty-one patients underwent capillaroscopic evaluation through a videomicroscope during the acute phase and after 6 months. Twenty sex/age-matched controls were also examined. All capillaroscopic variables were statistically examined in combination with laboratoristic/clinical data. Architectural and morphological changes recorded during the acute phase were statistically significant in comparison to the controls (p capillaroscopy changes, laboratoristic/clinical data, and outcome. Video-nailfold capillaroscopy can be a simple tool to evaluate microvascular abnormalities in the acute phase of HSp, and the persistence of oedema could suggest an incomplete disease resolution at a microvascular level.

  14. The role of multiple dopamine receptors in apomorphine and N-n-propylnorapomorphine-induced climbing and hypothermia.

    Science.gov (United States)

    Moore, N A; Axton, M S

    1990-03-20

    Apomorphine and N-n-propylnorapomorphine (NPA) were compared for their ability to induce stereotyped cage climbing and hypothermia in mice. Climbing behavior was produced by similar doses of apomorphine and NPA (0.625-2.5 mg/kg s.c.), whereas NPA was 43 times more potent than apomorphine in inducing a hypothermic response. SKF38393 caused a shift to the left in the dose-response curve for NPA-induced climbing, the ED50 changing from 0.98 to 0.014 mg/kg. SKF38393 had no effect on apomorphine-induced climbing behaviour. The climbing response produced by apomorphine was antagonised by both D-1 and D-2 antagonists. Climbing behaviour induced by NPA (2.5 mg/kg) could be antagonised by SCH23390 but not by clebopride, however climbing behaviour induced by a low dose of NPA (0.06 mg/kg) plus SKF38393 could be blocked by both D-1 and D-2 receptor antagonists. The hypothermic responses produced by either apomorphine or NPA could only be reversed by the selective D-2 antagonist, clebopride. These results demonstrate that dopamine agonist-induced stereotyped cage climbing requires both D-1 and D-2 receptor stimulation, whereas the hypothermic response is D-2-mediated. The results also show that it is possible to assess the relative activity of a dopamine agonist at D-1 or D-2 receptors in vivo by comparing the ability of the compound to induce hypothermia and climbing behaviour.

  15. Influence of the dopaminergic system, CREB, and transcription factor-κB on cocaine neurotoxicity

    International Nuclear Information System (INIS)

    Planeta, C.S.; Lepsch, L.B.; Alves, R.; Scavone, C.

    2013-01-01

    Cocaine is a widely used drug and its abuse is associated with physical, psychiatric and social problems. Abnormalities in newborns have been demonstrated to be due to the toxic effects of cocaine during fetal development. The mechanism by which cocaine causes neurological damage is complex and involves interactions of the drug with several neurotransmitter systems, such as the increase of extracellular levels of dopamine and free radicals, and modulation of transcription factors. The aim of this review was to evaluate the importance of the dopaminergic system and the participation of inflammatory signaling in cocaine neurotoxicity. Our study showed that cocaine activates the transcription factors NF-κB and CREB, which regulate genes involved in cellular death. GBR 12909 (an inhibitor of dopamine reuptake), lidocaine (a local anesthetic), and dopamine did not activate NF-κB in the same way as cocaine. However, the attenuation of NF-κB activity after the pretreatment of the cells with SCH 23390, a D1 receptor antagonist, suggests that the activation of NF-κB by cocaine is, at least partially, due to activation of D1 receptors. NF-κB seems to have a protective role in these cells because its inhibition increased cellular death caused by cocaine. The increase in BDNF (brain-derived neurotrophic factor) mRNA can also be related to the protective role of both CREB and NF-κB transcription factors. An understanding of the mechanisms by which cocaine induces cell death in the brain will contribute to the development of new therapies for drug abusers, which can help to slow down the progress of degenerative processes

  16. Influence of the dopaminergic system, CREB, and transcription factor-κB on cocaine neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Planeta, C.S. [Laboratório de Neuropsicofarmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Lepsch, L.B.; Alves, R.; Scavone, C. [Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil)

    2013-10-15

    Cocaine is a widely used drug and its abuse is associated with physical, psychiatric and social problems. Abnormalities in newborns have been demonstrated to be due to the toxic effects of cocaine during fetal development. The mechanism by which cocaine causes neurological damage is complex and involves interactions of the drug with several neurotransmitter systems, such as the increase of extracellular levels of dopamine and free radicals, and modulation of transcription factors. The aim of this review was to evaluate the importance of the dopaminergic system and the participation of inflammatory signaling in cocaine neurotoxicity. Our study showed that cocaine activates the transcription factors NF-κB and CREB, which regulate genes involved in cellular death. GBR 12909 (an inhibitor of dopamine reuptake), lidocaine (a local anesthetic), and dopamine did not activate NF-κB in the same way as cocaine. However, the attenuation of NF-κB activity after the pretreatment of the cells with SCH 23390, a D1 receptor antagonist, suggests that the activation of NF-κB by cocaine is, at least partially, due to activation of D1 receptors. NF-κB seems to have a protective role in these cells because its inhibition increased cellular death caused by cocaine. The increase in BDNF (brain-derived neurotrophic factor) mRNA can also be related to the protective role of both CREB and NF-κB transcription factors. An understanding of the mechanisms by which cocaine induces cell death in the brain will contribute to the development of new therapies for drug abusers, which can help to slow down the progress of degenerative processes.

  17. SUBSTANTIAL EXCEPTIONS AND (DELIMITATIONS OF THE POWERS OF THE JUDGES ON CIVIL PROCEDURAL LAW

    Directory of Open Access Journals (Sweden)

    Igor Raatz

    2017-08-01

    Full Text Available This essay aims to unveil the role of the substantial exceptions on delimiting the powers of the judges on civil procedural law, especially regarding the ex officio judicial activity. This way, under a phenomenological method and based on a vision of guarantee of rights on procedural law, the article offers a brief explanation of the question concerning the content of the object under litigation and its role of (delimiting the powers of the judges. The work hypothesis is the addition of the substantial exceptions among the content of the object under litigation, along with the claim itself and the cause of action. The results lie on the premise that, by the substantial exceptions, the defendant extends the object under litigation – which is formed dynamically on civil procedure. The conclusion points towards the idea that the substantial exceptions act in a way of limiting the ex officio judicial activity on civil procedural law

  18. pH homeostasis links the nutrient sensing PKA/TORC1/Sch9 ménage-à-trois to stress tolerance and longevity.

    Science.gov (United States)

    Deprez, Marie-Anne; Eskes, Elja; Wilms, Tobias; Ludovico, Paula; Winderickx, Joris

    2018-01-12

    The plasma membrane H + -ATPase Pma1 and the vacuolar V-ATPase act in close harmony to tightly control pH homeostasis, which is essential for a vast number of physiological processes. As these main two regulators of pH are responsive to the nutritional status of the cell, it seems evident that pH homeostasis acts in conjunction with nutrient-induced signalling pathways. Indeed, both PKA and the TORC1-Sch9 axis influence the proton pumping activity of the V-ATPase and possibly also of Pma1. In addition, it recently became clear that the proton acts as a second messenger to signal glucose availability via the V-ATPase to PKA and TORC1-Sch9. Given the prominent role of nutrient signalling in longevity, it is not surprising that pH homeostasis has been linked to ageing and longevity as well. A first indication is provided by acetic acid, whose uptake by the cell induces toxicity and affects longevity. Secondly, vacuolar acidity has been linked to autophagic processes, including mitophagy. In agreement with this, a decline in vacuolar acidity was shown to induce mitochondrial dysfunction and shorten lifespan. In addition, the asymmetric inheritance of Pma1 has been associated with replicative ageing and this again links to repercussions on vacuolar pH. Taken together, accumulating evidence indicates that pH homeostasis plays a prominent role in the determination of ageing and longevity, thereby providing new perspectives and avenues to explore the underlying molecular mechanisms.

  19. Henoch-Schönlein Purpura in Northern Spain

    Science.gov (United States)

    Calvo-Río, Vanesa; Loricera, Javier; Mata, Cristina; Martín, Luis; Ortiz-Sanjuán, Francisco; Alvarez, Lino; González-Vela, M. Carmen; González-Lamuño, Domingo; Rueda-Gotor, Javier; Fernández-Llaca, Héctor; González-López, Marcos A.; Armesto, Susana; Peiró, Enriqueta; Arias, Manuel; González-Gay, Miguel A.; Blanco, Ricardo

    2014-01-01

    Abstract The severity of clinical features and the outcomes in previous series of patients reported with Henoch-Schönlein purpura (HSP) vary greatly, probably due to selection bias. To establish the actual clinical spectrum of HSP in all age groups using an unselected and wide series of patients diagnosed at a single center, we performed a retrospective review of 417 patients classified as having HSP according to the criteria proposed by Michel et al. Of 417 patients, 240 were male and 177 female, with a median age at the time of disease diagnosis of 7.5 years (interquartile range [IQR], 5.3–20.1 yr). Three-quarters of the patients were children or young people aged 20 years or younger (n = 315), and one-quarter were adults (n = 102). The most frequent precipitating events were a previous infection (38%), usually an upper respiratory tract infection, and/or drug intake (18.5%) shortly before the onset of the vasculitis. At disease onset the most common manifestations were skin lesions (55.9%), nephropathy (24%), gastrointestinal involvement (13.7%), joint symptoms (9.1%), and fever (6.2%). Cutaneous involvement occurring in all patients, mainly purpuric skin lesion, was the most common manifestation when the vasculitis was fully established, followed by gastrointestinal (64.5%), joint (63.1%), and renal involvement (41.2%). The main laboratory findings were leukocytosis (36.7%), anemia (8.9%), and increased serum IgA levels (31.7%). The most frequent therapies used were corticosteroids (35%), nonsteroidal antiinflammatory drugs (14%), and cytotoxic agents (5%). After a median follow-up of 12 months (IQR, 2–38 mo), complete recovery was observed in most cases (n = 346; 83.2%), while persistent, usually mild, nephropathy was observed in only 32 (7.7%) cases. Relapses were observed in almost a third of patients (n = 133; 31.9%). In conclusion, although HSP is a typical vasculitis affecting children and young people, it is not uncommon in adults. The prognosis is

  20. Pitfalls in hemostasis exploration, a case report of a girl with Henoch-Schönlein type vasculitis

    Directory of Open Access Journals (Sweden)

    Arghirescu Smaranda

    2017-07-01

    Full Text Available The adequate performance and correct interpretation of assays for coagulation factor inhibitors play a critical role for the hemostasis laboratory. Both, false positive and false negative inhibitor assays may be reported, leading to erroneous patient’s management. Therefore, we decided to present a case with a spurious image of an exceptionally rare acquired combined haemophilia A, B and C, with severe factor ( F VIII, IX and XI deficiency, associated with high titre anti - F VIII, IX and XI inhibitors in a 4 years old girl with Henoch-Schönlein type vasculitis. Finally, performing, beside coagulometric methods also antigenic ELISA assays, we had to invalidate the diagnosis. The performance of antiphospholipd antibodies clarified the diagnosis , finally concluding as definite diagnosis Transient Lupus Anticoagulant Syndrome, with decisive impact on therapy and follow-up.

  1. Test-retest measurements of dopamine D{sub 1}-type receptors using simultaneous PET/MRI imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kaller, Simon; Patt, Marianne; Becker, Georg-Alexander; Luthardt, Julia; Meyer, Philipp M.; Werner, Peter; Barthel, Henryk; Bresch, Anke; Sabri, Osama [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Rullmann, Michael [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig (Germany); Girbardt, Johanna [Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig (Germany); Fritz, Thomas H. [Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig (Germany); University of Gent, Institute for Psychoacoustics and Electronic Music (IPEM), Ghent (Belgium); Hesse, Swen [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Leipzig University Medical Centre, Integrated Research and Treatment Centre (IFB) Adiposity Diseases, Leipzig (Germany)

    2017-06-15

    The role of dopamine D{sub 1}-type receptor (D{sub 1}R)-expressing neurons in the regulation of motivated behavior and reward prediction has not yet been fully established. As a prerequisite for future research assessing D{sub 1}-mediated neuronal network regulation using simultaneous PET/MRI and D{sub 1}R-selective [{sup 11}C]SCH23390, this study investigated the stability of central D{sub 1}R measurements between two independent PET/MRI sessions under baseline conditions. Thirteen healthy volunteers (7 female, age 33 ± 13 yrs) underwent 90-min emission scans, each after 90-s bolus injection of 486 ± 16 MBq [{sup 11}C]SCH23390, on two separate days within 2-4 weeks using a PET/MRI system. Parametric images of D{sub 1}R distribution volume ratio (DVR) and binding potential (BP{sub ND}) were generated by a multi-linear reference tissue model with two parameters and the cerebellar cortex as receptor-free reference region. Volume-of-interest (VOI) analysis was performed with manual VOIs drawn on consecutive transverse MRI slices for brain regions with high and low D{sub 1}R density. The DVR varied from 2.5 ± 0.3 to 2.9 ± 0.5 in regions with high D{sub 1}R density (e.g. the head of the caudate) and from 1.2 ± 0.1 to 1.6 ± 0.2 in regions with low D{sub 1}R density (e.g. the prefrontal cortex). The absolute variability of the DVR ranged from 2.4% ± 1.3% to 5.1% ± 5.3%, while Bland-Altman analyses revealed very low differences in mean DVR (e.g. 0.013 ± 0.17 for the nucleus accumbens). Intraclass correlation (one-way, random) indicated very high agreement (0.93 in average) for both DVR and BP{sub ND} values. Accordingly, the absolute variability of BP{sub ND} ranged from 7.0% ± 4.7% to 12.5% ± 10.6%; however, there were regions with very low D{sub 1}R content, such as the occipital cortex, with higher mean variability. The test-retest reliability of D{sub 1}R measurements in this study was very high. This was the case not only for D{sub 1}R-rich brain areas, but

  2. Test-retest measurements of dopamine D_1-type receptors using simultaneous PET/MRI imaging

    International Nuclear Information System (INIS)

    Kaller, Simon; Patt, Marianne; Becker, Georg-Alexander; Luthardt, Julia; Meyer, Philipp M.; Werner, Peter; Barthel, Henryk; Bresch, Anke; Sabri, Osama; Rullmann, Michael; Girbardt, Johanna; Fritz, Thomas H.; Hesse, Swen

    2017-01-01

    The role of dopamine D_1-type receptor (D_1R)-expressing neurons in the regulation of motivated behavior and reward prediction has not yet been fully established. As a prerequisite for future research assessing D_1-mediated neuronal network regulation using simultaneous PET/MRI and D_1R-selective ["1"1C]SCH23390, this study investigated the stability of central D_1R measurements between two independent PET/MRI sessions under baseline conditions. Thirteen healthy volunteers (7 female, age 33 ± 13 yrs) underwent 90-min emission scans, each after 90-s bolus injection of 486 ± 16 MBq ["1"1C]SCH23390, on two separate days within 2-4 weeks using a PET/MRI system. Parametric images of D_1R distribution volume ratio (DVR) and binding potential (BP_N_D) were generated by a multi-linear reference tissue model with two parameters and the cerebellar cortex as receptor-free reference region. Volume-of-interest (VOI) analysis was performed with manual VOIs drawn on consecutive transverse MRI slices for brain regions with high and low D_1R density. The DVR varied from 2.5 ± 0.3 to 2.9 ± 0.5 in regions with high D_1R density (e.g. the head of the caudate) and from 1.2 ± 0.1 to 1.6 ± 0.2 in regions with low D_1R density (e.g. the prefrontal cortex). The absolute variability of the DVR ranged from 2.4% ± 1.3% to 5.1% ± 5.3%, while Bland-Altman analyses revealed very low differences in mean DVR (e.g. 0.013 ± 0.17 for the nucleus accumbens). Intraclass correlation (one-way, random) indicated very high agreement (0.93 in average) for both DVR and BP_N_D values. Accordingly, the absolute variability of BP_N_D ranged from 7.0% ± 4.7% to 12.5% ± 10.6%; however, there were regions with very low D_1R content, such as the occipital cortex, with higher mean variability. The test-retest reliability of D_1R measurements in this study was very high. This was the case not only for D_1R-rich brain areas, but also for regions with low D_1R density. These results will provide a solid base

  3. Investigation of H2S separation from H2S/CH4 mixtures using functionalized and non-functionalized vertically aligned carbon nanotube membranes

    Science.gov (United States)

    Gilani, Neda; Towfighi, Jafar; Rashidi, Alimorad; Mohammadi, Toraj; Omidkhah, Mohammad Reza; Sadeghian, Ahmad

    2013-04-01

    Separation of H2S from binary mixtures of H2S/CH4 using vertically aligned carbon nanotube membranes fabricated in anodic aluminum oxide (AAO) template was studied experimentally. Carbon nanotubes (CNTs) were grown in five AAO templates with different pore diameters using chemical vapor deposition, and CNT/AAO membranes with tubular carbon nanotube structure and open caps were selected for separation of H2S. For this, two tubular CNT/AAO membranes were fabricated with the CNT inner diameters of 23 and 8 nm. It was found that permeability and selectivity of the membrane with inner diameter of 23 nm for CNT were independent of upstream feed pressure and H2S feed concentration unlike that of CNT having an inner diameter of 8 nm. Selectivity of these membranes for separation of H2S was obtained in the ranges of 1.36-1.58 and 2.11-2.86, for CNTs with internal diameters of 23 and 8 nm, respectively. In order to enhance the separation of H2S from H2S/CH4 mixtures, dodecylamine was used to functionalize the CNT/AAO membrane with higher selectivity. The results showed that for amido-functionalized membrane, both upstream feed pressure and H2S partial pressure in the feed significantly increased H2S permeability, and selectivity for H2S being in the range of 3.0-5.57 respectively.

  4. Adenosine A2A receptors modulate the dopamine D2 receptor-mediated inhibition of synaptic transmission in the mouse prefrontal cortex.

    Science.gov (United States)

    Real, Joana I; Simões, Ana Patrícia; Cunha, Rodrigo A; Ferreira, Samira G; Rial, Daniel

    2018-05-01

    Prefrontal cortex (PFC) circuits are modulated by dopamine acting on D 1 - and D 2 -like receptors, which are pharmacologically exploited to manage neuropsychiatric conditions. Adenosine A 2A receptors (A 2 A R) also control PFC-related responses and A 2 A R antagonists are potential anti-psychotic drugs. As tight antagonistic A 2 A R-D 2 R and synergistic A 2 A R-D 1 R interactions occur in other brain regions, we now investigated the crosstalk between A 2 A R and D 1 /D 2 R controlling synaptic transmission between layers II/III and V in mouse PFC coronal slices. Dopamine decreased synaptic transmission, a presynaptic effect based on the parallel increase in paired-pulse responses. Dopamine inhibition was prevented by the D 2 R-like antagonist sulpiride but not by the D 1 R antagonist SCH23390 and was mimicked by the D 2 R agonist sumanirole, but not by the agonists of either D 4 R (A-412997) or D 3 R (PD128907). Dopamine inhibition was prevented by the A 2 A R antagonist, SCH58261, and attenuated in A 2 A R knockout mice. Accordingly, triple-labelling immunocytochemistry experiments revealed the co-localization of A 2 A R and D 2 R immunoreactivity in glutamatergic (vGluT1-positive) nerve terminals of the PFC. This reported positive A 2 A R-D 2 R interaction controlling PFC synaptic transmission provides a mechanistic justification for the anti-psychotic potential of A 2 A R antagonists. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  5. „...folglich ich keines Weges einem meiner Mit-Collegen nachtheilig bin...“ Die Deregulierung des habsburgischen Buchhandels unter Joseph II. am Beispiel des Prager Buchdruckers J. N. F. von Schönfeld

    Czech Academy of Sciences Publication Activity Database

    Wögerbauer, Michael

    2009-01-01

    Roč. 34, č. 2 (2009), s. 46-72 ISSN 0340-4528 R&D Projects: GA ČR GA408/08/1545 Institutional research plan: CEZ:AV0Z90560517 Keywords : book studies * Schönfeld, Johann Ferdinand Nepomuk Subject RIV: AJ - Letters, Mass-media, Audiovision

  6. 20 CFR 404.1675 - Finding of substantial failure.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Finding of substantial failure. 404.1675... DISABILITY INSURANCE (1950- ) Determinations of Disability Substantial Failure § 404.1675 Finding of substantial failure. A finding of substantial failure with respect to a State may not be made unless and until...

  7. pH homeostasis links the nutrient sensing PKA/TORC1/Sch9 ménage-à-trois to stress tolerance and longevity

    Directory of Open Access Journals (Sweden)

    Marie-Anne Deprez

    2018-01-01

    Full Text Available The plasma membrane H+-ATPase Pma1 and the vacuolar V-ATPase act in close harmony to tightly control pH homeostasis, which is essential for a vast number of physiological processes. As these main two regulators of pH are responsive to the nutritional status of the cell, it seems evident that pH homeostasis acts in conjunction with nutrient-induced signalling pathways. Indeed, both PKA and the TORC1-Sch9 axis influence the proton pumping activity of the V-ATPase and possibly also of Pma1. In addition, it recently became clear that the proton acts as a second messenger to signal glucose availability via the V-ATPase to PKA and TORC1-Sch9. Given the prominent role of nutrient signalling in longevity, it is not surprising that pH homeostasis has been linked to ageing and longevity as well. A first indication is provided by acetic acid, whose uptake by the cell induces toxicity and affects longevity. Secondly, vacuolar acidity has been linked to autophagic processes, including mitophagy. In agreement with this, a decline in vacuolar acidity was shown to induce mitochondrial dysfunction and shorten lifespan. In addition, the asymmetric inheritance of Pma1 has been associated with replicative ageing and this again links to repercussions on vacuolar pH. Taken together, accumulating evidence indicates that pH homeostasis plays a prominent role in the determination of ageing and longevity, thereby providing new perspectives and avenues to explore the underlying molecular mechanisms.

  8. 20 CFR 416.1075 - Finding of substantial failure.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Finding of substantial failure. 416.1075... AGED, BLIND, AND DISABLED Determinations of Disability Substantial Failure § 416.1075 Finding of substantial failure. A finding of substantial failure with respect to a State may not be made unless and until...

  9. Bone taphonomy of the Schöningen "Spear Horizon South" and its implications for site formation and hominin meat provisioning.

    Science.gov (United States)

    Starkovich, Britt M; Conard, Nicholas J

    2015-12-01

    This paper presents the faunal remains from the new excavation area at the Lower Paleolithic site of Schöningen. The focus of the study is on the southern extension of the main find horizon (Spear Horizon South), which includes the layer that yielded the famous Schöningen spears (13 II-4). Taxonomic data corroborate previous studies, that hominins primarily hunted Equus mosbachensis, a large Pleistocene horse. Equid body part representation at the site suggests that the animals were hunted and butchered locally. There is no evidence for density-mediated attrition in the assemblage. Weathering damage is uncommon, though there is ample evidence that carnivores had access to the bone. Carnivore bite sizes were measured and compared to experimental data provided by previous authors. Based on relationships between bite size and carnivore behavior and body size, we conclude that the primary modifying agents were large carnivores (i.e., wolves or saber-toothed cats). Previous studies show that carnivores often had secondary access to the remains, after hominins. Cut marks are commonly arranged haphazardly on the bones. This may indicate that multiple hominins participated in the butchery of horse skeletons, or that they were butchered over the course of hours or days. Cut marks on axial elements are more "orderly," which probably reflects the physical logistics of orienting one's body in relation to a large carcass. These data differ from sites formed by Middle and Upper Paleolithic hominins, which might suggest that in later times, a system of organized meat provisioning was already in place. Taken together, the faunal evidence from the Spear Horizon South indicates that late Lower Paleolithic hominins using the site understood the behaviors of different prey species, hunted socially to take down large game, and successfully competed with large carnivores on the landscape for primary access to ungulate remains. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Effect of dopamine D1 receptor antagonist SCH23390 and D1 agonist A77636 on active allothetic place avoidance, a spatial cognition task

    Czech Academy of Sciences Publication Activity Database

    Stuchlík, Aleš; Valeš, Karel

    2006-01-01

    Roč. 172, č. 2 (2006), s. 250-255 ISSN 0166-4328 R&D Projects: GA ČR(CZ) GA309/06/1231; GA ČR(CZ) GP309/03/P126; GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : spatial memory * cognition * dopamine Subject RIV: FH - Neurology Impact factor: 2.591, year: 2006

  11. Reflexión sobre la revisoría fiscal desde la sociología fenomenológica de Alfred Schütz

    OpenAIRE

    Cuenú Cabezas, Jairo Emiro

    2014-01-01

    El presente artículo pretende realizar una reflexión sobre la revisoría fiscal, tomando como referencia la teoría socio-fenomenológica del austríaco Alfred Schütz; la cual analiza, entre otras categorías, las relaciones de alteridad en el mundo de la vida cotidiana; mundo que caracteriza como la realidad primaria o fundamental, porque en ésta se da la comunicación, la acción y la intersubjetividad. La intersubjetividad es abordada a partir de la matriz espacio-tiempo, la cual determina que cu...

  12. Radiation protection technology. Specific course for authorized radiation protection representatives according the qualification guidelines technology for the radiation protection regulations (StrlSchV) and X-ray regulation (RoeV). 2. rev. ed.

    International Nuclear Information System (INIS)

    Rahn, Hans-Joachim

    2012-01-01

    The specific course for authorized radiation protection representatives according the qualification guidelines technology for the radiation protection regulations (StrlSchV) and X-ray regulation (RoeV). Covers the following issues: radiation protection - generally; licenses and notifications; scientific fundamentals; dosimetry, surveillance, control, documentation; technical radiation protection; radiation protection calculations.

  13. Joint Affection in Henoch-Schönlein Purpura

    Directory of Open Access Journals (Sweden)

    O.V. Syniachenko

    2016-10-01

    Full Text Available Background. Hemorrhagic vasculitis, or Henoch-Schönlein purpura (HSP, in children has its onset in the form of the articular syndrome in the vast number of patients, which is a part of the diagnostic criteria of this disease. The nature of the arthritis after the disease transformation from the juvenile HSP remains unexplored. In adulthood, articular patho­logy can manifest as migratory intermittent or chronic arthritis, but this information should be clarified. The objective was to study the clinical, X-ray and sonographic features of arti­cular syndrome course in patients with HSP and to evaluate the features of arthropathy in the presence of the disease that began in childhood and adulthood. Materials and methods. The study included 174 patients with HSP (83 % of men and 47 % of women. Childhood-onset vasculitis (on average in 12 years was diagnosed in 92 patients, and adulthood-onset (on avera­ge in 25 years — in 82; I, II and III degree of activity of the pathological process are established at a ratio of 1 : 2 : 2. Results. The joint affection is observed in every second patient with HPS, which is closely related to the patient’s age at the onset of the disease, duration and degree of the activity of pathological process, seropositivity by the high content of immunoglobulin A and rheumatoid factor. At that, clinical, radiological and sonographic nature of the articular syndrome’s course (involving the wrist, hip and sacroiliac joints, the development of aseptic osteonecrosis, bone erosion, meniscitis and intraarti­cular cartilage flaps depend on extraarticular manifestations of the di­sease (lesion of heart, kidney, pancreas, central nervous system. They are accompanied by an increased concentration in the blood of β2-microglobulin and circulating immune complexes that together with the values of fibrinogenemia have predictive value. Dimorphism of HSP, transformed from a juvenile one, is characterized by the less serum levels

  14. Endothelial Functioning and Hemodynamic Parameters in Rats with Subclinical Hypothyroid and the Effects of Thyroxine Replacement.

    Directory of Open Access Journals (Sweden)

    Cuixia Gao

    Full Text Available Subclinical hypothyroidism (SCH and its associations with atherosclerosis (AS and cardiovascular disease remain controversial. The purpose of our study was to observe changes in endothelial functioning and hemodynamics in rats with SCH and to determine whether L-thyroxine (L-T4 administration affects these changes.In total, sixty male Wistar rats were randomly divided into the following three groups with 20 rats each: control euthyroid rats, SCH rats and SCH rats that had been treated with thyroxine (SCH+T4. The SCH rats were induced by administration of 10 mg x kg(-1 x d(-1 methimazole (MMI once daily by gavage for 3 months. The SCH+T4 rats were administered the same dose of MMI for three months in addition to 2 μg x kg(-1 x d(-1 L-T4 once daily by gavage after 45 days of MMI administration. The control rats received physiological saline via gavage.The SCH group had significantly higher thyroid-stimulating hormone (TSH, total cholesterol (TC, low-density lipoprotein cholesterol (LDL-C, and endothelin (ET levels and a lower nitric oxide (NO level than the control and SCH+T4 groups. The tail and carotid artery blood pressures, left ventricular systolic pressure, heart rate and aorta ventralis blood flow were significantly lower in the SCH group than in the control and SCH+T4 groups. ACH treatment caused concentration-dependent relaxation, which was reduced in the SCH arteries compared with the control and SCH+T4 arteries. Histopathological examination revealed the absence of pathological changes in the SCH rat arteries.These findings demonstrate that L-T4 treatment ameliorates endothelial dysfunction and hemodynamic changes in SCH rats.

  15. In vivo efficacy of SM-8668 (Sch 39304), a new oral triazole antifungal agent.

    Science.gov (United States)

    Tanio, T; Ichise, K; Nakajima, T; Okuda, T

    1990-06-01

    SM-8668 (Sch 39304) is a new oral antifungal agent which we evaluated in comparison with fluconazole in various fungal infection models. The prophylactic effect of SM-8668 was excellent against systemic candidiasis, aspergillosis, and cryptococcosis in mice. The 50% effective dose for SM-8668 was assessed at 10 days after infection and was 0.18, 3.7, and 5.9 mg/kg (body weight), respectively, for the above-mentioned fungal diseases. Fluconazole was about four times less effective than SM-8668 against systemic candidiasis and was only slightly effective at doses of 80 and 25 mg/kg against systemic aspergilosis and cryptococcosis, respectively. SM-8668 was also about four to eight times more active than fluconazole against vaginal candidiasis in rats and against dermatophytic infection in guinea pigs. In addition, topical SM-8668 was as effective as topical miconazole or tioconazole against skin mycosis in guinea pigs. After oral administration, SM-8668 showed a maximum concentration in serum similar to that of fluconazole in both mice and rats, but the elimination half-life and area under the serum concentration-time curve for SM-8668 were twice those for fluconazole.

  16. Engineered Nickel Oxide Nanoparticle Causes Substantial Physicochemical Perturbation in Plants

    Directory of Open Access Journals (Sweden)

    Indrani Manna

    2017-11-01

    Full Text Available Concentration of engineered nickel oxide nanoparticle (NiO-NP in nature is on the rise, owing to large scale industrial uses, which have accreted the scope of its exposure to plants, the primary producers of the ecosystem. Though an essential micronutrient for the animal system, supported by numerous studies confirming its toxicity at higher dosages, nickel oxide is graded as a human carcinogen by WHO. A few studies do depict toxicity and bioaccumulation of nickel in plants; however, interaction of NiO-NP with plants is not well-elucidated. It is known that exposure to NiO-NP can incite stress response, leading to cytotoxicity and growth retardation in some plants, but a defined work on the intricate physicochemical cellular responses and genotoxic challenges is wanting. The present study was planned to explore cytotoxicity of NiO-NP in the model plant, Allium cepa L., its internalization in the tissue and concomitant furore created in the antioxidant enzyme system of the plant. The prospect of the NiO-NP causing genotoxicity was also investigated. Detailed assessments biochemical profiles and genotoxicity potential of NiO-NP on A. cepa L. was performed and extended to four of its closest economically important relatives, Allium sativum L., Allium schoenoprasum L., Allium porrum L., and Allium fistulosum L. Growing root tips were treated with seven different concentrations of NiO-NP suspension (10–500 mg L−1, with deionised distilled water as negative control and 0.4 mM EMS solution as positive control. Study of genotoxic endpoints, like, mitotic indices (MI, chromosomal aberrations (CAs, and chromosome breaks confirmed NiO-NP induced genotoxicity in plants, even at a very low dose (10 mg L−1. That NiO-NP also perturbs biochemical homeostasis, disrupting normal physiology of the cell, was confirmed through changes in state of lipid peroxidation malonaldehyde (MDA, as well as, in oxidation marker enzymes, like catalase (CAT, super oxide

  17. Palinotaxonomia de Albertinia brasiliensis Spreng., Eremanthus bicolor (DC. Baker e Vanillosmopsis erythropappa (DC. Sch. Bip. (Compositae-Vernonieae Palynotaxonomy of Albertinia brasiliensis Spreng., Eremanthus bicolor (DC. Baker and Vanillosmopsis erythropappa (DC. Sch. Bip. (Compositae-Vernonieae

    Directory of Open Access Journals (Sweden)

    Aliny Férras Peçanha

    2008-06-01

    Full Text Available Vanillosmopsis Sch. Bip. tem sido, tradicionalmente, aceito como sinônimo de Eremanthus Less. e o gênero Albertinia Spreng. foi estabelecido para abrigar Albertinia brasiliensis Spreng. O presente trabalho propõe a caracterização polínica de Albertinia brasiliensis, Vanillosmopsis erythropappa e Eremanthus bicolor e fornece subsídios para futuros estudos taxonômicos. Foram utilizados grãos de pólen de espécimens coletados em diferentes herbários. As duas primeiras espécies são encontradas no Rio de Janeiro enquanto Eremanthus Less. não. Assim, optou-se por utilizar a espécie-tipo do gênero na análise polínica. Os grãos de pólen foram acetolisados, medidos, descritos e ilustrados usando microscopia de luz. Grãos de pólen não acetolisados foram usados para análise em microscopia eletrônica de varredura. O resultado do estudo polínico mostrou que as espécies podem ser separadas utilizandose, principalmente, as características das aberturas e da ornamentação da exina e revelou uma gradação evolutiva interespecífica dos caracteres polínicos. Com relação à taxonomia das espécies estudadas, os dados palinológicos comprovam a posição taxonômica de Albertinia brasiliensis, porém não reforça a sinonimização de Vanillosmopsis em Eremanthus.Vanillosmopsis Sch. Bip. has been traditionally accepted as a synonym of Eremanthus Less., and Albertinia Spreng. was established to include Albertinia brasiliensis Spreng. This paper characterizes the pollen of Albertinia brasiliensis, Vanillosmopsis erythropappa and Eremanthus bicolor and provides information for future taxonomic studies. Pollen grains of specimens collected in different herbaria were used in this study. The two first species are found in Rio de Janeiro, but Eremanthus is not found in this state. For this reason, the type species of this genus was used for pollen analysis. Pollen grains were acetolysed, measured, described and illustrated using optical

  18. Nina Degele: Gender/Queer Studies. München: UTB Fink 2008. — Franziska Schößler: Einführung in die Gender Studies. Berlin: Akademie Verlag 2008

    Directory of Open Access Journals (Sweden)

    Heike Kahlert

    2009-03-01

    Full Text Available Nina Degele und Franziska Schößler treiben mit ihren Einführungsbüchern in die Gender Studies beziehungsweise in die Gender/Queer Studies die Disziplinierung dieser neuen Wissensfelder voran. Ausgehend von ihren jeweiligen Herkunftsdisziplinen (Soziologie und Literaturwissenschaft legen sie übersichtliche Überblicke vor, die explizit für die Hochschullehre konzipiert sind. Beide Bücher leisten einen wichtigen Beitrag zur Kanonisierung der Gender Studies als akademisches Fach, bleiben aber in ihrer Konzeption stark den Herkunftsdisziplinen ihrer Verfasserinnen verhaftet. Hier stößt die viel beschworene Interdisziplinarität der Gender Studies an ihre Grenzen.Nina Degele and Franziska Schößler promote the disciplinary establishment of new fields of knowledge with their introductory books in Gender Studies and Gender/Queer Studies. Using their individual home disciplines (sociology and literary studies as a starting point, they present clear overviews of these new fields of knowledge explicitly conceived for use in higher education. Both books contribute to the canonization of Gender Studies as an academic discipline, however they remain in their conception strongly attached to the home disciplines of their authors. It is here that the often-touted interdisciplinarity of Gender Studies reaches its limits.

  19. Alfred Schütz: do referencial teórico-filosófico aos princípios metodológicos de pesquisa fenomenológica

    OpenAIRE

    Zeferino,Maria Terezinha; Carraro,Telma Elisa

    2013-01-01

    Se trata de una reflexión sobre el referencial teórico-filosófico de la sociología fenomenológica, presentando los principios metodológicos de la investigación de Alfred Schütz, entendiendo que este referencial permite la composición completa de la investigación fenomenológica. Cada principio es presentado detalladamente usando la investigación que condujo a la propuesta como referencia, ejemplificando la forma en que fueron trabajadas las etapas para lograr una actitud fenomenológica. Se per...

  20. The Evolution of Juvenile Schönlein-Henoch Purpura

    Directory of Open Access Journals (Sweden)

    O.E. Chernyshova

    2016-10-01

    Full Text Available Background. Hemorrhagic vasculitis, or Schönlein-Henoch purpura (SHP, is the most common type of systemic vasculitis in childhood, and peculiarities of the further evolution of the pathological process in adult patients remain unexplored. Objective: to study the evolution of juvenile SHP, comparing the nature of lesions of the skin, joints, heart and kidneys in patients in childhood and adulthood. Material and methods. The study included 92 patients (61 men and 31 women with the average age of 27 years, and the average age of disease onset — 11 years. I degree of the activity of the pathological process is determined in 40 % of cases, II — in 35 %, III — in 25 %. Seropositivity by hyperimmunoglobulinemia A occurred in 27 % of cases, by the presence of rheumatoid factor — in 21 %. At the time of the survey, cutaneous syndrome was diagnosed in 55 % of patients, joint one — in 45 %, kidney one — in 71 %. Renal biopsy was performed in 15 cases. Results. The cutaneous, cutaneous-joint-abdominal and cutaneous-abdominal-renal forms of the disease, lesions of the skin, gastrointestinal tract, wrist, ankle and knee joints become rarer in the process of juvenile SHP evolution, but exceptionally renal variant of the pathological process, changes of skeletal muscles, liver, spleen and the heart are revealed more often, chronic kidney disease with the renal failure progression is developed in 12 % of patients (in 17 % of cases of nephropathy, sacroiliitis, spondylopathy, tendovaginitis, enthesopathies, epiphyseal osteoporosis and meniscitis of the knee joints are arisen, II, III, VI and IV morphological classes of Henoch glomerulonephritis are formed in a ratio of 8 : 4 : 2 : 1 with tubulointerstitial component in all cases, and lymphohistiocytic infiltration of the vascular wall is the unfavorable sign for the prognosis of the disease. Conclusions. In cases of transition of juvenile SHP into the chronic adult form, the disease often obtain

  1. 34 CFR 692.41 - What standards may a State use to determine substantial financial need?

    Science.gov (United States)

    2010-07-01

    ... PARTNERSHIP PROGRAM Leveraging Educational Assistance Partnership Program How Does A State Select Students... establishes that are approved by the Secretary. A State may define substantial financial need in terms of... “independent student” as defined under section 480(d) of the HEA. However, for good cause shown, the Secretary...

  2. Chewing Prevents Stress-Induced Hippocampal LTD Formation and Anxiety-Related Behaviors: A Possible Role of the Dopaminergic System

    Science.gov (United States)

    Koizumi, So; Onozuka, Minoru

    2015-01-01

    The present study examined the effects of chewing on stress-induced long-term depression (LTD) and anxiogenic behavior. Experiments were performed in adult male rats under three conditions: restraint stress condition, voluntary chewing condition during stress, and control condition without any treatments except handling. Chewing ameliorated LTD development in the hippocampal CA1 region. It also counteracted the stress-suppressed number of entries to the center region of the open field when they were tested immediately, 30 min, or 60 min after restraint. At the latter two poststress time periods, chewing during restraint significantly increased the number of times of open arm entries in the elevated plus maze, when compared with those without chewing. The in vivo microdialysis further revealed that extracellular dopamine concentration in the ventral hippocampus, which is involved in anxiety-related behavior, was significantly greater in chewing rats than in those without chewing from 30 to 105 min after stress exposure. Development of LTD and anxiolytic effects ameliorated by chewing were counteracted by administering the D1 dopamine receptor antagonist SCH23390, which suggested that chewing may activate the dopaminergic system in the ventral hippocampus to suppress stress-induced anxiogenic behavior. PMID:26075223

  3. Chewing prevents stress-induced hippocampal LTD formation and anxiety-related behaviors: a possible role of the dopaminergic system.

    Science.gov (United States)

    Ono, Yumie; Koizumi, So; Onozuka, Minoru

    2015-01-01

    The present study examined the effects of chewing on stress-induced long-term depression (LTD) and anxiogenic behavior. Experiments were performed in adult male rats under three conditions: restraint stress condition, voluntary chewing condition during stress, and control condition without any treatments except handling. Chewing ameliorated LTD development in the hippocampal CA1 region. It also counteracted the stress-suppressed number of entries to the center region of the open field when they were tested immediately, 30 min, or 60 min after restraint. At the latter two poststress time periods, chewing during restraint significantly increased the number of times of open arm entries in the elevated plus maze, when compared with those without chewing. The in vivo microdialysis further revealed that extracellular dopamine concentration in the ventral hippocampus, which is involved in anxiety-related behavior, was significantly greater in chewing rats than in those without chewing from 30 to 105 min after stress exposure. Development of LTD and anxiolytic effects ameliorated by chewing were counteracted by administering the D1 dopamine receptor antagonist SCH23390, which suggested that chewing may activate the dopaminergic system in the ventral hippocampus to suppress stress-induced anxiogenic behavior.

  4. D-2 dopamine receptor activation reduces free [3H]arachidonate release induced by hypophysiotropic peptides in anterior pituitary cells

    International Nuclear Information System (INIS)

    Canonico, P.L.

    1989-01-01

    Dopamine reduces the stimulation of intracellular [ 3 H]arachidonate release produced by the two PRL-stimulating peptides angiotensin-II and TRH. This effect is concentration dependent and is mediated by stimulation of D-2 dopamine receptors. D-2 receptor agonists (bromocriptine, dihydroergocryptine, and dihydroergocristine) inhibit the release of fatty acid induced by angiotensin-II with a potency that parallels their ability to inhibit PRL release in vitro. Conversely, the selective D-2 receptor antagonist L-sulpiride completely prevents dopamine's effect, whereas SCH 23390 (a D-1 receptor antagonist) is ineffective. The inhibitory action of dopamine does not seem to be consequent to an action on the adenylate cyclase-cAMP system, as 8-bromo-cAMP (1 mM) does not affect either basal or dopamine-inhibited [ 3 H]arachidonate release. However, a 24-h pertussis toxin pretreatment significantly reduces the action of dopamine on fatty acid release. Collectively, these results suggest that D-2 dopamine receptor-mediated inhibition of intracellular [ 3 H]arachidonate release requires the action of a GTP-binding protein, but is not a consequence of an inhibitory action on cAMP levels

  5. 20 CFR 604.6 - Conformity and substantial compliance.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Conformity and substantial compliance. 604.6... FOR ELIGIBILITY FOR UNEMPLOYMENT COMPENSATION § 604.6 Conformity and substantial compliance. (a) In... for the administration of its UC program. (b) Resolving Issues of Conformity and Substantial...

  6. 19 CFR 10.7 - Substantial containers or holders.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Substantial containers or holders. 10.7 Section 10... Exported and Returned § 10.7 Substantial containers or holders. (a) Substantial containers or holders... domestic products exported and returned. When such containers or holders are imported not containing or...

  7. Henoch-Schönlein purpura: a long-term prospective study in Greek children.

    Science.gov (United States)

    Fretzayas, Andrew; Sionti, Irini; Moustaki, Maria; Papadimitriou, Anastasios; Nicolaidou, Polyxeni

    2008-12-01

    Henoch-Schönlein purpura is a common vasculitis of childhood. The present study, comprising 74 children enrolled during a 9-year period, aimed to delineate the clinical spectrum and the long term follow-up of the disease. Patients were diagnosed strictly on the criteria established by the American College of Rheumatology. The diagnosis was further strengthened by a skin biopsy performed in more than half of cases (42/74), which revealed leukocytoclastic vasculitis in all patients, whereas IgA deposits were found in 37/42 children. There was a predominance of boys (41 males), and the mean age of study population was 5.2 +/- 2.54 years. Palpable purpura was identified in 73/74 children, whereas transient arthritis manifested in 68/74 children. Gastrointestinal blood loss was elicited in 30 children, 11 of whom had also renal involvement. The latter was seen in 19/74 (25.7%) children, and in the long term follow-up (extended to 2004, from 4-12 years, mean duration 7.3 years), 2 children remained with persistent occult hematuria. Relapses occurred in 49 children (66%), and half of them experienced more than 1 recurrence. Arthritis was less common in the relapsed episodes, and this difference was statistically significant (P period. Recurrences often differ to some extent from the initial episode with arthritis being less common with relapses.

  8. [From Algebra as art to School Algebra : The textbooks written by Pierre de La Ramée, Bernard Salignac and Lazare Schöner].

    Science.gov (United States)

    Loget, François

    2011-01-01

    Bernard Salignac and Lazare Schöner both published a treatise based on La Ramée's Algebra. Why did they endeavour to republish a book that their master had abandoned ? What changes did they make in the original ? They turned algebra into apedagogical discipline at a time when Ramism was making its presence felt in some Northern European educational establishments. Salignac took La Ramée's thoughts concerning the language of mathematics further and offered an original and precocious contribution to what I call the "scriptural turn" of mathematics at the end of the 16(th) century.

  9. Teacher led school-based surveillance can allow accurate tracking of emerging infectious diseases - evidence from serial cross-sectional surveys of febrile respiratory illness during the H1N1 2009 influenza pandemic in Singapore

    Directory of Open Access Journals (Sweden)

    Soh Shu E

    2012-12-01

    the 6 schools (23 to 34 episodes per 100 children, but there was widespread variation by classrooms; in the hierarchical model, omitting age and school effects was inconsequential but neglecting classroom level effects led to highly significant reductions in goodness of fit. Conclusions Epidemic curves from Sch-FRI were comparable to GP-ILI data, and Sch-FRI detected substantially more infections than Sch-LCC and Sch-DTM. Variability in classroom attack rates suggests localized class-room transmission.

  10. Do substantial BMI reduction episodes among Swedish schoolchildren have any impact on their final height?

    Science.gov (United States)

    Nilsen, Bente B; Yngve, Agneta; Werner, Bo

    2018-02-06

    This study investigated whether substantial body mass index (BMI) reductions in Swedish schoolchildren aged seven years to 19 years, caused by disease, healthy or unhealthy behaviour, had any impact on their final height. We used height and weight data on 6572 subjects from two nationally representative longitudinal samples of Swedish children born in 1973 and 1981. These provided information on their final height and any BMI reduction episodes. Of the 6572 subjects (50.9% boys), among individuals with information on final height, 1118 had a BMI reduction of 5% and BMI reduction of 10% or more. On a group level, there was no statistically significant difference in the final height of individuals with BMI reductions of 10% or more and those without. The findings were independent of age and the subject's BMI at the start of the reduction episode. However, there were a number of cases where a substantial BMI reduction probably had an impact on the subject's final height. Our study found no evidence that a substantial BMI reduction had any impact on final height on a group level, but further analyses of specific case studies are necessary to determine whether substantial BMI reduction might have an impact on final height. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  11. Particle reduction strategies - PAREST. Evaluation of emission reduction scenarios using chemical transport calculations. PM10- and NO{sub 2}-immission contributions in Germany. Wood combustion in small combustion systems; installations of the 13th and 17th BImSchV (Federal Immission Control Act). Sub-report.; Strategien zur Verminderung der Feinstaubbelastung - PAREST. Bewertung von Emissionsminderungsszenarien mit Hilfe chemischer Transportberechnungen. PM10- und NO{sub 2}-Immissionsbeitraege in Deutschland. Holzverbrennung in Kleinfeuerungsanlagen, Anlagen der 13. und 17. BImSchV. Teilbericht

    Energy Technology Data Exchange (ETDEWEB)

    Stern, Rainer [Freie Univ. Berlin (Germany). Inst. fuer Meteorologie, Troposphaerische Umweltforschung

    2013-06-15

    This report was prepared within the research project ''Particle reduction strategies - PAREST.'' In this paper with the chemical transport model REM CALGRID following questions were investigated: 1 What is the contribution of the wood-fired small combustion plants in Germany to the PM10- and NO {sub 2}-concentrations? 2 What is the contribution of the 13th and 17th BlmSchV covered installations to the PM10 and NO{sub 2} concentrations in Germany? [German] Der vorliegende Bericht wurde im Rahmen des Forschungs- und Entwicklungsvorhabens ''Strategien zur Verminderung der Feinstaubbelastung'' erstellt. In dem Beitrag werden mit dem chemischen Transportmodell REM-CALGRID folgende Fragestellungen untersucht: 1. Wie hoch ist der Beitrag der mit Holz beheizten Kleinfeuerungsanlagen in Deutschland zu den PM10- und den NO{sub 2}-Konzentrationen? 2. Wie hoch ist der Beitrag der von der 13. und 17. BImSchV erfassten Anlagen zu den PM10-und NO-2-Konzentrationen in Deutschland?.

  12. [Changes in 25-hydroxyvitamin D3 level in children with Henoch-Schönlein purpura].

    Science.gov (United States)

    Zhang, Yuan-Da; Dong, Qing-Wei; Li, Rong-Min; Ji, Chao-Yu; Chu, Yong-Tao; Ma, Lei; Zhang, Yu

    2017-03-01

    To examine the changes in 25-hydroxyvitamin D 3 [25-(OH)D 3 ] level in children with Henoch-Schönlein purpura (HSP) and its clinical significance. A total of 92 HSP children were included in this study, and were divided into HSP nephritis (HSPN) group (31 cases) and HSP group (61 cases) based on the presence or absence of HSPN. Alternatively, the patients were divided into purpura alone group (22 cases), purpura with joint symptoms group (joint symptom group, 24 cases), purpura with gastrointestinal symptoms group (gastrointestinal symptom group, 20 cases), and purpura with joint and gastrointestinal symptoms (mixed group, 26 cases) based on their clinical symptoms. In addition, 42 healthy children were selected as healthy control group. The level of 25-(OH)D 3 in each group was measured using enzyme-linked immunoassay. The 25-(OH)D 3 level in the HSP and HSPN groups was significantly lower than that in the healthy control group (Ppurpura alone group (P<0.05). The level of 25-(OH)D 3 is reduced in children with HSP, particularly those with HSPN or with joint and gastrointestinal symptoms. Therefore, the reduction in 25-(OH)D 3 level may serve as a predictor of whether HSP is associated with other impairments.

  13. Substantial decrease in cell wall α-1,3-glucan caused by disruption of the kexB gene encoding a subtilisin-like processing protease in Aspergillus oryzae.

    Science.gov (United States)

    Mizutani, Osamu; Shiina, Matsuko; Yoshimi, Akira; Sano, Motoaki; Watanabe, Takeshi; Yamagata, Youhei; Nakajima, Tasuku; Gomi, Katsuya; Abe, Keietsu

    2016-09-01

    Disruption of the kexB encoding a subtilisin-like processing protease in Aspergillus oryzae (ΔkexB) leads to substantial morphological defects when the cells are grown on Czapek-Dox agar plates. We previously found that the disruption of kexB causes a constitutive activation of the cell wall integrity pathway. To understand how the disruption of the kexB affects cell wall organization and components, we analyzed the cell wall of ΔkexB grown on the plates. The results revealed that both total N-acetylglucosamine content, which constitutes chitin, and chitin synthase activities were increased. Whereas total glucose content, which constitutes β-1,3-glucan and α-1,3-glucan, was decreased; this decrease was attributed to a remarkable decrease in α-1,3-glucan. Additionally, the β-1,3-glucan in the alkali-insoluble fraction of the ΔkexB showed a high degree of polymerization. These results suggested that the loss of α-1,3-glucan in the ΔkexB was compensated by increases in the chitin content and the average degree of β-1,3-glucan polymerization.

  14. Involvement of monoaminergic systems in anxiolytic and antidepressive activities of the standardized extract of Cocos nucifera L.

    Science.gov (United States)

    Lima, Eliane Brito Cortez; de Sousa, Caren Nádia Soares; Meneses, Lucas Nascimento; E Silva Pereira, Yuri Freitas; Matos, Natália Castelo Branco; de Freitas, Rayanne Brito; Lima, Nycole Brito Cortez; Patrocínio, Manoel Cláudio Azevedo; Leal, Luzia Kalyne Almeida Moreira; Viana, Glauce Socorro Barros; Vasconcelos, Silvânia Maria Mendes

    2017-01-01

    Extracts from the husk fiber of Cocos nucifera are used in folk medicine, but their actions on the central nervous system have not been studied. Here, the anxiolytic and antidepressant effects of the standardized hydroalcoholic extract of C. nucifera husk fiber (HECN) were evaluated. Male Swiss mice were treated with HECN (50, 100, or 200 mg/kg) 60 min before experiments involving the plus maze test, hole-board test, tail suspension test, and forced swimming test (FST). HECN was administered orally (p.o.) in acute and repeated-dose treatments. The forced swimming test was performed with dopaminergic and noradrenergic antagonists, as well as a serotonin release inhibitor. Administration of HECN in the FST after intraperitoneal (i.p.) pretreatment of mice with sulpiride (50 mg/kg), prazosin (1 mg/kg), or p-chlorophenylalanine (PCPA, 100 mg/kg) caused the actions of these three agents to be reversed. However, this effect was not observed after pretreating the animals with SCH23390 (15 µg/kg, i.p.) or yohimbine (1 mg/kg, i.p.) The dose chosen for HECN was 100 mg/kg, p.o., which increased the number of entries as well as the permanence in the open arms of the maze after acute and repeated doses. In both the forced swimming and the tail suspension tests, the same dose decreased the time spent immobile but did not disturb locomotor activity in an open-field test. The anxiolytic effect of HECN appears to be related to the GABAergic system, while its antidepressant effect depends upon its interaction with the serotoninergic, noradrenergic (α1 receptors), and dopaminergic (D2 dopamine receptors) systems.

  15. Basolateral amygdalar D2 receptor activation is required for the companions-exerted suppressive effect on the cocaine conditioning.

    Science.gov (United States)

    Tzeng, Wen-Yu; Cherng, Chian-Fang G; Yu, Lung; Wang, Ching-Yi

    2017-01-01

    The presence of companions renders decreases in cocaine-stimulated dopamine release in the nucleus accumbens and cocaine-induced conditioned place preference (CPP) magnitude. Limbic systems are widely believed to underlie the modulation of accumbal dopamine release and cocaine conditioning. Thus, this study aimed to assess whether intact basolateral nucleus of amygdala (BLA), dorsal hippocampus (DH), and dorsolateral striatum (DLS) is required for the companions-exerted suppressive effect on the cocaine-induced CPP. Three cage mates, serving as companions, were arranged to house with the experimental mice in the cocaine conditioning compartment throughout the cocaine conditioning sessions. Approximately 1week before the conditioning procedure, intracranial ibotenic acid infusions were done in an attempt to cause excitotoxic lesions targeting bilateral BLA, DH and DLS. Albeit their BLA, DH, and DLS lesions, the lesioned mice exhibited comparable cocaine-induced CPP magnitudes compared to the intact and sham lesion controls. Bilateral BLA, but not DH or DLS, lesions abolished the companions-exerted suppressive effect on the cocaine-induced CPP. Intact mice receiving intra-BLA infusion of raclopride, a selective D2 antagonist, 30min prior to the cocaine conditioning did not exhibit the companions-exerted suppressive effect on the cocaine-induced CPP. Intra-BLA infusion of Sch23390, a selective D1 antagonist, did not affect the companions-exerted suppressive effect on the CPP. These results, taken together, prompt us to conclude that the intactness of BLA is required for the companions-exerted suppressive effect on the cocaine-induced CPP. Importantly, activation of D2 receptor in the BLA is required for such suppressive effect on the CPP. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Net-Zero Building Technologies Create Substantial Energy Savings -

    Science.gov (United States)

    only an estimated 1% of commercial buildings are built to net-zero energy criteria. One reason for this Continuum Magazine | NREL Net-Zero Building Technologies Create Substantial Energy Savings Net -Zero Building Technologies Create Substantial Energy Savings Researchers work to package and share step

  17. Chronic and acute adenosine A2A receptor blockade prevents long-term episodic memory disruption caused by acute cannabinoid CB1 receptor activation.

    Science.gov (United States)

    Mouro, Francisco M; Batalha, Vânia L; Ferreira, Diana G; Coelho, Joana E; Baqi, Younis; Müller, Christa E; Lopes, Luísa V; Ribeiro, Joaquim A; Sebastião, Ana M

    2017-05-01

    Cannabinoid-mediated memory impairment is a concern in cannabinoid-based therapies. Caffeine exacerbates cannabinoid CB 1 receptor (CB 1 R)-induced memory deficits through an adenosine A 1 receptor-mediated mechanism. We now evaluated how chronic or acute blockade of adenosine A 2A receptors (A 2A Rs) affects long-term episodic memory deficits induced by a single injection of a selective CB 1 R agonist. Long-term episodic memory was assessed by the novel object recognition (NOR) test. Mice received an intraperitoneal (i.p.) injection of the CB 1 /CB 2 receptor agonist WIN 55,212-2 (1 mg/kg) immediately after the NOR training, being tested for novelty recognition 24 h later. Anxiety levels were assessed by the Elevated Plus Maze test, immediately after the NOR. Mice were also tested for exploratory behaviour at the Open Field. For chronic A 2A R blockade, KW-6002 (istradefylline) (3 mg/kg/day) was administered orally for 30 days; acute blockade of A 2A Rs was assessed by i.p. injection of SCH 58261 (1 mg/kg) administered either together with WIN 55,212-2 or only 30 min before the NOR test phase. The involvement of CB 1 Rs was assessed by using the CB 1 R antagonist, AM251 (3 mg/kg, i.p.). WIN 55,212-2 caused a disruption in NOR, an action absent in mice also receiving AM251, KW-6002 or SCH 58261 during the encoding/consolidation phase; SCH 58251 was ineffective if present during retrieval only. No effects were detected in the Elevated Plus maze or Open Field Test. The finding that CB 1 R-mediated memory disruption is prevented by antagonism of adenosine A 2A Rs, highlights a possibility to prevent cognitive side effects when therapeutic application of CB 1 R drugs is desired. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Risk Factors Associated with Renal Involvement in Childhood Henoch-Schönlein Purpura: A Meta-Analysis

    Science.gov (United States)

    Chan, Han; Tang, Yan-Ling; Lv, Xiao-Hang; Zhang, Gao-Fu; Wang, Mo; Yang, Hai-Ping; Li, Qiu

    2016-01-01

    Background and objective Henoch-Schönlein purpura (HSP) is an important cause of chronic kidney disease in children. This meta-analysis identified risk factors associated with renal involvement in childhood HSP. Methods PubMed, Embase, and Web of Science were searched. The quality of all eligible studies was assessed using the Newcastle-Ottawa scale criteria. An analysis of possible risk factors was conducted to report the odds ratio (OR) and weighted mean difference (WMD). Results Thirteen studies (2398 children) revealed 20 possible and 13 significant risk factors associated with renal involvement in HSP, with the following meta-analysis estimates of OR and WMD, with 95% confidence intervals: older age (0.90, 0.61–1.19); age > 10 y (3.13, 1.39–7.07); male gender (1.36, 1.07–1.74); abdominal pain (1.94,1.24–3.04); gastrointestinal bleeding (1.86, 1.30–2.65); severe bowel angina (3.38, 1.17–9.80); persistent purpura (4.02, 1.22–13.25); relapse (4.70, 2.42–9.14); WBC > 15 × 109/L (2.42, 1.39–4.22); platelets > 500 × 109/L (2.98, 1.22–7.25); elevated antistreptolysin O (ASO) (2.17, 1.29–3.64); and decreased complement component 3 (C3) (3.13, 1.62–6.05). Factors not significantly associated with renal involvement were: blood pressure; orchitis; elevated C-reactive protein; elevated erythrocyte sedimentation rate (ESR); and elevated serum IgA/IgE or IgG. Arthritis/arthralgia may be a risk factor according to the criteria of the American College of Rheumatology (1.41, 1.01–1.96). Conclusion The following are associated with renal involvement in pediatric HSP: male gender; > 10 y old; severe gastrointestinal symptoms (abdominal pain, gastrointestinal bleeding, and severe bowel angina); arthritis/arthralgia; persistent purpura or relapse; WBC > 15 × 109/L; platelets > 500 × 109/L; elevated ASO; and low C3. Relevant clinical interventions for these risk factors may exert positive effects on the prevention of kidney disease during the early

  19. Excessive anticoagulation with warfarin or phenprocoumon may have multiple causes

    DEFF Research Database (Denmark)

    Meegaard, Peter Martin; Holck, Line H V; Pottegård, Anton

    2012-01-01

    Excessive anticoagulation with vitamin K antagonists is a serious condition with a substantial risk of an adverse outcome. We thus found it of interest to review a large case series to characterize the underlying causes of excessive anticoagulation.......Excessive anticoagulation with vitamin K antagonists is a serious condition with a substantial risk of an adverse outcome. We thus found it of interest to review a large case series to characterize the underlying causes of excessive anticoagulation....

  20. Blocking Dopaminergic Signaling Soon after Learning Impairs Memory Consolidation in Guinea Pigs.

    Directory of Open Access Journals (Sweden)

    Kiera-Nicole Lee

    Full Text Available Formation of episodic memories (i.e. remembered experiences requires a process called consolidation which involves communication between the neocortex and hippocampus. However, the neuromodulatory mechanisms underlying this neocortico-hippocampal communication are poorly understood. Here, we examined the involvement of dopamine D1 receptors (D1R and D2 receptors (D2R mediated signaling on memory consolidation using the Novel Object Recognition (NOR test. We conducted the tests in male Hartley guinea pigs and cognitive behaviors were assessed in customized Phenotyper home cages utilizing Ethovision XT software from Noldus enabled for the 3-point detection system (nose, center of the body, and rear. We found that acute intraperitoneal injections of either 0.25 mg/kg SCH23390 to block D1Rs or 1.0 mg/kg sulpiride to block D2Rs soon after acquisition (which involved familiarization to two similar objects attenuated subsequent discrimination for novel objects when tested after 5-hours in the NOR test. By contrast guinea pigs treated with saline showed robust discrimination for novel objects indicating normal operational processes undergirding memory consolidation. The data suggests that involvement of dopaminergic signaling is a key post-acquisition factor in modulating memory consolidation in guinea pigs.

  1. Dopamine antagonists during parturition disrupt maternal care and the retention of maternal behavior in rats.

    Science.gov (United States)

    Byrnes, Elizabeth M; Rigero, Beth A; Bridges, Robert S

    2002-11-01

    Brief contact with pups at parturition enables the female rat to establish and retain the full repertoire of maternal behaviors, allowing her to respond rapidly to pups in the future. To determine whether the dopamine system is involved in the retention of maternal behavior, females were continuously infused with dopamine antagonists during the periparturitional period and then allowed either a brief interaction period with pups (3 h) or no interaction with pups (pups removed as they were born). Females were exposed to either the D1-like antagonist SCH 23390 (0.1 or 1.0 mg/kg/day) or the D2-like antagonist clebopride (0.5 or 1.0 mg/kg/day). The high dose of either DA antagonist resulted in significant attenuation of maternal care immediately postpartum. When tested for the retention of maternal behavior 7 days later, however, only the females exposed to the D2 antagonist displayed a delayed response to shown full maternal behavior (FMB) towards donor pups. Thus, while both dopamine receptor subtypes appear necessary for the full and rapid expression of maternal behavior during the early postpartum period, only the D2 receptor subtype appears to be involved in the retention of this behavior.

  2. Developmental plasticity in the D1- and D2-mediation of motor behavior in rats depleted of dopamine as neonates.

    Science.gov (United States)

    Byrnes, E M; Ughrin, Y; Bruno, J P

    1996-12-01

    D1- and D2-like antagonist-induced catalepsy and dorsal immobility were studied in pups (Day 10) and weanlings (Days 20, 28, or 35) that received intraventricular injection of 6-OHDA (50 micrograms/hemisphere) or its vehicle solution or postnatal Day 3. The ability of the D1 of D2 antagonists to induce immobility differed as a function of the lesion condition and the age at the time of testing. Moreover, the two behavioral measures exhibited differences in their specific D1 and D2 receptor modulation. Administration of the D1 antagonist SCH 23390 (0.2 or 1.0 mg/kg) or the D2 antagonist clebopride (1.0, 10.0, or 20.0 mg/kg) led to catalepsy and dorsal immobility in intact rats, regardless of test age. Both antagonists induced catalepsy and dorsal immobility in rats depleted of DA when tested on Day 10. However, the effects of each antagonist in DA-depleted rats were ether negligible or significantly less than in controls when animals were tested as weanlings. These data suggest lesion-induced changes in the DA receptor modulation of motor behavior and that this plasticity requires more than a week to become apparent.

  3. Chewing Prevents Stress-Induced Hippocampal LTD Formation and Anxiety-Related Behaviors: A Possible Role of the Dopaminergic System

    Directory of Open Access Journals (Sweden)

    Yumie Ono

    2015-01-01

    Full Text Available The present study examined the effects of chewing on stress-induced long-term depression (LTD and anxiogenic behavior. Experiments were performed in adult male rats under three conditions: restraint stress condition, voluntary chewing condition during stress, and control condition without any treatments except handling. Chewing ameliorated LTD development in the hippocampal CA1 region. It also counteracted the stress-suppressed number of entries to the center region of the open field when they were tested immediately, 30 min, or 60 min after restraint. At the latter two poststress time periods, chewing during restraint significantly increased the number of times of open arm entries in the elevated plus maze, when compared with those without chewing. The in vivo microdialysis further revealed that extracellular dopamine concentration in the ventral hippocampus, which is involved in anxiety-related behavior, was significantly greater in chewing rats than in those without chewing from 30 to 105 min after stress exposure. Development of LTD and anxiolytic effects ameliorated by chewing were counteracted by administering the D1 dopamine receptor antagonist SCH23390, which suggested that chewing may activate the dopaminergic system in the ventral hippocampus to suppress stress-induced anxiogenic behavior.

  4. In vitro and in vivo evaluation of [123I]IBZM: a potential CNS D-2 dopamine receptor imaging agent

    International Nuclear Information System (INIS)

    Kung, H.F.; Pan, S.; Kung, M.P.; Billings, J.; Kasliwal, R.; Reilley, J.; Alavi, A.

    1989-01-01

    In vitro binding characteristics of a CNS dopamine D-2 receptor imaging agent, (S)-N-[(1-ethyl-2-pyrrolidinyl)] methyl-2-hydroxy-3-iodo-6-methoxybenzamide [( 125 I]IBZM), was carried out in rats. Also brain images, as well as organ biodistribution were determined in a monkey following the administration of 123 I-labeled compound. The S-(-)-I[ 125 I]IBZM showed high specific dopamine D-2 receptor binding in rat striatum (Kd = 0.426 +/- 0.082 nM, Bmax = 480 +/- 22 fmol/mg of protein). Competition of various ligands for the IBZM binding displayed the following rank order of potency: spiperone greater than S(-)IBZM much greater than R(+)IBZM greater than or equal to S(-)BZM greater than dopamine greater than ketanserin greater than SCH-23390 much greater than propranolol, norepinephrine, serotonin. In vivo planar images of a monkey injected with [ 123 I]IBZM demonstrated a high concentration in basal ganglia of brain. The ratios of activity in the basal ganglia to cerebellum and the cortex to cerebellum in monkey brain were 4.93 and 1.44, respectively, at 120 min postinjection. These preliminary results indicate that [ 123 I]IBZM is a potentially promising imaging agent for the investigation of dopamine D-2 receptors in humans

  5. Development of specific dopamine D-1 agonists and antagonists

    International Nuclear Information System (INIS)

    Sakolchai, S.

    1987-01-01

    To develop potentially selective dopamine D-1 agonists and to investigate on the structural requirement for D-1 activity, the derivatives of dibenzocycloheptadiene are synthesized and pharmacologically evaluated. The target compounds are 5-aminomethyl-10,11-dihydro-1,2-dihydroxy-5H-dibenzo[a,d]cycloheptene hydrobromide 10 and 9,10-dihydroxy-1,2,3,7,8,12b-hexahydrobenzo[1,2]cyclohepta[3,4,5d,e]isoquinoline hydrobromide 11. In a dopamine-sensitive rat retinal adenylate cyclase assay, a model for D-1 activity, compound 10 is essentially inert for both agonist and antagonist activity. In contrast, compound 11 is approximately equipotent to dopamine in activation of the D-1 receptor. Based on radioligand and binding data, IC 50 of compound 11 for displacement of 3 H-SCH 23390, a D-1 ligand, is about 7 fold less than that for displacement of 3 H-spiperone, a D-2 ligand. These data indicate that compound 11 is a potent selective dopamine D-1 agonist. This study provides a new structural class of dopamine D-1 acting agent: dihydroxy-benzocycloheptadiene analog which can serve as a lead compound for further drug development and as a probe for investigation on the nature of dopamine D-1 receptor

  6. Dopamine inhibits lipopolysaccharide-induced nitric oxide production through the formation of dopamine quinone in murine microglia BV-2 cells

    Directory of Open Access Journals (Sweden)

    Yasuhiro Yoshioka

    2016-02-01

    Full Text Available Dopamine (DA has been suggested to modulate functions of glial cells including microglial cells. To reveal the regulatory role of DA in microglial function, in the present study, we investigated the effect of DA on lipopolysaccharide (LPS-induced nitric oxide (NO production in murine microglial cell line BV-2. Pretreatment with DA for 24 h concentration-dependently attenuated LPS-induced NO production in BV-2 cells. The inhibitory effect of DA on LPS-induced NO production was not inhibited by SCH-23390 and sulpiride, D1-like and D2-like DA receptor antagonists, respectively. In addition, pretreatment with (−-(6aR,12bR-4,6,6a,7,8,12b-Hexahydro-7-methylindolo[4,3-a]phenanthridin (CY 208–243 and bromocriptine, D1-like and D2-like DA receptor agonists, respectively, did not affect the LPS-induced NO production. N-Acetylcysteine, which inhibits DA oxidation, completely inhibited the effect of DA. Tyrosinase, which catalyzes the oxidation of DA to DA quionone (DAQ, accelerated the inhibitory effect of DA on LPS-induced NO production. These results suggest that DA attenuates LPS-induced NO production through the formation of DAQ in BV-2 cells.

  7. Use of waste fuels in cement works. Application of the 17th Ordinance for the Protection against Nuisances (BImSchV) to plants for baking cement clinkers; Einsatz von Sonderbrennstoffen in Zementwerken. Anwendung der 17. BlmSchV auf Anlagen zum Brennen von Zementklinker

    Energy Technology Data Exchange (ETDEWEB)

    Mair, K. [Bayerisches Landesamt fuer Umweltschutz, Muenchen (Germany)

    1995-06-01

    In cement works, other fuels besides the regular ones - coal, heavy fuel and natural gas - are used. Burning these materials requires proper handling and must correspond to state-of-the-art practices, especially as regards clean air measures. The ordinance on fire-places for wastes and other fuel materials (17th ordinance for the protection against nuisances) contains not only relevant emission limits but makes also stipulations as to the design of fire-places, emission monitoring, and general rules. (orig.) [Deutsch] In der Zementindustrie werden neben den sogenannten Regelbrennstoffen wie Kohle, Heizoel S und Erdgas auch Sonderbrennstoffe eingesetzt. Der Einsatz dieser Stoffe setzt jedoch eine ordnungsgemaesse Handhabung bei gleichzeitiger Einhaltung der dem Stand der Technik entsprechenden Massnahmen, besonders zur Luftreinhaltung, voraus. In der Verordnung ueber Verbrennungsanlagen fuer Abfaelle und aehnliche brennbare Stoffe (17. BlmSchV) werden hierzu neben den Emissionsbegrenzungen auch Anforderungen an die Beschaffenheit der Feuerungen, die Emissionsueberwachung sowie allgemeine Regelungen vorgegeben. (orig.)

  8. 20 CFR 654.13 - Determination of areas of substantial unemployment.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Determination of areas of substantial unemployment. 654.13 Section 654.13 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF... 10582 § 654.13 Determination of areas of substantial unemployment. An area of substantial unemployment...

  9. [Henoch-Schönlein purpura in a cocaine consumer man with HIV infection and ANCA-p positivity].

    Science.gov (United States)

    De Paoli, María C; Moretti, Dino; Scolari Pasinato, Carlos M; Buncuga, Martín G

    The Henoch-Schönlein purpura (HSP) is a small vessel vasculitis with IgA immune complex deposition. The presentation in adults is rare and severe. Reported cases of HSP in patients infected with HIV are scarce. Neutrophil cytoplasmic antibodies (ANCA) are commonly found in other systemic vasculitis, but rarely in HSP and even more unusual the perinuclear pattern. Beside small vessel vasculitis, positivity of ANCA can be detected in a number of different pathological conditions in association with infectious processes, including HIV, or cocaine use, and especially the pattern of ANCA-p, associated with drugs, inflammatory bowel or autoimmune diseases. We report the case of a 35 years old man with toxic habits (cocaine, marijuana) who consulted for abdominal pain, hematochezia and purpura on lower extremities, and later fever, joint pain and progression of purpura associated with nephritic syndrome and ANCA-p (+). During hospitalization HIV infection was detected. Renal biopsy showed IgA nephropathy with favorable response to corticosteroid and antiproteinuric treatment. The communication of the case is due to the rarity of the presentation and therapeutic diagnostic challenge. It remains to elucidate the role of ANCA in the pathogenesis and management of adult PSH.

  10. The Poitiers School of Mathematical and Theoretical Biology: Besson-Gavaudan-Schützenberger's Conjectures on Genetic Code and RNA Structures.

    Science.gov (United States)

    Demongeot, J; Hazgui, H

    2016-12-01

    The French school of theoretical biology has been mainly initiated in Poitiers during the sixties by scientists like J. Besson, G. Bouligand, P. Gavaudan, M. P. Schützenberger and R. Thom, launching many new research domains on the fractal dimension, the combinatorial properties of the genetic code and related amino-acids as well as on the genetic regulation of the biological processes. Presently, the biological science knows that RNA molecules are often involved in the regulation of complex genetic networks as effectors, e.g., activators (small RNAs as transcription factors), inhibitors (micro-RNAs) or hybrids (circular RNAs). Examples of such networks will be given showing that (1) there exist RNA "relics" that have played an important role during evolution and have survived in many genomes, whose probability distribution of their sub-sequences is quantified by the Shannon entropy, and (2) the robustness of the dynamics of the networks they regulate can be characterized by the Kolmogorov-Sinaï dynamic entropy and attractor entropy.

  11. Hepatocyte-based in vitro model for assessment of drug-induced cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, Sagnik, E-mail: Sagnik.Chatterjee@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium); Richert, Lysiane, E-mail: l.richert@kaly-cell.com [KaLy-Cell, 20A rue du Général Leclerc, 67115 Plobsheim (France); Augustijns, Patrick, E-mail: Patrick.Augustijns@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium); Annaert, Pieter, E-mail: Pieter.Annaert@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium)

    2014-01-01

    Early detection of drug-induced cholestasis remains a challenge during drug development. We have developed and validated a biorelevant sandwich-cultured hepatocytes- (SCH) based model that can identify compounds causing cholestasis by altering bile acid disposition. Human and rat SCH were exposed (24–48 h) to known cholestatic and/or hepatotoxic compounds, in the presence or in the absence of a concentrated mixture of bile acids (BAs). Urea assay was used to assess (compromised) hepatocyte functionality at the end of the incubations. The cholestatic potential of the compounds was expressed by calculating a drug-induced cholestasis index (DICI), reflecting the relative residual urea formation by hepatocytes co-incubated with BAs and test compound as compared to hepatocytes treated with test compound alone. Compounds with clinical reports of cholestasis, including cyclosporin A, troglitazone, chlorpromazine, bosentan, ticlopidine, ritonavir, and midecamycin showed enhanced toxicity in the presence of BAs (DICI ≤ 0.8) for at least one of the tested concentrations. In contrast, the in vitro toxicity of compounds causing hepatotoxicity by other mechanisms (including diclofenac, valproic acid, amiodarone and acetaminophen), remained unchanged in the presence of BAs. A safety margin (SM) for drug-induced cholestasis was calculated as the ratio of lowest in vitro concentration for which was DICI ≤ 0.8, to the reported mean peak therapeutic plasma concentration. SM values obtained in human SCH correlated well with reported % incidence of clinical drug-induced cholestasis, while no correlation was observed in rat SCH. This in vitro model enables early identification of drug candidates causing cholestasis by disturbed BA handling. - Highlights: • Novel in vitro assay to detect drug-induced cholestasis • Rat and human sandwich-cultured hepatocytes (SCH) as in vitro models • Cholestatic compounds sensitize SCH to toxic effects of accumulating bile acids • Drug

  12. Hepatocyte-based in vitro model for assessment of drug-induced cholestasis

    International Nuclear Information System (INIS)

    Chatterjee, Sagnik; Richert, Lysiane; Augustijns, Patrick; Annaert, Pieter

    2014-01-01

    Early detection of drug-induced cholestasis remains a challenge during drug development. We have developed and validated a biorelevant sandwich-cultured hepatocytes- (SCH) based model that can identify compounds causing cholestasis by altering bile acid disposition. Human and rat SCH were exposed (24–48 h) to known cholestatic and/or hepatotoxic compounds, in the presence or in the absence of a concentrated mixture of bile acids (BAs). Urea assay was used to assess (compromised) hepatocyte functionality at the end of the incubations. The cholestatic potential of the compounds was expressed by calculating a drug-induced cholestasis index (DICI), reflecting the relative residual urea formation by hepatocytes co-incubated with BAs and test compound as compared to hepatocytes treated with test compound alone. Compounds with clinical reports of cholestasis, including cyclosporin A, troglitazone, chlorpromazine, bosentan, ticlopidine, ritonavir, and midecamycin showed enhanced toxicity in the presence of BAs (DICI ≤ 0.8) for at least one of the tested concentrations. In contrast, the in vitro toxicity of compounds causing hepatotoxicity by other mechanisms (including diclofenac, valproic acid, amiodarone and acetaminophen), remained unchanged in the presence of BAs. A safety margin (SM) for drug-induced cholestasis was calculated as the ratio of lowest in vitro concentration for which was DICI ≤ 0.8, to the reported mean peak therapeutic plasma concentration. SM values obtained in human SCH correlated well with reported % incidence of clinical drug-induced cholestasis, while no correlation was observed in rat SCH. This in vitro model enables early identification of drug candidates causing cholestasis by disturbed BA handling. - Highlights: • Novel in vitro assay to detect drug-induced cholestasis • Rat and human sandwich-cultured hepatocytes (SCH) as in vitro models • Cholestatic compounds sensitize SCH to toxic effects of accumulating bile acids • Drug

  13. Chemical Composition of the Essential Oils of the Flowers, Leaves and Stems of Two Senecio polyanthemoides Sch. Bip. Samples from South Africa

    Directory of Open Access Journals (Sweden)

    Lawal A. Oladipupo

    2009-06-01

    Full Text Available The essential oils of the flowers, leaves and stems of Senecio polyanthemoides Sch. Bip. Samples collected from two different localities within the city of uMhlathuze, KwaZulu-Natal Province (South Africa were isolated by hydrodistillation and analyzed using GC and GC/MS. Twenty-six constituents were identified, representing an average of 86.0 - 99.6% of the total oil composition. The chemical profile reveals the dominance of monoterpenoid compounds, although some quantitative variance was noticed. The main constituents of the oils were limonene (3.1 – 43.0%, p-cymene (4.9-36.3%, β-selinene (1.3-32.7%, α-pinene (1.8-21.4%, β-pinene (7.6-16.5% and 1,8-cineole (9.3-11.4%, caryophyllene oxide (4.1-13.4% and humulene epoxide II (8.6-10.3%.

  14. Comprometimento de estruturas encefálicas não hipotalâmicas na moléstia de Hand-Schüller-Christian: relato de caso e revisão da literatura

    Directory of Open Access Journals (Sweden)

    José Geraldo Camargo Lima

    1975-06-01

    Full Text Available É relatado um caso de moléstia de Hand-Schüller-Christian que, além de elementos da tríade clássica e retração concêntrica do campo visual, apresentava uma síndrome piramidal. A raridade do comprometimento de estruturas encefálicas não hipotalâmicas nessa moléstia é realçada. É enfatizada a ação benéfica da corticoterapia e radioterapia observada no caso.

  15. Subclinical hypothyroidism: Controversies to consensus

    Directory of Open Access Journals (Sweden)

    Syed Abbas Raza

    2013-01-01

    Full Text Available Diagnoses of subclinicaal hypothyroidism (SCH is biochemically made, when serum thyroid stimulating hormone (TSH levels is elevated while free thyroid hormone levels are within normal reference range. SCH is diagnosed after excluding all other causes of elevated TSH levels. Symptoms of SCH may vary from being asymptomatic to having mild nonspecific symptoms. The risk of progression to overt hypothyroidism is related to number of factors including initial serum TSH concentration, presence of auto antibodies, family history and presence goiter. Various screening recommendations for thyroid function assessment are in practice. There are still controversies surrounding SCH and associated risk of various cardiovascular diseases (CVDs, pregnancy outcomes, neuropsychiatric issues, metabolic syndrome, and dyslipidemia. Consensus will require more large randomized clinical studies involving various age groups and medical condition, especially in developing countries. All these efforts will definitely improve our understanding of disease and ultimately patient outcomes.

  16. Les bases moléculaires et cellulaires de la protection conférée par l’antagoniste du récepteur D1 de la dopamine, SCH23390, contre les effets toxiques de la méthamphétamine dans le cerveau de rat

    OpenAIRE

    Beauvais , Geneviève

    2012-01-01

    Methamphetamine (METH) is a potent psychostimulant known to cause cognitive abnormalities and neurodegenerative changes in the brains of METH abusers. One approach for developing therapies for METH abuse is to understand the molecular mechanisms of toxicity of the drug. Investigations in our laboratory and elsewhere have shown that single intraperitoneal injections of METH (30-40 mg/kg of body weight) can cause damage to striatal and cortical monoaminergic systems and induce neuronal apoptosi...

  17. A dirty cause of vancomycin-mediated Henoch-Schonlein purpura: oxygen tubing is not a foley.

    Science.gov (United States)

    Shah, Nikhil H; Kline, Kristopher P; Shukla, Manas K

    2017-06-20

    A 59-year-old male presented with methicillin-resistant Staphylococcus aureus bacteraemia from a prostatic abscess and was treated with vancomycin. Two weeks into his treatment course, he developed severe joint pains, abdominal pain with bloody, mucinous stools and a diffuse palpable purpuric rash on his extremities. Biopsy of the rash showed IgA immune-complex deposition consistent with Henoch-Schönlein purpura. After treatment with glucocorticoids, his symptoms resolved completely. Vancomycin is an extremely commonly used antibiotic with certain well-known adverse effects. Henoch-Schönlein purpura, a vasculitis involving abdominal pain, arthralgias and palpable purpura, is a much less common side effect, as seen in this patient. Given that vancomycin is widely used internationally, clinicians should be aware of the risks entailed by its use. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Increased greenhouse effect substantiated through measurements

    International Nuclear Information System (INIS)

    Skartveit, Arvid

    2001-01-01

    The article presents studies on the greenhouse effect which substantiates the results from satellite measurements during the period 1970 - 1997. These show an increased effect due to increase in the concentration of the climatic gases CO 2 , methane, CFC-11 and CFC-12 in the atmosphere

  19. Successful Prednisolone Therapy in Elderly Patients with Severe Forms of Henoch–Schönlein Purpura Nephritis

    Directory of Open Access Journals (Sweden)

    Saiko Kato-Okada

    2015-01-01

    Full Text Available Introduction Recently, Henoch–Schönlein purpura (HSP has been observed in elderly people, although it was believed to be uncommon in these subjects. The increased risks of developing end-stage renal disease (ESRD in adults in comparison with children were highlighted by different studies; however, limited data are available on the treatment of HSP nephritis in adults. Methods Between 2002 and 2008, five elderly Japanese patients (>65 years old (mean age, 68 years, ranging from 65 to 72 with severe forms of HSP nephritis were entered into a prospective study to evaluate prednisolone therapy on the outcome of nephropathy in terms of clinical symptoms and histopathological changes. The patients were considered at risk of developing chronic renal failure when they presented with a nephrotic syndrome and crescentic glomeruli. Results At the last follow-up, 4–10 years after initiation of the therapy, four patients had clinically recovered and one died of lung cancer. No patients developed ESRD. The clinical outcome seemed to be correlated with glomerular activity (massive proteinuria and crescent formation. In spite of a relatively large dose of prednisolone, a few adverse effects, such as insomnia and skin lesions, were observed. Discussion Our preliminary small study suggests that renal outcome as well as survival of elderly patients with severe forms of HSP might be altered by aggressive prednisolone therapy.

  20. 19 CFR 134.35 - Articles substantially changed by manufacture.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Articles substantially changed by manufacture. 134... substantially changed by manufacture. (a) Articles other than goods of a NAFTA country. An article used in the United States in manufacture which results in an article having a name, character, or use differing from...

  1. The use of geographic information system as a tool for schistosomiasis surveillance in the province of Davao del Norte, the Philippines

    Directory of Open Access Journals (Sweden)

    Vicente Y. Belizario

    2017-11-01

    Full Text Available Schistosomiasis (SCH in The Philippines is caused by Schistosoma japonicum and remains endemic in 28 provinces in 12 regions. Effective SCH control requires describing areas at risk where control efforts may be focused. This study aims at demonstrating the utility of geographical information system (GIS as a tool for SCH surveillance in the province of Davao del Norte. Qualitative and quantitative data on SCH determinants, obtained from local government offices, partner agencies and institutions, were standardised, formatted and incorporated into a GIS map. Atrisk areas are described in terms of determinants and (variables, which included geography and climate (topography, temperature and flood-prone areas, agriculture (irrigation and land use, poverty (percentage of households with income below the poverty threshold, sanitation level (percentage of households with sanitary toilets, intermediate and reservoir hosts (presence of snail colonies and reservoir hosts as well as prevalence and treatment coverage. Endemic villages (barangays were generally found to be located in flood-prone areas in the lowlands near major rivers. New Corella has the highest poverty index among the SCH-endemic areas studied as well as the highest number of confirmed snail colonies. Among known endemic localities in Davao del Norte, Tagum City was found to be the only city meeting the poverty index target of <16.6%. Clustering of SCH cases were reported in six barangays ranging from 0.48% (8 out of 1,655 in Braulio Dujali to 2% (25 out of 1,405 in Asuncion. This study demonstrates the utility of GIS in predicting and assessing SCH risk, which allows prioritisation and allocation of control resources and delivery of services in areas at the highest risk for SCH.

  2. Popular Science and Apocalyptic Narrative in Frank Schätzing’s The Swarm

    Directory of Open Access Journals (Sweden)

    Gabriele Dürbeck

    2012-01-01

    Full Text Available This paper analyses the use of the rhetoric of the Apocalypse and the concept of nature's revenge in Frank Schätzing's eco-thriller The Swarm. Ecocritical research has identified these narrative patterns as characteristic of contemporary environmental literature. In The Swarm, the apocalyptical rhetoric fulfils the double function of providing thrill and pleasure to the readers and warning them about imminent environmental peril, thereby combining conventions from the two genres of eco-thriller and science fiction. Contrasting reviews have described the novel as either enlightening or pseudo-religious. This ambivalence is the effect of various strategies employed to popularise scientific knowledge in the novel. The narrative embraces various scientific fields, for example the depiction of a network in contrast to swarm theory. The key conflict in the story embodies conflicting concepts of nature - anthropocentric vs. eco-systemic - which are represented by two contrasting groups of characters: one aiming to extinguish the alien superorganism that attacks the human race, the other aspiring to integrate the alien organism into the human world and propagating a holistic view of the Earth. The concepts of a 'tragic' and a 'comical apocalypse' correspond to the double closure which first features a show-down, the annihilation of the 'bad' characters, and then, in the epilogue, a warning message delivered by a 'good' character which confirms - in contrast to, for example, Michael Crichton's State of Fear - the ongoing environmental crisis. Although the epilogue extensively appeals to the human ability to rethink attitudes towards nature, the novel's support for environmental concerns is limited, not only because this message remains rather abstract but also because the vision of a reconciled, pseudo-religious ecosystem as a holistic superorganism has a highly ambivalent meaning for humanity.

  3. D1 receptors regulate dendritic morphology in normal and stressed prelimbic cortex.

    Science.gov (United States)

    Lin, Grant L; Borders, Candace B; Lundewall, Leslie J; Wellman, Cara L

    2015-01-01

    Both stress and dysfunction of prefrontal cortex are linked to psychological disorders, and structure and function of medial prefrontal cortex (mPFC) are altered by stress. Chronic restraint stress causes dendritic retraction in the prelimbic region (PL) of mPFC in rats. Dopamine release in mPFC increases during stress, and chronic administration of dopaminergic agonists results in dendritic remodeling. Thus, stress-induced alterations in dopaminergic transmission in PL may contribute to dendritic remodeling. We examined the effects of dopamine D1 receptor (D1R) blockade in PL during daily restraint stress on dendritic morphology in PL. Rats either underwent daily restraint stress (3h/day, 10 days) or remained unstressed. In each group, rats received daily infusions of either the D1R antagonist SCH23390 or vehicle into PL prior to restraint; unstressed and stressed rats that had not undergone surgery were also examined. On the final day of restraint, rats were euthanized and brains were processed for Golgi histology. Pyramidal neurons in PL were reconstructed and dendritic morphology was quantified. Vehicle-infused stressed rats demonstrated dendritic retraction compared to unstressed rats, and D1R blockade in PL prevented this effect. Moreover, in unstressed rats, D1R blockade produced dendritic retraction. These effects were not due to attenuation of the HPA axis response to acute stress: plasma corticosterone levels in a separate group of rats that underwent acute restraint stress with or without D1R blockade were not significantly different. These findings indicate that dopaminergic transmission in mPFC during stress contributes directly to the stress-induced retraction of apical dendrites, while dopamine transmission in the absence of stress is important in maintaining normal dendritic morphology. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. D1 and D2 antagonists reverse the effects of appetite suppressants on weight loss, food intake, locomotion, and rebalance spiking inhibition in the rat NAc shell

    Science.gov (United States)

    Kalyanasundar, B.; Perez, Claudia I.; Luna, Alvaro; Solorio, Jessica; Moreno, Mario G.; Elias, David; Simon, Sidney A.

    2015-01-01

    Obesity is a worldwide health problem that has reached epidemic proportions. To ameliorate this problem, one approach is the use of appetite suppressants. These compounds are frequently amphetamine congeners such as diethylpropion (DEP), phentermine (PHEN), and bupropion (BUP), whose effects are mediated through serotonin, norepinephrine, and dopaminergic pathways. The nucleus accumbens (NAc) shell receives dopaminergic inputs and is involved in feeding and motor activity. However, little is known about how appetite suppressants modulate its activity. Therefore, we characterized behavioral and neuronal NAc shell responses to short-term treatments of DEP, PHEN, and BUP. These compounds caused a transient decrease in weight and food intake while increasing locomotion, stereotypy, and insomnia. They evoked a large inhibitory imbalance in NAc shell spiking activity that correlated with the onset of locomotion and stereotypy. Analysis of the local field potentials (LFPs) showed that all three drugs modulated beta, theta, and delta oscillations. These oscillations do not reflect an aversive-malaise brain state, as ascertained from taste aversion experiments, but tracked both the initial decrease in weight and food intake and the subsequent tolerance to these drugs. Importantly, the appetite suppressant-induced weight loss and locomotion were markedly reduced by intragastric (and intra-NAc shell) infusions of dopamine antagonists SCH-23390 (D1 receptor) or raclopride (D2 receptor). Furthermore, both antagonists attenuated appetite suppressant-induced LFP oscillations and partially restored the imbalance in NAc shell activity. These data reveal that appetite suppressant-induced behavioral and neuronal activity recorded in the NAc shell depend, to various extents, on dopaminergic activation and thus point to an important role for D1/D2-like receptors (in the NAc shell) in the mechanism of action for these anorexic compounds. PMID:25972577

  5. 21 CFR 514.4 - Substantial evidence.

    Science.gov (United States)

    2010-04-01

    ... adequate and well-controlled studies, such as a study in a target species, study in laboratory animals... and conditions of use. Substantial evidence of effectiveness of a new animal drug shall demonstrate that the new animal drug is effective for each intended use and associated conditions of use for and...

  6. Morphological substantiation for acute immobilization stress-related disorders of adaptation mechanisms.

    Science.gov (United States)

    Koptev, Mykhailo M; Vynnyk, Nataliia I

    Nowadays, an individual is being constantly accompanied by stresses in his/her everyday life. Stress reactions, produced in the process of evolution, have become the organisms' response to emergency action or pathological factors and are the important link in adaptation process. However, the adverse course of stress reaction can lead to derangement of the adaptation mechanisms in the body and become the element of the pathogenesis of various diseases. The study was aimed at morphological substantiation of derangement of adaptation mechanisms in white Wistar rats caused by the acute immobilization stress. 40 Wistar white male rats of 240-260 g body weight aged 8-10 months were involved into study. 20 laboratory animals were assigned to the main group and the rest 20 rats formed the control (II) group. Experimental stress model was simulated by immobilization of rats, lying supine, for 6 hours. Morphological examination of heart, lungs and kidneys was carried out after animals' decapitation, which proved the derangement of rats' adaptation mechanisms caused by the acute immobilization stress. It has been established that six-hour immobility of rats, lying in the supine position, led to the development of destructive phenomena, hemorrhagic lesions and impaired hemomicrocirculation. Microscopically, the acute immobilization stress causes significant subendocardial hemorrhages, plethora of vessels of hemomicrocirculatory flow with dysdiemorrhysis, myocardial intersticium edema in the heart. Histologically, immobilization-induced trauma causes significant hemodynamic disorders, spasm of arterioles and considerable venous hyperemia, concomitant with microthrombosis in kidneys; at the same time dystrophic lesions and desquamation of epithelium of renal tubules has been observed in renal corpuscles. The abovementioned structural changes can contribute to origination and development of multiple lesions, demonstrating the morphologically grounded role of the acute

  7. Henoch-Schönlein purpura in adults: a case series from a multidisciplinary study group Púrpura de Henoch-Schönlein em adultos: uma série de casos de um grupo de estudo multidisciplinar

    Directory of Open Access Journals (Sweden)

    Boris A. Cruz

    2006-12-01

    Full Text Available BACKGROUND: Henoch-Schönlein purpura (HSP is a systemic vasculitis involving small vessels with the deposition of immune complexes containing IgA. It has been extensively studied in children, but in adults, its natural history is much less known. OBJECTIVES: to report a series of patients with HSP presenting in their adulthood. PATIENTS AND METHODS: the Minas Gerais Vasculitis Study Group´s Members (MGVSG were invited to report patients with HSP who appeared in their adulthood. A standardized retrospective chart review was done. RESULTS: eleven patients, two male and nine female, age 39.4 +/- 20.1 yearsold were studied. Nine patients presented purpura, seven presented arthritis, four patients had gastrointestinal involvement and ten patients (91% presented glomerulonephritis (GN. Eight patients were subjected to renal biopsies. Six of them presented endocapillary proliferative GN and only two of them had minimal mesangial proliferation. In the other three patients, HSP was confirmed by skin biopsies. All patients received steroids, in five of them steroids were combined with other immunosuppressive agents. After a follow-up of 39.0 +/- 64.6 months, four patients (36% presented impairment of renal function, but only one (9% developed end stage renal disease and was successfully appeared to renal transplantation. At the end of follow-up, seven patients (64% are in complete remission and four in partial remission. CONCLUSION: in adulthood, HSP represents a distinct clinical syndrome with a higher frequency of renal involvement and more severe systemic vasculitis. Nevertheless, the final outcome in this series was as good as reported in children, maybe due to aggressive immunosuppressive therapy.INTRODUÇÃO: púrpura de Henoch-Schönlein (PHS é uma vasculite sistêmica que acomete vasos de pequeno calibre com depósitos de imunocomplexos contendo IgA. Esta vasculite já foi extensamente estudada em crianças, mas sua história natural em adultos

  8. The profile of adult onset Henoch-Schönlein purpura in an Asian population.

    Science.gov (United States)

    Yong, Adeline Mei-Yen; Lee, Shan-Xian; Tay, Yong-Kwang

    2015-11-01

    Henoch-Schönlein purpura (HSP) is less common in adults and has been linked with a more severe clinical syndrome as well as a higher frequency of renal disease and internal malignancy. Renal involvement in adult HSP has been significantly associated with antecedent infections, pyrexia at time of first presentation, and purpura above the waist. We aim to evaluate the frequency of cutaneous and extra-cutaneous features and identify the predictive factors for renal involvement in Asian adults with HSP. We performed a retrospective study of 48 adult Asian patients diagnosed with HSP based on the European League Against Rheumatism (EULAR) criteria at a tertiary hospital in Singapore between January 2000 and December 2011. The most common cutaneous manifestations were palpable purpura (73%), papules (31%), and petechiae (27%). Forty-percent had cutaneous lesions extending above the waist. Fifteen patients (31%) had gastrointestinal symptoms, 21 (44%) had joint involvement, and 27 (56%) had renal disease. Seventy-percent of patients with pyrexia at presentation experienced renal disease, whereas only 30% without pyrexia had renal involvement (P = 0.018). Sixty-six percent of patients with purpura had renal involvement as compared to 31% in those without purpura (P = 0.049). The frequency of renal involvement in patients with purpura above the waist (52%) was similar to those with purpura below the waist (55%). Our study confirms that HSP in adults tends to be more severe with a high incidence of extracutaneous manifestations, especially renal disease. Pyrexia at presentation and the presence of purpura were significant predictive factors for renal involvement. © 2015 The International Society of Dermatology.

  9. A mountain river sediment cascade and its controls: the Schöttlbach torrent, Styria

    Science.gov (United States)

    Lutzmann, Silke; Stangl, Johannes; Sass, Oliver

    2017-04-01

    Steep alpine headwater torrents are characterized by episodic heavy floods and bedload pulses triggered by local high-intensity mountain rainstorms. They frequently pose serious risks and damage in the densely populated East Alpine Region. It is important to understand where critical sediments are mobilized, how much bedload is delivered to the outlet and what controls the variability. We present a concept to quantify the sediment cascade's components and influencing factors for the Schöttlbach torrent - a 71 km2 non-glaciated catchment in the Niedere Tauern mountain Range in Styria, Austria. Geomorphic mapping is used to identify primary bedload sources on slope as well as patterns of lithology, slope-channel coupling and vegetation conditioning erosion intensity. We apply modern near-range measuring techniques (TLS, Structure from Motion) to monitor erosion rates from representative erosion sites and sediment delivery rates at the outlet since 2014. These measurements are interpreted based on the geomorphic map to derive a catchment-wide seasonal sediment budget. To explain seasonal variations we evaluate precipitation and discharge data from a dense station network as storm precipitation and runoff events are the main triggers of torrent sediment mobilization. Torrent reaches in instable glaciofluvial sediments of the last glaciation show high average erosion rates of ca. 0.08 m/a from 2014 to 2016 surpassing rates in deeply weathered bedrock reaches by an order of magnitude (approx. 0.006 m/a). We model a torrent-wide erosion volume of 2000 m3/a opposing an output of 7000 m3/a in that period. We attribute parts of this discrepancy to a sediment wave reworking signal of an extreme flood event in 2011.

  10. Methodology for substantiation of the fast reactor fuel element serviceability

    International Nuclear Information System (INIS)

    Tsykanov, V.A.; Maershin, A.A.

    1988-01-01

    Methodological aspects of fast reactor fuel element serviceability substantiation are presented. The choice of the experimental program and strategies of its realization to solve the problem set in short time, taking into account available experimental means, are substantiated. Factors determining fuel element serviceability depending on parameters and operational conditions are considered. The methodological approach recommending separate studing of the factors, which points to the possibility of data acquisition, required for the development of calculational models and substantiation of fuel element serviceability in pilot and experimental reactors, is described. It is shown that the special-purpose data are more useful for the substantiation of fuel element serviceability and analytical method development than unsubstantial and expensive complex tests of fuel elements and fuel assemblies, which should be conducted only at final stages for the improvement of the structure on the whole

  11. Association of ACE, VEGF and CCL2 gene polymorphisms with Henoch-Schönlein purpura and an evaluation of the possible interaction effects of these loci in HSP patients.

    Science.gov (United States)

    Mohammadian, Tahereh; Bonyadi, Mortaza; Nabat, Elahe; Rafeey, Mandana

    2017-07-01

    Henoch-Schönlein purpura (HSP) is a multisystem, small vessel, leucocytoclastic vasculitis. It is predominantly a childhood vasculitis, rarely reported in adults. Studies have shown that several different genetic factors such as genes involved in inflammatory system and renin-angiotensin system (RAS) are important in the pathogenesis of Henoch-Schönlein purpura. The purpose of this study was to evaluate the independent effect of 3 gene polymorphisms including CCL2-2518 C/T, VEGF-634G/C and ACE(I/D) with HSP disease and their possible joint interactions in developing the disease. In this case-control study 47 HSP cases and 74 unrelated healthy controls were enrolled for evaluation. All individuals were genotyped for CCL2-2518C/T, VEGF-634G/C and ACE(I/D) gene polymorphisms. The possible association of these polymorphisms with susceptibility to develop HSP disease independently and in different joint combinations was evaluated. The frequencies of TT genotype and T allele of CCL2-2518C/T gene polymorphism and CC genotype and C allele of VEGF-634G/C gene polymorphism were significantly high in HSP children (p-values = 0.005 and = 0.007 respectively). Interestingly, studying the joint interaction of these 2 genotypes (CC genotype of VEGF G-634C and TT genotype of CCL2 C-2518T) in this cohort showed a more significant effect in the development of the disease (p gene when combined with II genotype of ACE gene in HSP children was significantly higher (p gene-gene interaction effects of CCL2, VEGF and ACE genes in developing HSP disease.

  12. Establishing Substantial Equivalence: Proteomics

    Science.gov (United States)

    Lovegrove, Alison; Salt, Louise; Shewry, Peter R.

    Wheat is a major crop in world agriculture and is consumed after processing into a range of food products. It is therefore of great importance to determine the consequences (intended and unintended) of transgenesis in wheat and whether genetically modified lines are substantially equivalent to those produced by conventional plant breeding. Proteomic analysis is one of several approaches which can be used to address these questions. Two-dimensional PAGE (2D PAGE) remains the most widely available method for proteomic analysis, but is notoriously difficult to reproduce between laboratories. We therefore describe methods which have been developed as standard operating procedures in our laboratory to ensure the reproducibility of proteomic analyses of wheat using 2D PAGE analysis of grain proteins.

  13. From Pingcheng to Luoyang-Substantiation of the climatic cause for capital relocation of the Beiwei Dynasty

    Institute of Scientific and Technical Information of China (English)

    HSU Shengi

    2004-01-01

    Emperor Tuoba Hong1) of Beiwei relocated the capital from Pingcheng to Luoyang approximately 1500 years ago. Most historians speculate that his motivation was based on considerations of politics, economics, military, history, and Chinese culture. However, Sima Guang, a famous historian during the Song Dynasty, claimed 1000 years ago that cold climate was the cause of this historical event. In order to assess the credibility of Sima Guang's claim, this research examines related ancient documents and the recent frost data for a comparative study. It is found that the mean minimum temperature in Pingcheng during 479AD~509AD is estimated to be lower than present minimum temperature by 2.48 ℃.

  14. Adenosine A{sub 2A} receptor imaging with [{sup 11}C]KF18446 PET in the rat brain after quinolinic acid lesion. Comparison with the dopamine receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ishiwata, Kiichi; Ogi, Nobuo; Hayakawa, Nobutaka [Tokyo Metropolitan Inst. of Gerontology, Tokyo (Japan). Positron Medical Center] [and others

    2002-11-01

    We proposed [{sup 11}C]KF18446 as a selective radioligand for mapping the adenosine A{sub 2A} receptors being highly enriched in the striatum by positron emission tomography (PET). In the present study, we investigated whether [{sup 11}C]KF18446 PET can detect the change in the striatal adenosine A{sub 2A} receptors in the rat after unilateral injection of an excitotoxin quinolinic acid into the striatum, a Huntington's disease model, to demonstrate the usefulness of [{sup 11}C]KF18446. The extent of the striatal lesion was identified based on MRI, to which the PET was co-registered. The binding potential of [{sup 11}C]KF18446 significantly decreased in the quinolinic acid-lesioned striatum. The decrease was comparable to the decrease in the potential of [{sup 11}C] raclopride binding to dopamine D{sub 2} receptors in the lesioned striatum, but seemed to be larger than the decrease in the potential of [{sup 11}C]SCH23390 binding to dopamine D{sub 1} receptors. Ex vivo and in vitro autoradiography validated the PET signals. We concluded that [{sup 11}C]KF18446 PET can detect change in the adenosine A{sub 2A} receptors in the rat model, and will provide a new diagnostic tool for characterizing post-synaptic striatopallidal neurons in the stratum. (author)

  15. Infralimbic dopamine D2 receptors mediate glucocorticoid-induced facilitation of auditory fear memory extinction in rats.

    Science.gov (United States)

    Dadkhah, Masoumeh; Abdullahi, Payman Raise; Rashidy-Pour, Ali; Sameni, Hamid Reza; Vafaei, Abbas Ali

    2018-03-01

    The infralimbic (IL) cortex of the medial prefrontal cortex plays an important role in the extinction of fear memory. Also, it has been showed that both brain glucocorticoid and dopamine receptors are involved in many processes such as fear extinction that drive learning and memory; however, the interaction of these receptors in the IL cortex remains unclear. We examined a putative interaction between the effects of glucocorticoid and dopamine receptors stimulation in the IL cortex on fear memory extinction in an auditory fear conditioning paradigm in male rats. Corticosterone (the endogenous glucocorticoid receptor ligand), or RU38486 (the synthetic glucocorticoid receptor antagonist) microinfusion into the IL cortex 10 min before test 1 attenuated auditory fear expression at tests 1-3, suggesting as an enhancement of fear extinction. The effect of corticosterone, but not RU38486 was counteracted by the dopamine D2 receptor antagonist sulpiride pre-treatment administered into the IL (at a dose that failed to alter freezing behavior on its own). In contrast, intra-IL infusion of the dopamine D1 receptor antagonist SCH23390 pre-treatment failed to alter freezing behavior. These findings provide evidence for the involvement of the IL cortex D2 receptors in CORT-induced facilitation of fear memory extinction. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Development of uncoupling between D1- and D2-mediated motor behavior in rats depleted of dopamine as neonates.

    Science.gov (United States)

    Byrnes, E M; Bruno, J P

    1994-09-01

    The D1- and D2-mediation of stimulated motor behavior was studied in pups (Days 10-11) and weanlings (Days 20-21) that had been depleted of dopamine (DA) on postnatal Day 3. Administration of the D1-like agonist SKF 38393 (30.0 mg/kg) or the D2-like agonist quinpirole (3.0 mg/kg) increased the incidence of sniffing and locomotion in intact and DA-depleted animals tested at either age. However, the ability of selective DA antagonists to reduce these stimulated responses interacted with both the depletion and the age at the time of testing. When tested as pups, both the D1 antagonist SCH 23390 (0.2 or 0.4 mg/kg) and the D2 antagonist clebopride (10.0 mg/kg) suppressed the behaviors induced by either class of DA agonist. When tested as weanlings, intact animals exhibited the profile of pups (i.e., either antagonist blocked each agonist). In DA-depleted weanlings, however, only the D1 antagonist blocked the D1 agonist-induced responses and only the D2 antagonist blocked the D2 agonist-induced responses. These data demonstrate that the interactions between D1 and D2 receptors in the expression of stimulated motor behaviors are altered following DA depletions in neonates. Moreover, this change in receptor function occurs sometime between 7 and 13 days after the DA depletion.

  17. Dopamine D1 and D2 dopamine receptors regulate immobilization stress-induced activation of the hypothalamus-pituitary-adrenal axis.

    Science.gov (United States)

    Belda, Xavier; Armario, Antonio

    2009-10-01

    Whereas the role of most biogenic amines in the control of the hypothalamus-pituitary-adrenal (HPA) response to stress has been extensively studied, the role of dopamine has not. We studied the effect of different dopamine receptor antagonists on HPA response to a severe stressor (immobilization, IMO) in adult male Sprague-Dawley rats. Haloperidol administration reduced adrenocorticotropin hormone and corticosterone responses to acute IMO, particularly during the post-IMO period. This effect cannot be explained by a role of dopamine to maintain a sustained activation of the HPA axis as haloperidol did not modify the response to prolonged (up to 6 h) IMO. Administration of more selective D1 and D2 receptor antagonists (SCH23390 and eticlopride, respectively) also resulted in lower and/or shorter lasting HPA response to IMO. Dopamine, acting through both D1 and D2 receptors, exerts a stimulatory role on the activation of the HPA axis in response to a severe stressor. The finding that dopamine is involved in the maintenance of post-stress activation of the HPA axis is potentially important because the actual pathological impact of HPA activation is likely to be related to the area under the curve of plasma glucocorticoid levels, which is critically dependent on how long after stress high levels of glucocorticoid are maintained.

  18. Antidepressant-Like Effects of Sanggenon G, Isolated from the Root Bark of Morus alba, in Rats: Involvement of the Serotonergic System.

    Science.gov (United States)

    Lim, Dong Wook; Jung, Jae-Woo; Park, Ji-Hae; Baek, Nam-In; Kim, Yun Tai; Kim, In-Ho; Han, Daeseok

    2015-01-01

    The root bark of Morus alba is commonly used as an alternative medicine due to its numerous health benefits in humans. However, the antidepressant effects of various active components from M. alba have not been fully elucidated. In this study, we aimed to determine whether sanggenon G, an active compound isolated from the root bark of M. alba, exhibited antidepressant-like activity in rats subjected to forced swim test (FST)-induced depression. Acute treatment of rats with sanggenon G (30 mg/kg, intraperitoneally (i.p.)) significantly reduced immobility time and increased swimming time without any significant change in climbing. Rats treated with sanggenon G also exhibited a decrease in the limbic hypothalamic-pituitary-adrenal (HPA) axis response to the FST, as indicated by attenuation of the corticosterone response and decreased c-Fos immunoreactivity in the hypothalamic paraventricular nucleus (PVN). In addition, the antidepressant-like effects of sanggenon G were significantly inhibited by WAY100635 (1 mg/kg, i.p.; a selective 5-hydroxytryptamine1A (5-HT1A) receptor antagonist), but not SCH23390 (0.05 mg/kg, i.p.; a dopamine D1 receptor antagonist). Our findings suggested that the antidepressant-like effects of sanggenon G were mediated by an interaction with the serotonergic system. Further studies are needed to evaluate the potential of sanggenon G as an alternative therapeutic approach for the treatment of depression.

  19. [A study on toxic effects of sodium salicylate on rat cochlear spiral ganglion neurons: dopamine receptors mediate expressions of NMDA and GABAA receptors].

    Science.gov (United States)

    Wei, Ting-Jia; Chen, Hui-Ying; Huang, Xi; Weng, Jing-Jin; Qin, Jiang-Yuan; Su, Ji-Ping

    2017-06-25

    The aim of the present study was to observe whether dopamine receptor (DR) was involved in the effects of sodium salicylate (SS) on the expressions of N-methyl-D-aspartic acid (NMDA) and γ-aminobutyric acid (GABA) receptors in rat cochlear spiral ganglion neurons (SGNs). Forty-eight hours after primary culture of rat SGNs, immunofluorescence technique was applied to detect expressions of DR1 and DR2, the two subtypes of dopamine receptors. Western blot was performed to assess NMDA receptor NR1 subunit and GABA A receptor subunit α2 (GABRα2) protein expressions in the SGNs after the treatments of SS alone or in combination with DR antagonists. The results demonstrated that: (1) The DR1 and DR2 were expressed in the bodies and axons of the SGN; (2) After the treatment with SS, the surface protein expressions of GABRα2 and NR1 were decreased by 44.69% and 21.57%, respectively, while the total protein expressions showed no significant changes; (3) Neither SS + SCH23390 (DR1 antagonist) group nor SS + Eticlopride (DR2 antagonist) group showed significant differences in GABRα2 and NR1 surface protein expressions compared with the control group. These results suggest that SS regulates the surface GABA A and NMDA receptors trafficking on SGN, and the mechanism may involve DR mediation.

  20. Dissociable Hippocampal and Amygdalar D1-like receptor contribution to Discriminated Pavlovian conditioned approach learning

    Science.gov (United States)

    Andrzejewski, Matthew E; Ryals, Curtis

    2016-01-01

    Pavlovian conditioning is an elementary form of reward-related behavioral adaptation. The mesolimbic dopamine system is widely considered to mediate critical aspects of reward-related learning. For example, initial acquisition of positively-reinforced operant behavior requires dopamine (DA) D1 receptor (D1R) activation in the basolateral amygdala (BLA), central nucleus of the amygdala (CeA), and the ventral subiculum (vSUB). However, the role of D1R activation in these areas on appetitive, non-drug-related, Pavlovian learning is not currently known. In separate experiments, microinfusions of the D1-like receptor antagonist SCH-23390 (3.0 nmol/0.5 μL per side) into the amygdala and subiculum preceded discriminated Pavlovian conditioned approach (dPCA) training sessions. D1-like antagonism in all three structures impaired the acquisition of discriminated approach, but had no effect on performance after conditioning was asymptotic. Moreover, dissociable effects of D1-like antagonism in the three structures on components of discriminated responding were obtained. Lastly, the lack of latent inhibition in drug-treated groups may elucidate the role of D1-like in reward-related Pavlovian conditioning. The present data suggest a role for the D1 receptors in the amygdala and hippocampus in learning the significance of conditional stimuli, but not in the expression of conditional responses. PMID:26632336

  1. Location of skin lesions in Henoch-Schönlein purpura and its association with significant renal involvement.

    Science.gov (United States)

    St John, Jessica; Vedak, Priyanka; Garza-Mayers, Anna Cristina; Hoang, Mai P; Nigwekar, Sagar U; Kroshinsky, Daniela

    2018-01-01

    Henoch-Schönlein purpura (HSP) is a small vessel IgA-predominant vasculitis. To describe adult patients with HSP and determine if the distribution of skin lesions (ie, purpura above the waist or purpura below the waist only), is a predictor of significant renal involvement at the time of the skin biopsy and the months following. A retrospective study on renal function from 72 adult patients with skin-biopsy proven HSP. Longitudinal renal data were analyzed after HSP diagnosis by using baseline renal function for comparison. Statistical analysis adjusted for sex, age, and baseline creatinine revealed a trend between HSP lesions only on the upper and lower extremities and long-term renal involvement (4.767, P = .067). Moreover, in another analysis adjusted for age and baseline creatinine, lesions located only on the upper and lower extremities significantly increased the odds of having long-term significant renal involvement (6.55, P = .049) in men. This retrospective study used patient information that was subject to selection bias. In patients with HSP, skin lesion distribution on the extremities might be predictive of significant long-term renal involvement and might be critical for risk stratification and development of personalized diagnostics and therapeutics. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  2. Low-level APC mutational mosaicism is the underlying cause in a substantial fraction of unexplained colorectal adenomatous polyposis cases.

    Science.gov (United States)

    Spier, Isabel; Drichel, Dmitriy; Kerick, Martin; Kirfel, Jutta; Horpaopan, Sukanya; Laner, Andreas; Holzapfel, Stefanie; Peters, Sophia; Adam, Ronja; Zhao, Bixiao; Becker, Tim; Lifton, Richard P; Perner, Sven; Hoffmann, Per; Kristiansen, Glen; Timmermann, Bernd; Nöthen, Markus M; Holinski-Feder, Elke; Schweiger, Michal R; Aretz, Stefan

    2016-03-01

    In 30-50% of patients with colorectal adenomatous polyposis, no germline mutation in the known genes APC, causing familial adenomatous polyposis, MUTYH, causing MUTYH-associated polyposis, or POLE or POLD1, causing polymerase-proofreading-associated polyposis can be identified, although a hereditary aetiology is likely. This study aimed to explore the impact of APC mutational mosaicism in unexplained polyposis. To comprehensively screen for somatic low-level APC mosaicism, high-coverage next-generation sequencing of the APC gene was performed using DNA from leucocytes and a total of 53 colorectal tumours from 20 unrelated patients with unexplained sporadic adenomatous polyposis. APC mosaicism was assumed if the same loss-of-function APC mutation was present in ≥ 2 anatomically separated colorectal adenomas/carcinomas per patient. All mutations were validated using diverse methods. In 25% (5/20) of patients, somatic mosaicism of a pathogenic APC mutation was identified as underlying cause of the disease. In 2/5 cases, the mosaic level in leucocyte DNA was slightly below the sensitivity threshold of Sanger sequencing; while in 3/5 cases, the allelic fraction was either very low (0.1-1%) or no mutations were detectable. The majority of mosaic mutations were located outside the somatic mutation cluster region of the gene. The present data indicate a high prevalence of pathogenic mosaic APC mutations below the detection thresholds of routine diagnostics in adenomatous polyposis, even if high-coverage sequencing of leucocyte DNA alone is taken into account. This has important implications for both routine work-up and strategies to identify new causative genes in this patient group. 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/

  3. 26 CFR 1.42-7 - Substantially bond-financed buildings. [Reserved

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Substantially bond-financed buildings. [Reserved] 1.42-7 Section 1.42-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY INCOME TAX INCOME TAXES Credits Against Tax § 1.42-7 Substantially bond-financed buildings. [Reserved] ...

  4. Complementary sex determination substantially increases extinction proneness of haplodiploid populations.

    Science.gov (United States)

    Zayed, Amro; Packer, Laurence

    2005-07-26

    The role of genetic factors in extinction is firmly established for diploid organisms, but haplodiploids have been considered immune to genetic load impacts because deleterious alleles are readily purged in haploid males. However, we show that single-locus complementary sex determination ancestral to the haplodiploid Hymenoptera (ants, bees, and wasps) imposes a substantial genetic load through homozygosity at the sex locus that results in the production of inviable or sterile diploid males. Using stochastic modeling, we have discovered that diploid male production (DMP) can initiate a rapid and previously uncharacterized extinction vortex. The extinction rate in haplodiploid populations with DMP is an order of magnitude greater than in its absence under realistic but conservative demographic parameter values. Furthermore, DMP alone can elevate the base extinction risk in haplodiploids by over an order of magnitude higher than that caused by inbreeding depression in threatened diploids. Thus, contrary to previous expectations, haplodiploids are more, rather than less, prone to extinction for genetic reasons. Our findings necessitate a fundamental shift in approaches to the conservation and population biology of these ecologically and economically crucial insects.

  5. Securing and reporting for 2008 and 2010 on the amount and type of VOC emissions from plants in the scope of the 31th BImSchV; Sicherung und Berichterstattung fuer 2008 und 2010 ueber Menge und Art der VOC-Emissionen aus Anlagen im Geltungsbereich der 31.BImSchV

    Energy Technology Data Exchange (ETDEWEB)

    Tebert, Christian; Volz, Susanne [Institut fuer Oekologie und Politik GmbH (OEKOPOL), Hamburg (Germany); Theloke, Jochen [Stuttgart Univ. (DE). Inst. fuer Energiewirtschaft und Rationelle Energieanwendung (IER)

    2011-09-15

    The Directive 1999/13/EC (also called ''VOC-directive'' or ''Solvents Directive'') obliges the Member States of the European Union to a preparation of a report on the implementation of this Directive every three years. The target of a project of the Federal Environment Agency (Dessau-Rosslau, Federal Republic of Germany) is to assist the federal government in meeting the reporting requirements and to relieve the Federal States during data acquisition as possible. For this, an estimation of the CMR material types and quantities of CMR is focused. Recommendations are pronounced to determine the total emissions of VOCs from plants within the scope of the 31th BImSchV (Federal Nuisance Control Ordinance). The research project investigated the requirements for data provision in the individual Federal States and the possibilities for data delivery in addition to a full survey of the Federal States.

  6. Obesity increases the risk of renal involvement in children with Henoch-Schönlein purpura.

    Science.gov (United States)

    Zhao, Yong-Li; Liu, Zheng-Juan; Bai, Xue-Mei; Wang, Yu-Chuan; Li, Guo-Hua; Yan, Xue-Yan

    2015-10-01

    The main aim of this study was to evaluate the relationship between obesity and renal involvement in children with Henoch-Schönlein purpura (HSP). A retrospective study of 141 pediatric patients with HSP was conducted in our hospital. The clinical data of all patients were collected from the electronic medical record management system from January 2010 to June 2014. The possible risk factors of renal involvement, especially obesity, were analyzed using univariate and multivariate analyses. Renal involvement occurred in 45/141 of the patients. A univariate analysis showed that an age more than 7 years at onset, persistent purpura, obesity, time from symptoms onset to diagnosis more than 14 days, and decreased C3 all increased the risk of renal involvement in HSP. The forward stepwise logistic regression analysis indicated obesity (odds ratio (OR) 4.43, 95 % confidence interval (CI) 1.896 to 10.358), age more than 7 years at onset (OR 2.81, 95 % CI 1.142 to 6.907), and persistent purpura (OR 2.57, 95 % CI 1.119 to 5.909) were independent risk factors for renal involvement. Our results show that obesity can increase the hazard of renal involvement in children with HSP and reconfirm that older age at onset and persistent purpura are the independent risk factors for renal involvement. • There have been some reports that obesity was associated with the development of renal injury. • It is not clear whether obesity can increase the risk of renal involvement in children with HSP. What is New: • The main finding of this study is that obesity can increase the hazard of renal involvement in children with HSP.

  7. The Putative Role of the Non-Gastric H+/K+-ATPase ATP12A (ATP1AL1 as Anti-Apoptotic Ion Transporter: Effect of the H+/K+ ATPase Inhibitor SCH28080 on Butyrate-Stimulated Myelomonocytic HL-60 Cells

    Directory of Open Access Journals (Sweden)

    Martin Jakab

    2014-10-01

    Full Text Available Background/Aims: The ATP12A gene codes for a non-gastric H+/K+ ATPase, which is expressed in a wide variety of tissues. The aim of this study was to test for the molecular and functional expression of the non-gastric H+/K+ ATPase ATP12A/ATP1AL1 in unstimulated and butyrate-stimulated (1 and 10 mM human myelomonocytic HL-60 cells, to unravel its potential role as putative apoptosis-counteracting ion transporter as well as to test for the effect of the H+/K+ ATPase inhibitor SCH28080 in apoptosis. Methods: Real-time reverse-transcription PCR (qRT-PCR was used for amplification and cloning of ATP12A transcripts and to assess transcriptional regulation. BCECF microfluorimetry was used to assess changes of intracellular pH (pHi after acute intracellular acid load (NH4Cl prepulsing. Mean cell volumes (MCV and MCV-recovery after osmotic cell shrinkage (Regulatory Volume Increase, RVI were assessed by Coulter counting. Flow-cytometry was used to measure MCV (Coulter principle, to assess apoptosis (phosphatidylserine exposure to the outer leaflet of the cell membrane, caspase activity, 7AAD staining and differentiation (CD86 expression. Results: We found by RT-PCR, intracellular pH measurements, MCV measurements and flow cytometry that ATP12A is expressed in human myelomonocytic HL-60 cells. Treatment of HL-60 cells with 1 mM butyrate leads to monocyte-directed differentiation whereas higher concentrations (10 mM induce apoptosis as assessed by flow-cytometric determination of CD86 expression, caspase activity, phosphatidylserine exposure on the outer leaflet of the cell membrane and MCV measurements. Transcriptional up-regulation of ATP12A and CD86 is evident in 1 mM butyrate-treated HL-60 cells. The H+/K+ ATPase inhibitor SCH28080 (100 µM diminishes K+-dependent pHi recovery after intracellular acid load and blocks RVI after osmotic cell shrinkage. After seeding, HL-60 cells increase their MCV within the first 24 h in culture, and subsequently

  8. 26 CFR 1.528-4 - Substantiality test.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Substantiality test. 1.528-4 Section 1.528-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED... residence. Units which are used for purposes auxiliary to residential use (such as laundry areas, swimming...

  9. Toward More Substantial Theories of Language Acquisition

    Science.gov (United States)

    Jenson, Cinnamon Ann

    2015-01-01

    Cognitive linguists argue that certain sets of knowledge of language are innate. However, critics have argued that the theoretical concept of "innateness" should be eliminated since it is ambiguous and insubstantial. In response, I aim to strengthen theories of language acquisition and identify ways to make them more substantial. I…

  10. [Cause-of-death statistics and ICD, quo vadis?

    Science.gov (United States)

    Eckert, Olaf; Vogel, Ulrich

    2018-07-01

    The International Statistical Classification of Diseases and Related Health Problems (ICD) is the worldwide binding standard for generating underlying cause-of-death statistics. What are the effects of former revisions of the ICD on underlying cause-of-death statistics and which opportunities and challenges are becoming apparent in a possible transition process from ICD-10 to ICD-11?This article presents the calculation of the exploitation grade of ICD-9 and ICD-10 in the German cause-of-death statistics and quality of documentation. Approximately 67,000 anonymized German death certificates are processed by Iris/MUSE and official German cause-of-death statistics are analyzed.In addition to substantial changes in the exploitation grade in the transition from ICD-9 to ICD-10, regional effects become visible. The rate of so-called "ill-defined" conditions exceeds 10%.Despite substantial improvement of ICD revisions there are long-known deficits in the coroner's inquest, filling death certificates and quality of coding. To make better use of the ICD as a methodological framework for mortality statistics and health reporting in Germany, the following measures are necessary: 1. General use of Iris/MUSE, 2. Establishing multiple underlying cause-of-death statistics, 3. Introduction of an electronic death certificate, 4. Improvement of the medical assessment of cause of death.Within short time the WHO will release the 11th revision of the ICD that will provide additional opportunities for the development of underlying cause-of-death statistics and their use in science, public health and politics. A coordinated effort including participants in the process and users is necessary to meet the related challenges.

  11. Inducible nitric oxide synthase gene polymorphisms are associated with a risk of nephritis in Henoch-Schönlein purpura children.

    Science.gov (United States)

    Jiang, Jue; Duan, Wuqiong; Shang, Xu; Wang, Hua; Gao, Ya; Tian, Peijun; Zhou, Qi

    2017-08-01

    Henoch-Schönlein purpura (HSP) is the most common form of systemic small-vessel vasculitis in children, and HSP nephritis (HSPN) is a major complication of HSP and is the primary cause of morbidity and mortality. Previous studies have suggested that inducible nitric oxide synthase (iNOS) may play an important role in the pathogenesis of HSP. In this study, we performed a detailed analysis to investigate the potential association between iNOS polymorphisms and the risk of HSP and the tendency for children with HSP to develop HSPN in a Chinese Han population. A promoter pentanucleotide repeat (CCTTT)n and 10 functional single-nucleotide polymorphisms (SNPs) from 532 healthy controls and 513 children with HSP were genotyped using the MassARRAY system and GeneScan. The results suggested that the allelic and genotypic frequencies of the rs3729508 polymorphism were nominally associated with susceptibility to HSP. In addition, there was a significant difference in the allelic distribution of the (CCTTT)12 repeats and rs2297518 between the HSP children with and without nephritis; the HSP children with nephritis exhibited a significantly higher frequency of the (CCTTT)12 repeats and A allele of rs2297518 than the HSP children without nephritis (P FDR  = 0.033, OR = 1.624, 95% CI = 1.177-2.241 and P FDR  = 0.030, OR = 1.660, 95% CI = 1.187-2.321, respectively). Our results support that iNOS polymorphisms are associated with the risk of HSP and may strongly contribute to the genetic basis of individual differences in the progression to nephritis among children with HSP in the Chinese Han population. What is Known: • The etiology of HSP is unknown, but the genetic factors may play an important role in the pathogenesis of HSP. • iNOS could contribute to the development and clinical manifestations of HSP, and this has not been studied extensively so far. What is New: • Our results support that iNOS polymorphisms not only are associated with HSP risk but also

  12. New family of lanthanide-based inorganic-organic hybrid frameworks: Ln2(OH)4[O3S(CH2)nSO3]·2H2O (Ln = La, Ce, Pr, Nd, Sm; n = 3, 4) and their derivatives.

    Science.gov (United States)

    Liang, Jianbo; Ma, Renzhi; Ebina, Yasuo; Geng, Fengxia; Sasaki, Takayoshi

    2013-02-18

    We report the synthesis and structure characterization of a new family of lanthanide-based inorganic-organic hybrid frameworks, Ln(2)(OH)(4)[O(3)S(CH(2))(n)SO(3)]·2H(2)O (Ln = La, Ce, Pr, Nd, Sm; n = 3, 4), and their oxide derivatives. Highly crystallized samples were synthesized by homogeneous precipitation of Ln(3+) ions from a solution containing α,ω-organodisulfonate salts promoted by slow hydrolysis of hexamethylenetetramine. The crystal structure solved from powder X-ray diffraction data revealed that this material comprises two-dimensional cationic lanthanide hydroxide {[Ln(OH)(2)(H(2)O)](+)}(∞) layers, which are cross-linked by α,ω-organodisulfonate ligands into a three-dimensional pillared framework. This hybrid framework can be regarded as a derivative of UCl(3)-type Ln(OH)(3) involving penetration of organic chains into two {LnO(9)} polyhedra. Substitutional modification of the lanthanide coordination promotes a 2D arrangement of the {LnO(9)} polyhedra. A new hybrid oxide, Ln(2)O(2)[O(3)S(CH(2))(n)SO(3)], which is supposed to consist of alternating {[Ln(2)O(2)](2+)}(∞) layers and α,ω-organodisulfonate ligands, can be derived from the hydroxide form upon dehydration/dehydroxylation. These hybrid frameworks provide new opportunities to engineer the interlayer chemistry of layered structures and achieve advanced functionalities coupled with the advantages of lanthanide elements.

  13. One Minute of Marijuana Secondhand Smoke Exposure Substantially Impairs Vascular Endothelial Function.

    Science.gov (United States)

    Wang, Xiaoyin; Derakhshandeh, Ronak; Liu, Jiangtao; Narayan, Shilpa; Nabavizadeh, Pooneh; Le, Stephenie; Danforth, Olivia M; Pinnamaneni, Kranthi; Rodriguez, Hilda J; Luu, Emmy; Sievers, Richard E; Schick, Suzaynn F; Glantz, Stanton A; Springer, Matthew L

    2016-07-27

    Despite public awareness that tobacco secondhand smoke (SHS) is harmful, many people still assume that marijuana SHS is benign. Debates about whether smoke-free laws should include marijuana are becoming increasingly widespread as marijuana is legalized and the cannabis industry grows. Lack of evidence for marijuana SHS causing acute cardiovascular harm is frequently mistaken for evidence that it is harmless, despite chemical and physical similarity between marijuana and tobacco smoke. We investigated whether brief exposure to marijuana SHS causes acute vascular endothelial dysfunction. We measured endothelial function as femoral artery flow-mediated dilation (FMD) in rats before and after exposure to marijuana SHS at levels similar to real-world tobacco SHS conditions. One minute of exposure to marijuana SHS impaired FMD to a comparable extent as impairment from equal concentrations of tobacco SHS, but recovery was considerably slower for marijuana. Exposure to marijuana SHS directly caused cannabinoid-independent vasodilation that subsided within 25 minutes, whereas FMD remained impaired for at least 90 minutes. Impairment occurred even when marijuana lacked cannabinoids and rolling paper was omitted. Endothelium-independent vasodilation by nitroglycerin administration was not impaired. FMD was not impaired by exposure to chamber air. One minute of exposure to marijuana SHS substantially impairs endothelial function in rats for at least 90 minutes, considerably longer than comparable impairment by tobacco SHS. Impairment of FMD does not require cannabinoids, nicotine, or rolling paper smoke. Our findings in rats suggest that SHS can exert similar adverse cardiovascular effects regardless of whether it is from tobacco or marijuana. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  14. Um estudo observacional do filme Denise está Chamando à luz da teoria de ação de Chris Argyris e Donald Schön Study of the motion picture "Denise Calls Up" focusing on the action theory by Chris Argyris and Donald Schön

    Directory of Open Access Journals (Sweden)

    Nildes R. Pitombo Leite

    2007-01-01

    Full Text Available Este trabalho apresenta uma análise do mundo comportamental retratado no filme Denise está Chamando (Denise Calls Up, de Hal Salwen (1995, cujas características (omissão, distanciamento, manipulação subreptícia, mentiras piedosas, controle e proteção unilaterais são típicas do Oposto ao Modelo I e delicadas para serem identificadas, analisadas e discutidas facilmente nas interações humanas. Esse modelo é oriundo da Teoria de Ação proposta por Chris Argyris e Donald Schön (1977, 1996, aqui utilizados como base de argumentação. Buscou-se, neste trabalho, responder à pergunta de como pesquisadores e consultores podem tornar conhecidos modelos mentais e seus modos de ação. Apresentou-se, ainda, uma perspectiva de análise fílmica, com vistas a contribuir para o incremento de um trabalho científico no Brasil que possa auxiliar grupos e organizações na análise de suas ações. O estudo caracteriza-se como qualitativo, observacional, com base em observação indireta e não-participante. Escolheu-se o método da análise de discurso, baseado em cenas elucidativas da proposição teórica estudada. A fundamentação teórica tentou contextualizar, de modo sucinto, os elementos da Teoria de Ação, identificando, com base no filme, o mundo comportamental que permeia as relações humanas.Behavioral dynamics portrayed in the motion picture, "Denise Calls Up" by Hal Salwen (1955, were analyzed in relation to omission, indifference, surreptitious manipulation, merciful lies and unilateral control and protection. These attitudes are typical of the Opposite of Model I by Chris Argyris and Donald Schön (1995 and are difficult to identify, analyze and discuss in human interactions. Arguments were based on the Model, which was part of their Theory of Action (1977, 1996, and questioned how researchers and consultants could make mental models and modi operandi better known to others. An analysis of the film was also presented thereby

  15. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to foods with reduced lactose content and decreasing gastro-intestinal discomfort caused by lactose intake in lactose intolerant individuals (ID 646, 1224, 1238, 1339

    DEFF Research Database (Denmark)

    Tetens, Inge

    claims in relation to foods with reduced lactose content and decreasing gastro-intestinal discomfort caused by lactose intake in lactose intolerant individuals. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims...... and references that EFSA has received from Member States or directly from stakeholders. The food constituent that is the subject of the health claim is lactose, which should be “decreased” or “reduced” in foods in order to obtain the claimed effect. The Panel considers that lactose is sufficiently characterised....... The claimed effects are “lactose intolerance”, “decrease lactose malabsorption symptoms” and “lactose digestion”. The target population is assumed to be lactose intolerant individuals. The Panel assumes that the claimed effects refer to decreasing gastro-intestinal discomfort caused by lactose intake...

  16. Human-caused Indo-Pacific warm pool expansion.

    Science.gov (United States)

    Weller, Evan; Min, Seung-Ki; Cai, Wenju; Zwiers, Francis W; Kim, Yeon-Hee; Lee, Donghyun

    2016-07-01

    The Indo-Pacific warm pool (IPWP) has warmed and grown substantially during the past century. The IPWP is Earth's largest region of warm sea surface temperatures (SSTs), has the highest rainfall, and is fundamental to global atmospheric circulation and hydrological cycle. The region has also experienced the world's highest rates of sea-level rise in recent decades, indicating large increases in ocean heat content and leading to substantial impacts on small island states in the region. Previous studies have considered mechanisms for the basin-scale ocean warming, but not the causes of the observed IPWP expansion, where expansion in the Indian Ocean has far exceeded that in the Pacific Ocean. We identify human and natural contributions to the observed IPWP changes since the 1950s by comparing observations with climate model simulations using an optimal fingerprinting technique. Greenhouse gas forcing is found to be the dominant cause of the observed increases in IPWP intensity and size, whereas natural fluctuations associated with the Pacific Decadal Oscillation have played a smaller yet significant role. Further, we show that the shape and impact of human-induced IPWP growth could be asymmetric between the Indian and Pacific basins, the causes of which remain uncertain. Human-induced changes in the IPWP have important implications for understanding and projecting related changes in monsoonal rainfall, and frequency or intensity of tropical storms, which have profound socioeconomic consequences.

  17. 76 FR 63846 - Substantially Underserved Trust Areas (SUTA)

    Science.gov (United States)

    2011-10-14

    ... Cost Rural Communities; 10.861, Public Television Station Digital Transition Grant Program; 10.862... rule do not impose substantial unreimbursed direct compliance costs on Indian tribal, Alaska native, or native Hawaiian governments and sovereign institutions or have tribal implications that preempt tribal...

  18. SUBSTANTIATION OF SOLUTIONS PERTAINING TO COMPLEX PRODUCTION RECONSTRUCTION

    Directory of Open Access Journals (Sweden)

    V. Y. Gurinovich

    2011-01-01

    Full Text Available While taking an example of reconstruction and modernization of OJSC «Construction and Mounting Trust No.16, Novopolotsk» the paper substantiates solutions for complex production reconstruction. The production reconstruction is divided in three start-up facilities ensuring continuous finished-product output.

  19. Substantiation of Optimum Stoker Number in Potassium Production by Game Method

    Directory of Open Access Journals (Sweden)

    B. A. Bogatov

    2005-01-01

    Full Text Available Dump formation process of hard halite waste in potassium production has been analyzed in the paper. The paper shows high cost of a salt dump formation and an actuality to substantiate number of ОШ-1900-110/150 stokers that are operating simultaneously. A game theory method has been used to substantiate a solution of the problem.

  20. [{sup 11}C]A-69024: A potent and selective non-benzazepine radiotracer for in vivo studies of dopamine D1 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Kassiou, Michael; Scheffel, Ursula; Ravert, Hayden T; Mathews, William B; Musachio, John L; Lambrecht, Richard M; Dannals, Robert F

    1995-02-01

    [{sup 11}C]A-69024, ({+-})-1-(2-bromo-4,5-dimethoxybenzyl)-7-hydroxy-6-methoxy-2-[{sup 11}C]methyl-1,2= ,3,4-tetrahydroisoquinoline, is a specific and selective dopamine D1 radiotracer. The in vivo biodistribution of this novel radioligand in mice showed a high uptake in the striatum (6.7% ID/g) at 5 min, followed by clearance with a half-life of 16.1 min. As a measure of specificity, the striatal/cerebellar ratio reached a maximum of 7.4 at 30 min post-injection. Radioactivity in the striatum was reduced to the level of the cerebellum by pre-administration of the D1 antagonist SCH 23390 (1 mg/kg). Pretreatment of mice with spiperone (D2), 7-hydroxydipropylaminotetralin (7-OH-DPAT) (D3), clozapine (D4), ketanserin (5-HT2/5-HT2C), mazindol (monoamine reuptake), prazosin ({alpha}{sub 1}), and haloperidol (D2/{sigma}) had no inhibitory effect on [{sup 11}C]A-69024 uptake in the striatum. The dextrotatory enantiomer of the dopamine antagonist butaclamol inhibited striatal uptake, while the less active isomer (-)-butaclamol did not. [{sup 11}C]A-69024 binding was inhibited by unlabeled A-69024 in a dose dependent manner (ED{sub 50} = 0.3 mg/kg) in the striatum while no change occurred in the cerebellum. [{sup 11}C]A-69024 warrants further investigation as a PET ligand for examination of central dopamine D1 receptors in humans.

  1. Systemic blockade of dopamine D2-like receptors increases high-voltage spindles in the globus pallidus and motor cortex of freely moving rats.

    Directory of Open Access Journals (Sweden)

    Chen Yang

    Full Text Available High-voltage spindles (HVSs have been reported to appear spontaneously and widely in the cortical-basal ganglia networks of rats. Our previous study showed that dopamine depletion can significantly increase the power and coherence of HVSs in the globus pallidus (GP and motor cortex of freely moving rats. However, it is unclear whether dopamine regulates HVS activity by acting on dopamine D₁-like receptors or D₂-like receptors. We employed local-field potential and electrocorticogram methods to simultaneously record the oscillatory activities in the GP and primary motor cortex (M1 in freely moving rats following systemic administration of dopamine receptor antagonists or saline. The results showed that the dopamine D₂-like receptor antagonists, raclopride and haloperidol, significantly increased the number and duration of HVSs, and the relative power associated with HVS activity in the GP and M1 cortex. Coherence values for HVS activity between the GP and M1 cortex area were also significantly increased by dopamine D₂-like receptor antagonists. On the contrary, the selective dopamine D₁-like receptor antagonist, SCH23390, had no significant effect on the number, duration, or relative power of HVSs, or HVS-related coherence between M1 and GP. In conclusion, dopamine D₂-like receptors, but not D₁-like receptors, were involved in HVS regulation. This supports the important role of dopamine D₂-like receptors in the regulation of HVSs. An siRNA knock-down experiment on the striatum confirmed our conclusion.

  2. Frequency-Dependent Modulation of Dopamine Release by Nicotine and Dopamine D1 Receptor Ligands: An In Vitro Fast Cyclic Voltammetry Study in Rat Striatum.

    Science.gov (United States)

    Goutier, W; Lowry, J P; McCreary, A C; O'Connor, J J

    2016-05-01

    Nicotine is a highly addictive drug and exerts this effect partially through the modulation of dopamine release and increasing extracellular dopamine in regions such as the brain reward systems. Nicotine acts in these regions on nicotinic acetylcholine receptors. The effect of nicotine on the frequency dependent modulation of dopamine release is well established and the purpose of this study was to investigate whether dopamine D1 receptor (D1R) ligands have an influence on this. Using fast cyclic voltammetry and rat corticostriatal slices, we show that D1R ligands are able to modulate the effect of nicotine on dopamine release. Nicotine (500 nM) induced a decrease in dopamine efflux at low frequency (single pulse or five pulses at 10 Hz) and an increase at high frequency (100 Hz) electrical field stimulation. The D1R agonist SKF-38393, whilst having no effect on dopamine release on its own or on the effect of nicotine upon multiple pulse evoked dopamine release, did significantly prevent and reverse the effect of nicotine on single pulse dopamine release. Interestingly similar results were obtained with the D1R antagonist SCH-23390. In this study we have demonstrated that the modulation of dopamine release by nicotine can be altered by D1R ligands, but only when evoked by single pulse stimulation, and are likely working via cholinergic interneuron driven dopamine release.

  3. [{sup 11}C]NNC 22-0215, a metabolically stable dopamine D{sub 1} radioligand for PET

    Energy Technology Data Exchange (ETDEWEB)

    Foged, Christian; Halldin, Christer; Swahn, Carl-Gunnar; Ginovart, Nathalie; Karlsson, Per; Lundkvist, Camilla; Farde, Lars

    1998-07-01

    NNC 22-0215 has been found to be a metabolically stable dopamine D{sub 1} antagonist with high affinity and selectivity for D{sub 1} receptors in vitro. We prepared [{sup 11}C]NNC 22-0215 with a specific radioactivity of about 50 GBq/{mu}mol at time of administration. In PET experiments with [{sup 11}C]NNC 22-0215 there was a rapid uptake of radioactivity in the cynomolgus monkey brain (1.8% of total radioactivity injected). Radioactivity accumulated most markedly in the striatum and the neocortex. The striatum to cerebellum ratio was about 4, with specific binding that remained at a plateau level from 50 min to 100 min after injection. Binding in the striatum and neocortex was markedly displaced by SCH 23390, whereas binding in the cerebellum was not reduced. Metabolite studies showed that about 80% of the radioactivity in the monkey plasma represented unchanged radioligand 30 min after injection. The rate of metabolism in monkey plasma in vivo was also determined for a series of structurally related {sup 11}C-labelled benzazepines, previously used as dopamine D{sub 1} receptor ligands for PET. Results indicate a significantly slower rate of metabolism for [{sup 11}C]NNC 22-0215 than for any of the previously labelled benzazepines. Thus [{sup 11}C]NNC 22-0215 has potential for imaging of selective binding to the dopamine D{sub 1} receptors in the human brain with high count rates at time of equilibrium.

  4. Antidepressant-like effect of Hoodia gordonii in a forced swimming test in mice: evidence for involvement of the monoaminergic system

    Directory of Open Access Journals (Sweden)

    M.C.O. Citó

    2015-01-01

    Full Text Available Hoodia gordonii is a plant species used traditionally in southern Africa to suppress appetite. Recently, it has been associated with a significant increase in blood pressure and pulse rate in women, suggesting sympathomimetic activity. The present study investigated the possible antidepressant-like effects of acute and repeated (15 days administration of H. gordonii extract (25 and 50 mg/kg, po to mice exposed to a forced swimming test (FST. Neurochemical analysis of brain monoamines was also carried out to determine the involvement of the monoaminergic system on these effects. Acute administration of H. gordonii decreased the immobility of mice in the FST without accompanying changes in general activity in the open-field test during acute treatment, suggesting an antidepressant-like effect. The anti-immobility effect of H. gordonii was prevented by pretreatment of mice with PCPA [an inhibitor of serotonin (5-HT synthesis], NAN-190 (a 5-HT1A antagonist, ritanserin (a 5-HT2A/2C antagonist, ondansetron (a 5-HT3A antagonist, prazosin (an α1-adrenoceptor antagonist, SCH23390 (a D1 receptor antagonist, yohimbine (an α2-adrenoceptor antagonist, and sulpiride (a D2 receptor antagonist. A significant increase in 5-HT levels in the striatum was detected after acute administration, while 5-HT, norepinephrine and dopamine were significantly elevated after chronic treatment. Results indicated that H. gordonii possesses antidepressant-like activity in the FST by altering the dopaminergic, serotonergic, and noradrenergic systems.

  5. GABAA receptors, but not dopamine, serotonin or NMDA receptors, are increased in the frontal cortex from schizophrenic subjects

    International Nuclear Information System (INIS)

    Daen, B.; Hussain, T.; Scarr, E.; Tomaskovic, E.; Kitsoulis, S.; Pavey, G.; Hill, C.; Keks, N.; Opeskin, K.; Copolov, D.L.

    1998-01-01

    Full text: Having shown changed 5HT 2A receptor density in the frontal cortex (FC) from schizophrenic subjects (1) we now report on further studies of the molecular neuroanatomy of the FC in schizophrenia. We used in situ radioligand binding and autoradiography to measure the density of [ 3 H]8OH-DPAT (1 nM) binding (5HT 1A receptors) and [ 3 H]GR113808 (2.4nM) binding (5HT 4 receptors) in Brodmann's areas (BA) 8, 9 and 10 from 10 schizophrenic and 10 controls subjects. In addition, [ 3 H]muscimol (100 nM) binding (GABA A receptors), [ 3 H]TCP (20nM) binding (NMDA receptors), [ 3 H]SCH 23390 (3nM) binding (DA D 1 like receptors) and [ 3 H]YM-09151-2 (4nM) binding (DA D 2 -like receptors) was measured in BA 9 from 17 schizophrenic and 17 control subjects. Subjects were matched for age and sex and the post-mortem interval for tissue collection did not differ. There was a significant increase (18%) in the density of GABA A receptors in BA 9 from subjects with schizophrenia (p<0.05) with no change in NMDA, dopamine or serotonin receptors. These data support the hypothesis that there are selective changes in neurotransmitter receptors in the FC of subjects with schizophrenia. It is not yet clear if such changes contribute to the pathology of the illness. Copyright (1998) Australian Neuroscience Society

  6. Tipepidine, a non-narcotic antitussive, exerts an antidepressant-like effect in the forced swimming test in adrenocorticotropic hormone-treated rats.

    Science.gov (United States)

    Kawaura, Kazuaki; Ogata, Yukino; Honda, Sokichi; Soeda, Fumio; Shirasaki, Tetsuya; Takahama, Kazuo

    2016-04-01

    We investigated whether tipepidine exerts an antidepressant-like effect in the forced swimming test in adrenocorticotropic hormone (ACTH)-treated rats, which is known as a treatment-resistant depression model, and we studied the pharmacological mechanisms of the effects of tipepidine. Male Wistar rats (5-7 weeks old) were used in this study. Tipepidine (20 and 40 mg/kg, i.p.) decreased the immobility time in the forced swimming test in ACTH-treated rats. The anti-immobility effect of tipepidine was blocked by a catecholamine-depleting agent, alpha-methyl-p-tyrosine (300 mg/kg, s.c.), but not by a serotonin-depleting agent, p-chlorophenylalanine. The anti-immobility effect of tipepidine was also blocked by a dopamine D1 receptor antagonist, SCH23390 (0.02 mg/kg, s.c.) and an adrenaline α2 receptor antagonist, yohimbine (2 mg/kg, i.p.). In microdialysis technique, tipepidine (40 mg/kg, i.p.) increased the extracellular dopamine level of the nucleus accumbens (NAc) in ACTH-treated rats. These results suggest that tipepidine exerts an antidepressant-like effect in the forced swimming test in ACTH-treated rats, and that the effect of tipepidine is mediated by the stimulation of dopamine D1 receptors and adrenaline α2 receptors. The results also suggest that an increase in the extracellular dopamine level in the NAc may be involved in the antidepressant-like effect of tipepidine in ACTH-treated rats. Copyright © 2016. Published by Elsevier B.V.

  7. Systemic blockade of dopamine D2-like receptors increases high-voltage spindles in the globus pallidus and motor cortex of freely moving rats.

    Science.gov (United States)

    Yang, Chen; Ge, Shun-Nan; Zhang, Jia-Rui; Chen, Lei; Yan, Zhi-Qiang; Heng, Li-Jun; Zhao, Tian-Zhi; Li, Wei-Xin; Jia, Dong; Zhu, Jun-Ling; Gao, Guo-Dong

    2013-01-01

    High-voltage spindles (HVSs) have been reported to appear spontaneously and widely in the cortical-basal ganglia networks of rats. Our previous study showed that dopamine depletion can significantly increase the power and coherence of HVSs in the globus pallidus (GP) and motor cortex of freely moving rats. However, it is unclear whether dopamine regulates HVS activity by acting on dopamine D₁-like receptors or D₂-like receptors. We employed local-field potential and electrocorticogram methods to simultaneously record the oscillatory activities in the GP and primary motor cortex (M1) in freely moving rats following systemic administration of dopamine receptor antagonists or saline. The results showed that the dopamine D₂-like receptor antagonists, raclopride and haloperidol, significantly increased the number and duration of HVSs, and the relative power associated with HVS activity in the GP and M1 cortex. Coherence values for HVS activity between the GP and M1 cortex area were also significantly increased by dopamine D₂-like receptor antagonists. On the contrary, the selective dopamine D₁-like receptor antagonist, SCH23390, had no significant effect on the number, duration, or relative power of HVSs, or HVS-related coherence between M1 and GP. In conclusion, dopamine D₂-like receptors, but not D₁-like receptors, were involved in HVS regulation. This supports the important role of dopamine D₂-like receptors in the regulation of HVSs. An siRNA knock-down experiment on the striatum confirmed our conclusion.

  8. Synthesis of Au38(SCH2CH2Ph)24, Au36(SPh-tBu)24, and Au30(S-tBu)18 Nanomolecules from a Common Precursor Mixture.

    Science.gov (United States)

    Rambukwella, Milan; Dass, Amala

    2017-10-17

    Phenylethanethiol protected nanomolecules such as Au 25 , Au 38 , and Au 144 are widely studied by a broad range of scientists in the community, owing primarily to the availability of simple synthetic protocols. However, synthetic methods are not available for other ligands, such as aromatic thiol and bulky ligands, impeding progress. Here we report the facile synthesis of three distinct nanomolecules, Au 38 (SCH 2 CH 2 Ph) 24 , Au 36 (SPh-tBu) 24 , and Au 30 (S-tBu) 18 , exclusively, starting from a common Au n (glutathione) m (where n and m are number of gold atoms and glutathiolate ligands) starting material upon reaction with HSCH 2 CH 2 Ph, HSPh-tBu, and HStBu, respectively. The systematic synthetic approach involves two steps: (i) synthesis of kinetically controlled Au n (glutathione) m crude nanocluster mixture with 1:4 gold to thiol molar ratio and (ii) thermochemical treatment of the purified nanocluster mixture with excess thiols to obtain thermodynamically stable nanomolecules. Thermochemical reactions with physicochemically different ligands formed highly monodispersed, exclusively three different core-size nanomolecules, suggesting a ligand induced core-size conversion and structural transformation. The purpose of this work is to make available a facile and simple synthetic method for the preparation of Au 38 (SCH 2 CH 2 Ph) 24 , Au 36 (SPh-tBu) 24 , and Au 30 (S-tBu) 18 , to nonspecialists and the broader scientific community. The central idea of simple synthetic method was demonstrated with other ligand systems such as cyclopentanethiol (HSC 5 H 9 ), cyclohexanethiol(HSC 6 H 11 ), para-methylbenzenethiol(pMBT), 1-pentanethiol(HSC 5 H 11 ), 1-hexanethiol(HSC 6 H 13 ), where Au 36 (SC 5 H 9 ) 24 , Au 36 (SC 6 H 11 ) 24 , Au 36 (pMBT) 24 , Au 38 (SC 5 H 11 ) 24 , and Au 38 (SC 6 H 13 ) 24 were obtained, respectively.

  9. [Severe hypertriglyceridemia--an important cause of pancreatitis].

    Science.gov (United States)

    Graesdal, Asgeir

    2008-05-01

    Moderate hypertriglyceridaemia is a risk factor for cardiovascular disease and serious hypertriglyceridaemia, with triglyceride values above 10 mmol/L, increases the risk of pancreatitis. Gallstones and alcohol abuse are regarded as the two most important causes of acute pancreatitis, but the considerable risk posed by hypertriglyceridaemia has probably been underrated. It is therefore crucial to acquire updated knowledge and awareness of the fact that high levels of triglycerides can cause pancreatitis. This article is based on current literature retrieved though a search on the topic and clinical experience. Serious hypertriglyceridaemia is a relatively rare condition and its usual cause is genetic predisposition combined with obesity, diabetes or alcohol abuse. Certain types of medication, as well as pregnancy, are also well known causes. Current literature suggests that hypertriglyceridaemia is the cause of pancreatitis in 1-38% of the cases--a substantial variation. The condition is often accompanied by low amylase values and may therefore be underrated as a cause. Our case reports illustrate that the etiology is complex. Plasmapheresis or LDL-apheresis may be indicated when conservative treatment proves insufficient.

  10. 32 CFR 48.302 - Substantiating evidence regarding dependency and age of dependents.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Substantiating evidence regarding dependency and age of dependents. 48.302 Section 48.302 National Defense Department of Defense OFFICE OF THE... Designation of Beneficiaries § 48.302 Substantiating evidence regarding dependency and age of dependents. At...

  11. Patients' substantialization of disease, the hybrid symptom and metaphysical care.

    Science.gov (United States)

    Pârvan, Alexandra

    2015-06-01

    In the context of current scholarship concerned with facilitating integration between the biomedical and the patient-centred models of care, the article suggests that disease brings about an ontological disruption in patients, which is not directly addressed in either model, and may interfere with treatment and therapy outcomes if not met with a type of care termed here as 'metaphysical'. The receipt of diagnosis and medical care can give patients the sense that they are ontologically diminished, or less of a human, and along with physicians' approaches to and discourses about disease, may prompt them to seek ontological restoration or security in the same way as psychologically traumatized patients sometimes do: by treating the disease and/or the experience of harm associated with it as a thing that exists per se. I call this 'substantialization' of disease (or harm) and draw on Augustine's theory of non-substantial deficiencies (physiological and moral) and on Plato's and Plotinus's different takes on such defects in order to discuss what substantialization can do for patients. Based on literature that examines patients' ways of talking about and living with their disease, I speculate that substantialization can generate a 'hybrid symptom', consisting in patterns of exercising agency which may predispose to non-adherence. Ways in which physicians could provide metaphysical care are proposed, along with an understanding of chronic patients as hybrid ontological and agentic units, which draws on theories of enactive cognition. I opine that metaphysical care may facilitate integration between the depersonalized and personalized models of care. © 2014 John Wiley & Sons, Ltd.

  12. Differential Action between Schisandrin A and Schisandrin B in Eliciting an Anti-Inflammatory Action: The Depletion of Reduced Glutathione and the Induction of an Antioxidant Response.

    Directory of Open Access Journals (Sweden)

    Pou Kuan Leong

    Full Text Available Schisandrin A (Sch A and schisandrin B (Sch B are active components of Schisandrae Fructus. We compared the biochemical mechanism underlying the anti-inflammatory action of Sch A and Sch B, using cultured lipopolysaccharide (LPS-stimulated RAW264.7 macrophages and concanavalin (ConA-stimulated mouse splenocytes. Pre-incubation with Sch A or Sch B produced an anti-inflammatory action in LPS-stimulated RAW264.7 cells, as evidenced by the inhibition of the pro-inflammatory c-Jun N-terminal kinases/p38 kinase/nuclear factor-κB signaling pathway as well as the suppression of various pro-inflammatory cytokines and effectors, with the extent of inhibition by Sch A being more pronounced. The greater activity of Sch A in anti-inflammatory response was associated with a greater decrease in cellular reduced glutathione (GSH level and a greater increase in glutathione S-transferase activity than corresponding changes produced by Sch B. However, upon incubation, only Sch B resulted in the activation of the nuclear factor (erythroid-derived 2-like factor 2 and the induction of a significant increase in the expression of thioredoxin (TRX in RAW264.7 cells. The Sch B-induced increase in TRX expression was associated with the suppression of pro-inflammatory cytokines and effectors in LPS-stimulated macrophages. Studies in a mouse model of inflammation (carrageenan-induced paw edema indicated that while long-term treatment with either Sch A or Sch B suppressed the extent of paw edema, only acute treatment with Sch A produced a significant degree of inhibition on the inflammatory response. Although only Sch A decreased the cellular GSH level and suppressed the release of pro-inflammatory cytokines and cell proliferation in ConA-simulated splenocytes in vitro, both Sch A and Sch B treatments, while not altering cellular GSH levels, suppressed ConA-stimulated splenocyte proliferation ex vivo. These results suggest that Sch A and Sch B may act differentially on

  13. Age of onset as a risk factor of renal involvement in Henoch-Schönlein purpura

    Science.gov (United States)

    Ledika, Masayu Amanda; Sapartini, Gartika; Setiabudiawan, Budi

    2014-01-01

    Background Henoch-Schönlein purpura (HSP) is the most common vasculitis in children, characterized by triad of symptoms; palpable purpura without thrombocytopenia, abdominal pain, and arthritis. Renal involvement often occur in children with HSP. No data on the renal involvement of children with HSP in Indonesia, especially West Java. Objective To evaluate renal involvement in children with HSP. Methods Retrospective study was conducted in children with HSP in Department of Child Health, Hasan Sadikin Hospital, from 2006 to 2011. Characteristics and clinical manifestations was reviewed from medical record. HSP was diagnosed by American College of Rheumatology 1990 criteria or European League Against Rheumatism/Pediatric Rheumatology International Trials Organization/Pediatric Rheumatology European Society 2008. Results There were 128 patients, consisting of 82 male (64.9%) and 46 female (35.1%) with ratio 1.8:1. Mean age was 7.9 ± 2.9 years old which range from 6 month to 15 years. Peak morbidity was between 5-10 years old. Prevalence of HSP in Hasan Sadikin Hospital tend to raise from 2.7/100,000 in 2008 to 5.2/100,000 in 2010. In most patients (71%) purpura was the first symptom. Seventy-one patients (44.5%) had arthritis and 89 patients (69.5%) had abdominal pain, while renal involvement was in 28 patients (21.8%). Gastrointestinal manifestations tend to manifest in patients less than 5 years old (p = 0.267), while renal involvement tend to manifest in age group 11-15 years old (p = 0.015) with odds ratio 3.1 (95% confidence interval, 1.2-8.1). Conclusion Renal involvement in children with HSP is more common in age group 11 to 15 years old. PMID:24527410

  14. Child protection decisions to substantiate hospital child protection teams' reports of suspected maltreatment.

    Science.gov (United States)

    Jedwab, Merav; Benbenishty, Rami; Chen, Wendy; Glasser, Saralee; Siegal, Gil; Lerner-Geva, Liat

    2015-02-01

    The present study focuses on the way child protection officers (CPOs) in Israel assess suspected abuse and neglect (SCAN) reports made by hospital child protection teams (CPTs), to determine whether the alleged maltreatment is substantiated. The study was conducted in six medical centers and included 358 reports investigated by CPOs for SCAN. A structured questionnaire was completed by hospital CPTs to capture all relevant information on each child referred to the CPTs. Structured phone interviews were conducted with each of the CPOs who received a CPT report. Bivariate associations and multivariate logistic regressions were conducted to estimate the substantiation rate of cases reported by CPTs and the types of maltreatment substantiated, as well as to identify case characteristics of the child and the family that were associated with the CPOs' substantiation decision. CPO follow-up investigations revealed a substantiation rate of 53.5%. The maltreatment type most commonly substantiated was neglect. The case characteristics associated with substantiation included socio-demographic background, parents' health and functioning, previous contact with social services, characteristics of the hospital referral, medical findings and an assessment of the parents' behaviors. The findings of the study highlighted the importance of cooperation between the health and welfare services and the policy makers. This cooperation is essential for identifying early signs of maltreatment. Enhanced cooperation and effective information transfer between various professionals would help prevent or at least reduce the recurrence of maltreatment and would ensure that the children and their families are treated appropriately. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Sex differences in risk factors for subclinical hypothyroidism

    Directory of Open Access Journals (Sweden)

    Jeonghoon Ha

    2018-04-01

    Full Text Available Objective: To investigate the prevalence of subclinical hypothyroidism (SCH in Korean adults and identify the risk factors for the occurrence of SCH by sex. Design and methods: This study used data from the Sixth Korea National Health and Nutrition Examination Survey (KNHANES VI, a cross-sectional, nationally representative survey, which comprises a health interview survey, a health examination survey and a nutrition survey. To examine SCH, the reference range of thyroid-stimulating hormone (TSH was defined using both the range provided by the test kit manufacturer (SCH-M and a population-based range (SCH-P. We investigated the prevalence of SCH and its risk factors by sex using both reference ranges. Results: The prevalence of SCH in Koreans according to SCH-M (0.35–5.5 μIU/mL was 5.6%, and 3.3% with SCH-P (0.62–6.68 μIU/mL. For men, smoking significantly reduced the incidence of SCH, positive anti-thyroid peroxidase antibody (TPOAb significantly increased the risk of SCH, and in an adjusted model, the risk of SCH in all quartiles increased as the urine iodine creatinine ratio (UICR quartile increased. For women, positive TPOAb was confirmed as a risk factor for SCH, as was the highest UICR quartile. Furthermore, the odds ratio for SCH in urban vs rural residence was 1.78. Conclusions: The prevalence rates of SCH were similar to those reported in the literature and previously known risk factors were confirmed using both TSH reference ranges. The notable findings from this study are that the increased risk of SCH with increased iodine intake was more marked in men than in women and that residential area may be a risk factor for SCH in women.

  16. 45 CFR 233.90 - Factors specific to AFDC.

    Science.gov (United States)

    2010-10-01

    ... physical or mental injury, sexual abuse or exploitation, or negligent treatment or maltreatment of such...) payments with respect to a pregnant woman with no other children receiving assistance, and additionally, at... pregnancy both for the pregnant woman with no other children as well as for the pregnant woman receiving...

  17. Cumulative stress and substantiated maltreatment: the importance of caregiver vulnerability and adult partner violence.

    Science.gov (United States)

    Wekerle, Christine; Wall, Anne-Marie; Leung, Eman; Trocmé, Nico

    2007-04-01

    Our goal is to assess the effect of caregiver vulnerabilities, singly and in combination, on the substantiation of child abuse (physical, sexual) and neglect, while controlling for relevant background variables. We test the moderator role of adult partner violence in qualifying the relationship between caregiver vulnerabilities and maltreatment substantiation. Secondary analyses of the 1998 Canadian Incidence Study of Reported Child Maltreatment (CIS) are used to predict child protective service investigation substantiation versus non-substantiation from a range of caregiver vulnerability factors. Involvement in partner violence was examined as a moderator in the relation between caregiver vulnerabilities and maltreatment substantiation. The CIS is an epidemiological survey of first-reported cases to child protective services, using a random sample of child welfare agencies across Canada. Child welfare workers completed a research form on the child, primary caregiver, family, perpetrator, severity and type of maltreatment, as well as services and court outcomes. All maltreatment classifications were assigned according to the Canadian legal definition of child abuse and neglect. Hierarchical logistic regression analyses were used, with stepped entry of: (1) demographic factors, socioeconomic disadvantage, and caregiver's own history of maltreatment; (2) caregiver vulnerability factors; (3) involvement in partner violence; (4) the interaction between caregiver vulnerability and partner violence. Caregiver substance abuse was found to be the single most potent kind of caregiver vulnerability in predicting maltreatment substantiation. When the total number of vulnerabilities was used as the predictor, prediction across all types of maltreatment increased, especially for substantiated neglect. Analyses also showed that the presence of partner violence in the home exacerbated the effect of caregiver vulnerability on substantiation. The total number of caregiver

  18. Impact of numerical information on risk knowledge regarding human papillomavirus (HPV vaccination among schoolgirls: a randomised controlled trial [Effekt von Zahlenangaben auf das Risikowissen von Schülerinnen zur Humanen Papillomavirus (HPV-Impfung: eine randomisiert-kontrollierte Studie

    Directory of Open Access Journals (Sweden)

    Steckelberg, Anke

    2013-10-01

    recipients: Mean value of risk knowledge score (0–5 points: 4.6±1.0 vs. 2.6±1.2 (mean difference 2.0 (95% CI 1.6–2.4; (P[german] Einführung: In Deutschland wurde die Implementierung der Humanen Papillomavirus (HPV-Impfung für 12–17-jährige Mädchen von diversen Kampagnen begleitet. Evidenz-basierte Informationen, die Zahlenangaben beinhalten, wurden nicht zur Verfügung gestellt. Stattdessen führten die Standardinformationen zu einer Überschätzung des Krebsrisikos und den Effekten der HPV-Impfung. Das Vertrauen in die Fähigkeit von Kindern mit Risiken umzugehen ist gering, insbesondere wenn es sich um sozial benachteiligte Schüler handelt. Das Ziel dieser Studie ist ein Vergleich der Effekte eines Standard-Flyers mit einem Informationsflyer, der Zahlenangaben beinhaltet, hinsichtlich des Risikowissens über die HPV-Impfung bei Schülerinnen. Methoden: Randomisiert-kontrollierte Kurzzeitstudie. Es wurden alle 108 Schülerinnen aus sieben Schulklassen auf die Teilnahme angesprochen und 105 stimmten zu. Die Teilnehmerinnen waren Berufsfachschülerinnen, die den Abschluss der 10. Klasse anstrebten und zur Zielgruppe für eine HPV-Impfung gehörten. Die Kontrollgruppe wurde gebeten, den Standardflyer des Nationalen Netzwerks Frauen und Gesundheit zu lesen. Die Interventionsgruppe erhielt den gleichen Flyer, der jedoch mit numerischen Informationen zum Krebsrisiko und zu den angenommenen Effekten der HPV-Impfung auf die Krebsprävention ergänzt worden war. Als Basischarakteristika wurden Alter, Impfstatus, Einstellung zur HPV-Impfung und Aspekte bezüglich des Migrationshintergrunds erhoben. Der primäre Endpunkt war Risikowissen. Die Fragebogenerhebungen erfolgten unter experimentellen Bedingungen. Die individuelle Randomisierung, die Teilnehmerinnen und die intention-to-treat Datenanalyse waren verblindet. Die Studie wurde vom Ministerium für Bildung und Kultur des Landes Schleswig-Holstein und der Ethikkommission der Hamburger Ärztekammer genehmigt

  19. Domestic violence, parental substance misuse and the decision to substantiate child maltreatment.

    Science.gov (United States)

    Victor, Bryan G; Grogan-Kaylor, Andrew; Ryan, Joseph P; Perron, Brian E; Gilbert, Terri Ticknor

    2018-05-01

    Families that experience domestic violence and parental substance misuse are disproportionately involved with the child welfare system. Prior research suggests that child protective services (CPS) caseworkers are more likely to substantiate maltreatment allegations when domestic violence and parental substance misuse are identified during the investigation, pointing to one possible mechanism for this disproportionate involvement. While previous studies have relied on nationally representative data sets, the current study used administrative records from a large Midwestern child welfare agency that accounts for state-level variation in child welfare policy and practice. A total of 501,060 substantiation decisions made between 2009 and 2013 were examined to assess the influence of caseworker-perceived domestic violence and parental substance misuse on the decision to substantiate reported maltreatment. Results from multilevel modeling suggest that the identification of domestic violence and parental substance misuse during an investigation significantly increased the probability that an allegation would be substantiated. The implication of these findings for child welfare practice are considered in light of the fact that many child welfare agencies do not consider exposure to domestic violence and parental substance misuse in and of themselves to constitute child maltreatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Engineering Substantially Prolonged Human Lifespans: Biotechnological Enhancement and Ethics

    NARCIS (Netherlands)

    Derkx, P.H.J.M.

    2006-01-01

    Substantial extension of the human lifespan has recently become a subject of lively debate. One reason for this is the completion in 2001 of the Human Genome Project and the experimental avenues for biogerontological research it has opened. Another is recent theoretical progress in biogerontology.

  1. Theoretical study of stability and superconductivity of ScHn (n =4 -8 ) at high pressure

    Science.gov (United States)

    Qian, Shifeng; Sheng, Xiaowei; Yan, Xiaozhen; Chen, Yangmei; Song, Bo

    2017-09-01

    The synthesis of hydrogen sulfides, with the potential of high-temperature superconductivity, was recently proposed at high Tc = 203 K. It motivated us to employ an ab initio approach for the predictions of crystal structures to find the stable scandium hydrides. In addition to the earlier predicted three stoichiometries of ScH, ScH2, and ScH3, we identify three other metallic stoichiometries of ScH4, ScH6, and ScH8, which show superconductivity at significantly higher temperatures. The phases of ScH4 and ScH6, whose stability does not require extremely high pressures (ZPE), are primarily ionic compounds containing exotic quasimolecular H2 arrangements. The present electron-phonon calculations revealed the superconductive potential of ScH4 and ScH6 with estimated Tc of 98 K and 129 K at 200 GPa and 130 GPa, respectively. The superconductivity of ScHn stems from the large electron-phonon coupling associated with the wagging, bending, and intermediate-frequency modes attributed mainly to the hydrogen atoms.

  2. Effect of subclinical hypothyroidism on the skeletal system and improvement with short-term thyroxine therapy.

    Science.gov (United States)

    Gao, Cuixia; Wang, Yu; Li, Tingting; Huang, Jing; Tian, Limin

    2017-10-27

    The purpose of the study was to observe changes in the skeletal system of rats with subclinical hypothyroidism (SCH) and to determine whether L-thyroxine (L-T4) administration suppresses those changes. Sixty male Wistar rats were randomly divided into control, SCH, and SCH+T4 groups. SCH was induced in rats by administration of methimazole (MMI), and rats in the SCH+T4 group were treated with L-T4 after 45 days of MMI administration. The SCH group had higher thyroid-stimulating hormone (TSH) level than the control and SCH+T4 groups. There were no differences in serum thyroid hormone (FT4 and FT3) levels among the three groups. Bone mineral density; serum levels of BALP and TRACP-5b, two bone metabolic markers; and the biomechanical properties of the femurs were lower in the SCH group than in the control group. After L-T4 treatment, serum BALP and TRACP-5b levels and the femur biomechanical properties were higher in the SCH+T4 than the SCH group. Histopathological examination revealed damage to the structure of the femur trabecular bone network in rats with SCH, and L-T4 treatment improved this condition to some extent. These findings demonstrate that L-T4 treatment ameliorates the destructive effects of SCH on the skeletal system in rats.

  3. Illicit operation of industrial plant subject to licensing, or of other installations within the purview of the German Federal Emission Control Act (BImSchG), which have been shut down for protection against hazards (section 327, subsection 2, No. 1 Penal Code (StGB)); Das unerlaubte Betreiben von genehmigungsbeduerftigen Anlagen oder sonstigen Anlagen im Sinne des Bundes-Immissionsschutzgesetzes, deren Betrieb zum Schutz vor Gefahren untersagt worden ist (Paragraph 327 Abs.2 Nr.1 StGB)

    Energy Technology Data Exchange (ETDEWEB)

    Ocker, A.

    1995-12-31

    The 18th act of 28 March 1980 for amendment of the German Criminal Code (StGB) incorporated the provisions governing the criminal offence of illicit operation of installations subject to licensing into the StGB. These provisions have until then been forming part of the BImSchG (Federal Act on Emission Control). The study in hand presents a discussion of section 327, subsection 2, No. 1 StGB, because this provision represents a fundamental type of an administration accessory criminal offence and thus is suitable to be taken as a basis for an analysis of the scope of problems covered by the StGB, but having an effect on and being interlaced with offences governed by other acts and legal provisions. The study addresses inter alia items such as the object of legal protection defined by this section of the StGB, the provisions defining the licensability of a non-licensed installation in operation, and the consequences of defective decisions under administrative law on the applicability of criminal law provisions. The specific aspects of section 327 StGB, which are of a dominantly administrative nature, are discussed, in particular those referring to the definition of the term ``industrial installation`` as defined by the BImSchG. [Deutsch] Durch das 18. Strafrechtsaenderungsgesetz vom 28.3.1980 wurde der Straftatbestand des unerlaubten Betreibens von Anlagen, die einer Genehmigung nach dem Bundesimmissionsschutzgesetz beduerfen, aus dem BImSchG in das Kernstrafrecht ueberfuehrt. Die vorliegende Untersuchung versucht eine eingehendere Auseinandersetzung mit Para. 327 Abs. 2 Nr. 1 StGB, weil diese Vorschrift als ein Grundtypus der verwaltungsakzessorischen Straftatbestaende die Gelegenheiit zur vertieften Diskussion von umfassenderen strafrechtlichen Problemkreisen gibt. Angesprochen sind insoweit vor allem die Frage des geschuetzten Rechtsgutes der Norm, der Behandlung der materiellen Genehmigungsfaehigkeit eines ungenehmigten Anlagenbetriebs sowie der Auswirkungen von

  4. Substantiation of strength of TVSA-ALPHA fuel assembly under dynamic seismic loads

    International Nuclear Information System (INIS)

    Tutnov, A.; Kiselev, A.; Kiselev, A.; Krutko, E.; Kiselev, I.; Samoilov, O.; Kaydalov, V.

    2009-01-01

    A special place in the substantiation of the safe operation of fuel assemblies is the assessment their operating capability under seismic loads, leading to short-term (several seconds or tens of seconds) the dynamic effects on the reactor core. The level of acceleration of various elements of the reactor installation can be higher than 1,5 g (g - acceleration of gravity) and depends on the height of these elements relatively the ground, which movement causes an earthquake. This dynamic load cause significant deformation of the active zones design element, in particular of the fuel assemblies (FA), which could lead to a contact (or impact) interaction between them. The report presents the results of studies of stress-strain state of FA of TVSA-ALPHA type under the influence of seismic loads of the 8th level on Richter scale using standard approach. According to a normative approach the natural frequencies and modes of FA are calculated in the preliminary stage. The obtained results are conservative from the point of view that in the real FA design the most loaded SG in the middle of the fuel assemblies are made in a combined with mixing grid variant, which are joint by a common rim. This increases the overall carrying capacity of SG as compared with the calculation SG model. It is also necessary to bear in mind that the dynamic (impact) loading the basic mechanical properties of the material may have a significant difference from static (standard) values. This refers in particular to the yield limit, the value of which can be several times higher than specified in the calculation

  5. Detection of Dew-Point by substantial Raman Band Frequency Jumps (A new Method)

    DEFF Research Database (Denmark)

    Hansen, Susanne Brunsgaard; Berg, Rolf W.; Stenby, Erling Halfdan

    Detection of Dew-Point by substantial Raman Band Frequency Jumps (A new Method). See poster at http://www.kemi.dtu.dk/~ajo/rolf/jumps.pdf......Detection of Dew-Point by substantial Raman Band Frequency Jumps (A new Method). See poster at http://www.kemi.dtu.dk/~ajo/rolf/jumps.pdf...

  6. D region disturbances caused by electromagnetic pulses from lightning

    Science.gov (United States)

    Rodriguez, Juan V.; Inan, Umran S.; Bell, Timothy F.

    1992-01-01

    Attention is given to a simple formulation of the propagation and absorption in a magnetized collisional plasma of EM pulses from lightning which describes the effect of discharge orientation and radiated electric field on the structure and magnitude of heating and secondary ionization in the D region. Radiation from most lightning discharges can heat substantially, but only the most intense (not less than 20 V/m) are likely to cause ionization enhancements not less than 10 percent of the ambient in a single ionization cycle. This dependence on the radiated electric field is modified by the discharge radiation pattern: a horizontal cloud discharge tends to cause larger heating and ionizaton maxima while a vertical return stroke causes disturbances of a larger horizontal extent.

  7. Electron beam induced deposition of silacyclohexane and dichlorosilacyclohexane: the role of dissociative ionization and dissociative electron attachment in the deposition process

    Directory of Open Access Journals (Sweden)

    Ragesh Kumar T P

    2017-11-01

    Full Text Available We present first experiments on electron beam induced deposition of silacyclohexane (SCH and dichlorosilacyclohexane (DCSCH under a focused high-energy electron beam (FEBID. We compare the deposition dynamics observed when growing pillars of high aspect ratio from these compounds and we compare the proximity effect observed for these compounds. The two precursors show similar behaviour with regards to fragmentation through dissociative ionization in the gas phase under single-collision conditions. However, while DCSCH shows appreciable cross sections with regards to dissociative electron attachment, SCH is inert with respect to this process. We discuss our deposition experiments in context of the efficiency of these different electron-induced fragmentation processes. With regards to the deposition dynamics, we observe a substantially faster growth from DCSCH and a higher saturation diameter when growing pillars with high aspect ratio. However, both compounds show similar behaviour with regards to the proximity effect. With regards to the composition of the deposits, we observe that the C/Si ratio is similar for both compounds and in both cases close to the initial molecular stoichiometry. The oxygen content in the DCSCH deposits is about double that of the SCH deposits. Only marginal chlorine is observed in the deposits of from DCSCH. We discuss these observations in context of potential approaches for Si deposition.

  8. Nuclear industry in a country with a substantial oil reserve

    International Nuclear Information System (INIS)

    Alvarez, R.; Castillo, H.; Costa, D.; Galan, I.; Martinez, M.

    1981-01-01

    The importance of the development of a nuclear industry in a country like Mexico, with a substantial oil reserve is analyzed, taking into account the technical, economical, political, ecological and social aspects of the problem. (author)

  9. Endocrine causes of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Marino, Laura; Jornayvaz, François R

    2015-10-21

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed.

  10. Henoch-Schonlein Purpura

    Science.gov (United States)

    ... Types of Vasculitis / Henoch-Schönlein Purpura Henoch-Schönlein Purpura Fast Facts First Description Who gets Henoch-Schönlein ... to serious kidney involvement. Who gets Henoch-Schönlein Purpura (the “typical” patient)? Usually, HSP affects a child ...

  11. Dopamine D1 receptor-dependent regulation of extracellular citrulline level in the rat nucleus accumbens during conditioned fear response.

    Science.gov (United States)

    Saulskaya, Natalia B; Fofonova, Nellia V; Sudorghina, Polina V; Saveliev, Sergey A

    2008-08-01

    Nucleus accumbens (N.Acc) contains a subclass of nitric oxide (NO)-generating interneurons that are presumably regulated by the dopamine input. Receptor mechanisms underlying dopamine-NO interaction in the N.Acc are poorly understood. In the current study, we used in vivo microdialysis combined with high-performance liquid chromatography to examine participation of dopamine D1 receptors in regulation of extracellular levels of citrulline (an NO co-product) in the medial N.Acc of Sprague-Dawley rats during both pharmacological challenge and a conditioned fear response. The intraaccumbal infusion of the D1 receptor agonist SKF-38393 (100-500 microM) increased dose-dependently the local dialysate citrulline levels. The SKF-38393-induced increase in extracellular citrulline was prevented by intraaccumbal infusions of 500 microM 7-nitroindazole, a neuronal NO synthase inhibitor. In behavioral microdialysis experiment, the accumbal levels of extracellular citrulline markedly increased in rats given a mild footshock paired with tone. The presentation of the tone previously paired with footshock (the conditioned fear response) produced a "conditioned" rise of extracellular citrulline levels in the N.Acc which was attenuated by intraaccumbal infusion of 100 microM SCH-23390, a dopamine D1 receptor antagonist, and prevented by intraaccumbal infusion of 500 microM 7-nitroindazole. The results suggest that in the N.Acc, the dopamine D1 receptors might regulate the neuronal NO synthase activity; this dopamine-dependent mechanism seems to participate in activation of the neuronal NO synthase and probably NO formation in this brain area during the conditioned fear response.

  12. Computational and biological evidences on the serotonergic involvement of SeTACN antidepressant-like effect in mice.

    Directory of Open Access Journals (Sweden)

    Mariana G Fronza

    Full Text Available A series of phenylselanyl-1H-1,2,3-triazole-4-carbonitriles with different substituents were screened for their binding affinity with serotonin transporter (SERT and dopamine transporter (DAT by docking molecular. 5-(4methoxyphenyl-1-(2-(phenylselanylphenyl-1H-1,2,3-triazole-4-carbonitrile (SeTACN exhibited the best conformation with SERT even higher than fluoxetine and serotonin, suggesting a competitive inhibition. SeTACN demonstrated additional affinity to other serotonergic receptors involved in antidepressant effects: 5HT1a, 5HT2a and 5HT3. In another set of experiments, SeTACN led to significant reductions in the immobility time of mice submitted to forced swimming test (FST in the dose range of 0.1- 20mg/kg, suggesting an antidepressant-like effect. The possible mechanism of action was investigated using serotonergic and dopaminergic antagonists. The antidepressant-like effect of SeTACN (0.1mg/kg i.g. was prevented by the pretreatment with WAY100635 (a selective 5HT1a antagonist, ketanserin (a 5HT2a/c antagonist and ondansetron (a selective 5ht3 antagonist, PCPA (an inhibitor of serotonin synthesis but not with SCH23390 (dopaminergic D1 antagonist and sulpiride (D2 antagonist. Sub-effective dose of fluoxetine was able to potentiate the effects of a sub-effective dose of SeTACN in FST. None of the treatments affected locomotor activity in open field test (OFT. These results together, suggest that the SeTACN antidepressant-like effect is mediate, at least in parts, by serotonergic system.

  13. Dopamine receptors play distinct roles in sexual behavior expression of rats with a different sexual motivational tone.

    Science.gov (United States)

    Guadarrama-Bazante, Irma L; Canseco-Alba, Ana; Rodríguez-Manzo, Gabriela

    2014-10-01

    Dopamine (DA) plays a central role in the expression of male sexual behavior. The effects of DA-enhancing drugs on copulation seem to vary depending on the dose of the agonist used, the type of DA receptor activated, and the sexual condition of the animals. The aim of the present study was to carry out a systematic analysis of the effects of dopaminergic agonists on the expression of male sexual behavior by sexually competent rats in different sexual motivational states, that is when sexually active (sexually experienced) and when temporarily inhibited (sexually exhausted). To this end, the same doses of the nonselective DA receptor agonist apomorphine, the selective D2-like DA receptor agonist quinpirole, and the selective D1-like DA receptor agonist SKF38393 were injected intraperitoneally to sexually experienced or sexually exhausted male rats and their sexual behavior was recorded. Low apomorphine doses induced expression of sexual behavior in sexually satiated rats, but only reduced the intromission latency of sexually experienced rats. SKF38393 facilitated the expression of sexual behavior by sexually exhausted rats, but not that of sexually experienced males and quinpirole did not exert an effect in both types of animal. In line with these results, the apomorphine-induced reversal of sexual exhaustion was blocked by the D1-like receptor antagonist SCH23390. The data suggest that DA receptors play distinct roles in the expression of sexual behavior by male rats depending on their motivational state and that activation of D1-like receptors promotes the expression of sexual behavior in satiated rats.

  14. Hydroethanolic extract of Carthamus tinctorius induces antidepressant-like effects: modulation by dopaminergic and serotonergic systems in tail suspension test in mice.

    Science.gov (United States)

    Abbasi-Maleki, Saeid; Mousavi, Zahra

    2017-09-01

    Studies indicate that major deficiency in the levels of monoaminergic transmitters is a reason for severe depression. On the other hand, it is shown that Carthamus tinctorius L. (CT) may improve neuropsychological injuries by regulation of the monoamine transporter action. Hence, the present study was undertaken to evaluate the involvement of monoaminergic systems in antidepressant-like effect of CT extract in the tail suspension test (TST) in mice. The mice were intraperitoneally (IP) treated with CT extract (100-400 mg/kg) 1 hr before the TST. To investigate the involvement of monoaminergic systems in antidepressant-like effect, the mice were treated with receptor antagonists 15 min before CT extract treatment (400 mg/kg, IP) and 1 hr before the TST. Findings showed that CT extract (100-400 mg/kg, IP), dose-dependently induced antidepressant-like effect ( P open-field test. Pretreatment of mice with SCH23390, sulpiride, haloperidol, WAY100135, cyproheptadine, ketanserin and p-chlorophenylalanine (PCPA) inhibited the antidepressant-like effect of CT extract (400 mg/kg, IP), but not with prazosin and yohimbine. Co-administration of CT extract (100 mg/kg, IP) with sub-effective doses of fluoxetine (5 mg/kg, IP) or imipramine (5 mg/kg, IP) increased their antidepressant-like response. Our findings firstly showed that components (especially N-Hexadecanoic acid) of CT extract induce antidepressant-like effects by interaction with dopaminergic (D1 and D2) and serotonergic (5HT1A, 5-HT2A receptors) systems. These findings validate the folk use of CT extract for the management of depression.

  15. Dopaminergic modulation of striatal acetylcholine release in rats depleted of dopamine as neonates.

    Science.gov (United States)

    Johnson, B J; Bruno, J P

    1995-02-01

    A repeated sessions, in vivo microdialysis design was used to determine the D1- and D2-like receptor modulation of striatal ACh efflux in intact adult rats and those depleted of DA on postnatal Day 3. Systemic administration of the D1-like agonist SKF 38393 (1.0 or 10.0 mg/kg, or the D2-like antagonist clebopride (1.0 or 10.0 mg/kg) increased ACh efflux in both controls and DA-depleted animals. Systemic administration of the D1-like antagonist SCH 23390 (0.05 or 0.2 mg/kg) or D2-like agonist quinpirole (0.5 or 1.0 mg/kg) decreased ACh efflux in both groups of animals. DA-depleted animals exhibited a larger response than did controls to the lower doses of these drugs. Intrastriatal administration of clebopride (10 microM) increased ACh efflux in DA-depleted animals. Finally, basal and clebopride-stimulated ACh efflux were unaffected by the repeated microdialysis sessions. These data demonstrate that the reciprocal modulation of striatal ACh efflux, seen in controls and in rats depleted of DA as adults, is also present in adults depleted of DA as neonates. Because the roles of D1- and D2-receptors in the expression of motor behavior differ between rats depleted of DA as adults vs as neonates, these data suggest that alterations in the dopaminergic modulation of striatal ACh release do not underlie the sparing from motoric deficits seen in animals depleted of DA as neonates.

  16. Dopamine D2/D3 but not dopamine D1 receptors are involved in the rapid antidepressant-like effects of ketamine in the forced swim test.

    Science.gov (United States)

    Li, Yan; Zhu, Zhuo R; Ou, Bao C; Wang, Ya Q; Tan, Zhou B; Deng, Chang M; Gao, Yi Y; Tang, Ming; So, Ji H; Mu, Yang L; Zhang, Lan Q

    2015-02-15

    Major depressive disorder is one of the most prevalent and life-threatening forms of mental illnesses. The traditional antidepressants often take several weeks, even months, to obtain clinical effects. However, recent clinical studies have shown that ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, exerts rapid antidepressant effects within 2h and are long-lasting. The aim of the present study was to investigate whether dopaminergic system was involved in the rapid antidepressant effects of ketamine. The acute administration of ketamine (20 mg/kg) significantly reduced the immobility time in the forced swim test. MK-801 (0.1 mg/kg), the more selective NMDA antagonist, also exerted rapid antidepressant-like effects. In contrast, fluoxetine (10 mg/kg) did not significantly reduced the immobility time in the forced swim test after 30 min administration. Notably, pretreatment with haloperidol (0.15 mg/kg, a nonselective dopamine D2/D3 antagonist), but not SCH23390 (0.04 and 0.1 mg/kg, a selective dopamine D1 receptor antagonist), significantly prevented the effects of ketamine or MK-801. Moreover, the administration of sub-effective dose of ketamine (10 mg/kg) in combination with pramipexole (0.3 mg/kg, a dopamine D2/D3 receptor agonist) exerted antidepressant-like effects compared with each drug alone. In conclusion, our results indicated that the dopamine D2/D3 receptors, but not D1 receptors, are involved in the rapid antidepressant-like effects of ketamine. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Methamphetamine reduces LTP and increases baseline synaptic transmission in the CA1 region of mouse hippocampus.

    Directory of Open Access Journals (Sweden)

    Jarod Swant

    2010-06-01

    Full Text Available Methamphetamine (METH is an addictive psychostimulant whose societal impact is on the rise. Emerging evidence suggests that psychostimulants alter synaptic plasticity in the brain--which may partly account for their adverse effects. While it is known that METH increases the extracellular concentration of monoamines dopamine, serotonin, and norepinephrine, it is not clear how METH alters glutamatergic transmission. Within this context, the aim of the present study was to investigate the effects of acute and systemic METH on basal synaptic transmission and long-term potentiation (LTP; an activity-induced increase in synaptic efficacy in CA1 sub-field in the hippocampus. Both the acute ex vivo application of METH to hippocampal slices and systemic administration of METH decreased LTP. Interestingly, the acute ex vivo application of METH at a concentration of 30 or 60 microM increased baseline synaptic transmission as well as decreased LTP. Pretreatment with eticlopride (D2-like receptor antagonist did not alter the effects of METH on synaptic transmission or LTP. In contrast, pretreatment with D1/D5 dopamine receptor antagonist SCH23390 or 5-HT1A receptor antagonist NAN-190 abrogated the effect of METH on synaptic transmission. Furthermore, METH did not increase baseline synaptic transmission in D1 dopamine receptor haploinsufficient mice. Our findings suggest that METH affects excitatory synaptic transmission via activation of dopamine and serotonin receptor systems in the hippocampus. This modulation may contribute to synaptic maladaption induced by METH addiction and/or METH-mediated cognitive dysfunction.

  18. Dopamine antagonism decreases willingness to expend physical, but not cognitive, effort: a comparison of two rodent cost/benefit decision-making tasks.

    Science.gov (United States)

    Hosking, Jay G; Floresco, Stan B; Winstanley, Catharine A

    2015-03-01

    Successful decision making often requires weighing a given option's costs against its associated benefits, an ability that appears perturbed in virtually every severe mental illness. Animal models of such cost/benefit decision making overwhelmingly implicate mesolimbic dopamine in our willingness to exert effort for a larger reward. Until recently, however, animal models have invariably manipulated the degree of physical effort, whereas human studies of effort have primarily relied on cognitive costs. Dopamine's relationship to cognitive effort has not been directly examined, nor has the relationship between individuals' willingness to expend mental versus physical effort. It is therefore unclear whether willingness to work hard in one domain corresponds to willingness in the other. Here we utilize a rat cognitive effort task (rCET), wherein animals can choose to allocate greater visuospatial attention for a greater reward, and a previously established physical effort-discounting task (EDT) to examine dopaminergic and noradrenergic contributions to effort. The dopamine antagonists eticlopride and SCH23390 each decreased willingness to exert physical effort on the EDT; these drugs had no effect on willingness to exert mental effort for the rCET. Preference for the high effort option correlated across the two tasks, although this effect was transient. These results suggest that dopamine is only minimally involved in cost/benefit decision making with cognitive effort costs. The constructs of mental and physical effort may therefore comprise overlapping, but distinct, circuitry, and therapeutic interventions that prove efficacious in one effort domain may not be beneficial in another.

  19. Unilateral inactivation of the basolateral amygdala attenuates context-induced renewal of Pavlovian-conditioned alcohol-seeking

    Science.gov (United States)

    Chaudhri, N.; Woods, C. A.; Sahuque, L.L.; Gill, T. M.; Janak, P.H.

    2014-01-01

    Environmental contexts associated with drug use promote craving in humans and drug-seeking in animals. We hypothesized that the basolateral amygdala (BLA) itself, as well as serial connectivity between the basolateral amygdala (BLA) and nucleus accumbens core (NAC core), were required for context-induced renewal of Pavlovian-conditioned alcohol-seeking. Male, Long-Evans rats were trained to discriminate between two conditioned stimuli (CS) - a CS+ that was paired with ethanol (EtOH, 20%, v/v) delivery into a fluid port (0.2 ml/CS+, 3.2 ml/session) and a CS− that was not. Entries into the port during each CS were measured. Next, rats received extinction in a different context where both cues were presented without EtOH. At test, responding to the CS+ and CS− without EtOH was evaluated in the prior training context. Control subjects showed a selective increase in CS+ responding relative to extinction, indicative of renewal. This effect was blocked by pre-test, bilateral inactivation of the BLA using a solution of gamma-amino-butyric-acid receptor agonists (0.1 mM muscimol and 1.0 mM baclofen; M/B; 0.3 µl/side). Renewal was also attenuated following unilateral injections of M/B into the BLA, combined with either M/B, the dopamine D1 receptor antagonist SCH 23390 (0.6 µg/side), or saline infusion in the contralateral NAC core. Hence, unilateral BLA inactivation was sufficient to disrupt renewal, highlighting a critical role for functional activity in the BLA in enabling the reinstatement of alcohol-seeking driven by an alcohol context. PMID:23758059

  20. Association between RAS Gene Polymorphisms (ACE I/D, AGT M235T and Henoch-Schönlein Purpura in a Turkish Population

    Directory of Open Access Journals (Sweden)

    Sinem Nalbantoglu

    2013-01-01

    Full Text Available Henoch-Schönlein purpura (HSP is a small-vessel vasculitis of autoimmune hypersensitivity, and renin-angiotensin system (RAS regulates vascular homeostasis and inflammation with activation of cytokine release. Thus, we aimed to investigate the association between HSP and ACE I/D and AGT M235T polymorphisms. Genotyping was determined by allele specific PCR and PCR-RFLP. We obtained a significant difference in genotype distribution (p = 0.003 and allele frequencies (p 0.05 and allele frequencies (p > 0.05 of the AGT M235T polymorphism. Risk assessment showed significant risk for HSP in the subjects both with the ID + DD genotype (p = 0.019, OR: 2.288, 95% CI: 1.136–4.609 and D allele (OR: D vs. I: 2.0528, 95% CI: 1.3632–3.0912, p = 0.001 while no significant risk was obtained for HSP in the subjects both with the MT + TT genotype (p = 0.312, OR: 1.3905, 95% CI: 0.7326–2.6391 and T allele (OR: T vs. M: 1.065, 95% CI: 0.729–1.557, p = 0.743. Furthermore, when patients were stratified by the presence of certain systemic complications of HSP, no significant association was detected with ACE I/D, and AGT M235T polymorphisms. Our findings suggest that ACE I/D polymorphism is significantly associated with HSP susceptibility.

  1. 20 CFR 416.972 - What we mean by substantial gainful activity.

    Science.gov (United States)

    2010-04-01

    ... INCOME FOR THE AGED, BLIND, AND DISABLED Determining Disability and Blindness Substantial Gainful... consider activities like taking care of yourself, household tasks, hobbies, therapy, school attendance...

  2. Subclinical Hypothyroidism after 131I-Treatment of Graves' Disease: A Risk Factor for Depression?

    Science.gov (United States)

    Yu, Jing; Tian, Ai-Juan; Yuan, Xin; Cheng, Xiao-Xin

    2016-01-01

    Although it is well accepted that there is a close relationship between hypothyroidism and depression, previous studies provided inconsistent or even opposite results in whether subclinical hypothyroidism (SCH) increased the risk of depression. One possible reason is that the etiology of SCH in these studies was not clearly distinguished. We therefore investigated the relationship between SCH resulting from 131I treatment of Graves' disease and depression. The incidence of depression among 95 patients with SCH and 121 euthyroid patients following 131I treatment of Graves' disease was studied. The risk factors of depression were determined with multivariate logistic regression analysis. Thyroid hormone replacement therapy was performed in patients with thyroid-stimulating hormone (TSH) levels exceeding 10 mIU/L. Patients with SCH had significantly higher Hamilton Depression Scale scores, serum TSH and thyroid peroxidase antibody (TPOAb) levels compared with euthyroid patients. Multivariate logistic regression analysis revealed SCH, Graves' eye syndrome and high serum TPO antibody level as risk factors for depression. L-thyroxine treatment is beneficial for SCH patients with serum TSH levels exceeding 10 mIU/L. The results of the present study demonstrated that SCH is prevalent among 131I treated Graves' patients. SCH might increase the risk of developing depression. L-thyroxine replacement therapy helps to resolve depressive disorders in SCH patients with TSH > 10mIU/L. These data provide insight into the relationship between SCH and depression.

  3. EXPERIMENTAL SUBSTANTIATION OF ATTRIBUTIONAL STYLE IN TRAFFIC POLICE OFFICERS’ BEHAVIOR

    Directory of Open Access Journals (Sweden)

    Olga Vladimirovna Merkusheva

    2016-02-01

    Full Text Available The article prepared for the ‘Psychological and Methodological Aspects of Professional Personnel Training at Internal Affairs Bodies of the Russian Federation’ scholar tradition looks at the applied aspect of handling security issues by traffic police officers. It presents the results of empirical study of the employees’ psychological characteristics conducted to substantiate their attributional style, which determines the specific character as well as the qua-lity and reliability of traffic police officers’ performance. Traffic police officers’ attributional style of behavior is researched with the help of attributional cognitive techniques for hazard phenomena detection as well as social perception and attribution technique and is viewed as the most stable entity, which reflects the employee’s personal and professional focus.Goal: to provide empirical substantiation of attributional style in traffic police officers’ behavior as an integral personality characteristic that ensures timely detection of hazard phenomena.

  4. Substantial increase in acceleration potential of pyroelectric crystals

    International Nuclear Information System (INIS)

    Tornow, W.; Lynam, S. M.; Shafroth, S. M.

    2010-01-01

    We report on a substantial increase in the acceleration potential achieved with a LiTaO 3 pyroelectric crystal. With a single 2.5 cm diameter and 2.5 cm long z-cut crystal without electric field-enhancing nanotip we produced positive ion beams with maximal energies between 300 and 310 keV during the cooling phase when the crystal was exposed to 5 mTorr of deuterium gas. These values are about a factor of 2 larger than previously obtained with single pyroelectric crystals.

  5. RELIGIOUS DEMOCRATIZATION IN INDONESIA: STRENGTHENING THE PRO-CEDURAL AND SUBSTANTIAL RELIGIOUS DEMOCRACY

    Directory of Open Access Journals (Sweden)

    Eka Hendry AR.

    2013-06-01

    Full Text Available Inspired by the book of Michael Mann about the dark side of democracy that discusses the paradox between the ideality of democratic values and empirical realities of violence in the name of freedom (democracy, this paper begins with the exposure of the paradox, such as the rise of the violent conflict between groups of people (both ethnic and religious-based and the high prevalence of violence between religious groups in Indonesia. Even worse, a very wrenching violence involves state actors (rulers. This paper tries to understand the roots of the paradox, with a look at how the relationship between state and religion and the religious community trend of Indonesia (especially Muslims. The author argues that the democratization of religion is a solution to the issues. To answer what kind of religious democracy lives in Indonesia, the author analyzes through a religious procedural (or constitutional democratic dimension and religious substantial democratic dimension. The phenomenon of disobedience of law and system and the euphoria of law-making that reflects “intolerance” in several places in Indonesia display the fundamental issue in the religious procedural democracy. Whereas in the context of religious substantial democracy, the prevailing trend of religion that serves as a political and economic vehicle and ignores religion as a substantial aspect of the behavior of the Indonesian society has resulted in the marginalization of religious position and function. Then, the infiltration of the model of political Islam has also led to alienation of the character of the Islamic society of Indonesia, from a democratic pattern to a revival (radical one. In this light, the author needs to present a strategy to encourage religious democracy in Indonesia, structurally through formulating the ideal relation model between state and religion and culturally through a substantial pattern of religion embedded with the character of Indonesian religious

  6. Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Marion, Tracy L., E-mail: tracylmarion@qualyst.com [Curriculum in Toxicology, UNC School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7270 (United States); Perry, Cassandra H., E-mail: cassandraperry@qualyst.com [Qualyst, Inc., Durham, NC 27713 (United States); St Claire, Robert L., E-mail: bobstclaire@qualyst.com [Qualyst, Inc., Durham, NC 27713 (United States); Brouwer, Kim L.R., E-mail: kbrouwer@unc.edu [Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, CB 7569 Kerr Hall, Chapel Hill, NC 27599-7569 (United States)

    2012-05-15

    Sandwich-cultured hepatocytes (SCH) are used commonly to investigate hepatic transport protein-mediated uptake and biliary excretion of substrates. However, little is known about the disposition of endogenous bile acids (BAs) in SCH. In this study, four endogenous conjugated BAs common to rats and humans [taurocholic acid (TCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), and glycochenodeoxycholic acid (GCDCA)], as well as two BA species specific to rodents (α- and β-tauromuricholic acid; α/β TMCA), were profiled in primary rat and human SCH. Using B-CLEAR{sup ®} technology, BAs were measured in cells + bile canaliculi, cells, and medium of SCH by LC-MS/MS. Results indicated that, just as in vivo, taurine-conjugated BA species were predominant in rat SCH, while glycine-conjugated BAs were predominant in human SCH. Total intracellular BAs remained relatively constant over days in culture in rat SCH. Total BAs in control (CTL) cells + bile, cells, and medium were approximately 3.4, 2.9, and 8.3-fold greater in human than in rat. The estimated intracellular concentrations of the measured total BAs were 64.3 ± 5.9 μM in CTL rat and 183 ± 56 μM in CTL human SCH, while medium concentrations of the total BAs measured were 1.16 ± 0.21 μM in CTL rat SCH and 9.61 ± 6.36 μM in CTL human SCH. Treatment of cells for 24 h with 10 μM troglitazone (TRO), an inhibitor of the bile salt export pump (BSEP) and the Na{sup +}-taurocholate cotransporting polypeptide (NTCP), had no significant effect on endogenous BAs measured at the end of the 24-h culture period, potentially due to compensatory mechanisms that maintain BA homeostasis. These data demonstrate that BAs in SCH are similar to in vivo, and that SCH may be a useful in vitro model to study alterations in BA disposition if species differences are taken into account. -- Highlights: ► Bile acids (BAs) were measured in rat and human sandwich-cultured hepatocytes (SCH). ► Cell and medium BA

  7. Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes

    International Nuclear Information System (INIS)

    Marion, Tracy L.; Perry, Cassandra H.; St Claire, Robert L.; Brouwer, Kim L.R.

    2012-01-01

    Sandwich-cultured hepatocytes (SCH) are used commonly to investigate hepatic transport protein-mediated uptake and biliary excretion of substrates. However, little is known about the disposition of endogenous bile acids (BAs) in SCH. In this study, four endogenous conjugated BAs common to rats and humans [taurocholic acid (TCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), and glycochenodeoxycholic acid (GCDCA)], as well as two BA species specific to rodents (α- and β-tauromuricholic acid; α/β TMCA), were profiled in primary rat and human SCH. Using B-CLEAR ® technology, BAs were measured in cells + bile canaliculi, cells, and medium of SCH by LC-MS/MS. Results indicated that, just as in vivo, taurine-conjugated BA species were predominant in rat SCH, while glycine-conjugated BAs were predominant in human SCH. Total intracellular BAs remained relatively constant over days in culture in rat SCH. Total BAs in control (CTL) cells + bile, cells, and medium were approximately 3.4, 2.9, and 8.3-fold greater in human than in rat. The estimated intracellular concentrations of the measured total BAs were 64.3 ± 5.9 μM in CTL rat and 183 ± 56 μM in CTL human SCH, while medium concentrations of the total BAs measured were 1.16 ± 0.21 μM in CTL rat SCH and 9.61 ± 6.36 μM in CTL human SCH. Treatment of cells for 24 h with 10 μM troglitazone (TRO), an inhibitor of the bile salt export pump (BSEP) and the Na + -taurocholate cotransporting polypeptide (NTCP), had no significant effect on endogenous BAs measured at the end of the 24-h culture period, potentially due to compensatory mechanisms that maintain BA homeostasis. These data demonstrate that BAs in SCH are similar to in vivo, and that SCH may be a useful in vitro model to study alterations in BA disposition if species differences are taken into account. -- Highlights: ► Bile acids (BAs) were measured in rat and human sandwich-cultured hepatocytes (SCH). ► Cell and medium BA concentrations

  8. Identifying causes for population decline of the brown hare in agricultural landscapes in Denmark

    DEFF Research Database (Denmark)

    Jensen, Trine-Lee Wincentz

    In recent decades the brown hare (Lepus europaeus) population in Denmark has undergone a substantial decline, but proximate causes are unknown and little is known about actual densities. In this thesis, hare populations are investigated with respect to age composition and reproductive parameters...... proportions in game bags have dropped significantly since the 1950ies. Simple matrix population models with variable juvenile recruitment predict the similar population growth rates as actually observed in the annual bag records. The model substantiates the supposition that declines in the Danish hare...

  9. Progression in Running Intensity or Running Volume and the Development of Specific Injuries in Recreational Runners

    DEFF Research Database (Denmark)

    Ramskov, Daniel; Rasmussen, Sten; Sørensen, Henrik

    2018-01-01

    -training. Participants were randomized to one of two running schedules: Schedule Intensity(Sch-I) or Schedule Volume(Sch-V). Sch-I progressed the amount of high intensity running (≥88% VO2max) each week. Sch-V progressed total weekly running volume. Global positioning system watch or smartphone collected data on running...

  10. The debate on treating subclinical hypothyroidism

    Science.gov (United States)

    Tng, Eng Loon

    2016-01-01

    Subclinical hypothyroidism (SCH) represents a mild or compensated form of primary hypothyroidism. The diagnosis of SCH is controversial, as its symptoms are non-specific and its biochemical diagnosis is arbitrary. The treatment of SCH was examined among non-pregnant adults, pregnant adults and children. In non-pregnant adults, treatment of SCH may prevent its progression to overt hypothyroidism, reduce the occurrence of coronary heart disease, and improve neuropsychiatric and musculoskeletal symptoms associated with hypothyroidism. These benefits are counteracted by cardiovascular, neuropsychiatric and musculoskeletal side effects. SCH is associated with adverse maternal and fetal outcomes that may improve with treatment. Treating SCH in children is safe and may improve growth. Importantly, the evidence in this field is largely from retrospective and prospective studies with design limitations, which precludes a conclusive recommendation for the treatment of SCH. PMID:27779276

  11. The debate on treating subclinical hypothyroidism.

    Science.gov (United States)

    Tng, Eng Loon

    2016-10-01

    Subclinical hypothyroidism (SCH) represents a mild or compensated form of primary hypothyroidism. The diagnosis of SCH is controversial, as its symptoms are non-specific and its biochemical diagnosis is arbitrary. The treatment of SCH was examined among non-pregnant adults, pregnant adults and children. In non-pregnant adults, treatment of SCH may prevent its progression to overt hypothyroidism, reduce the occurrence of coronary heart disease, and improve neuropsychiatric and musculoskeletal symptoms associated with hypothyroidism. These benefits are counteracted by cardiovascular, neuropsychiatric and musculoskeletal side effects. SCH is associated with adverse maternal and fetal outcomes that may improve with treatment. Treating SCH in children is safe and may improve growth. Importantly, the evidence in this field is largely from retrospective and prospective studies with design limitations, which precludes a conclusive recommendation for the treatment of SCH. Copyright: © Singapore Medical Association.

  12. A taxonomic revision of the silphaeformis species-group of the genus Tachinus Gravenhorst (Staphylinidae, Tachyporinae) from China.

    Science.gov (United States)

    Feng, Ting; Schülke, Michael; Li, Li-Zhen

    2013-01-01

    The Chinese species of the silphaeformis group of the genus Tachinus Gravenhorst are revised with fifteen species being treated. Thirteen of them are described as new: T. armatus Feng & Li, sp. n. (Sichuan), T. cavazzutii Feng, Li & Schülke, sp. n. (Sichuan), T. coronatus Feng, Li & Schülke, sp. n. (Ningxia, Qinghai), T. hercules Feng, Li & Schülke, sp. n. (Sichuan), T. hujiayaoi Feng, Li & Schülke, sp. n. (Shaanxi), T. jiuzhaigouensis Feng, Li & Schülke, sp. n. (Sichuan), T. linzhiensis Feng & Li, sp. n. (Tibet), T. maderianus Feng & Li, sp. n. (Sichuan), T. mengdaensis Feng, Li & Schülke, sp. n. (Qinghai), T. oblongoelytratus Feng & Li, sp. n. (Sichuan), T. parahercules Feng, Li & Schülke, sp. n. (Sichuan), T. paralinzhiensis Feng & Li, sp. n. (Tibet), and T. yini Feng, Li & Schülke, sp. n. (Sichuan). The two known species are redescribed based on the holotypes and additional material. Illustrations of the habitus and major diagnostic characters, distributional maps, and identification keys of all species are included.

  13. Allergic contact dermatitis caused by cosmetic products.

    Science.gov (United States)

    González-Muñoz, P; Conde-Salazar, L; Vañó-Galván, S

    2014-11-01

    Contact dermatitis due to cosmetic products is a common dermatologic complaint that considerably affects the patient's quality of life. Diagnosis, treatment, and preventive strategies represent a substantial cost. This condition accounts for 2% to 4% of all visits to the dermatologist, and approximately 60% of cases are allergic in origin. Most cases are caused by skin hygiene and moisturizing products, followed by cosmetic hair and nail products. Fragrances are the most common cause of allergy to cosmetics, followed by preservatives and hair dyes; however, all components, including natural ingredients, should be considered potential sensitizers. We provide relevant information on the most frequent allergens in cosmetic products, namely, fragrances, preservatives, antioxidants, excipients, surfactants, humectants, emulsifiers, natural ingredients, hair dyes, sunscreens, and nail cosmetics. Copyright © 2013 Elsevier España, S.L.U. and AEDV. All rights reserved.

  14. Substantiating the Incurred but not Reported Reserve

    Directory of Open Access Journals (Sweden)

    Georgeta Vintilã

    2009-12-01

    Full Text Available In order to handle past and future liability taken by insurance contracts concluded, any insurance company must constitute and maintain technical reserves. Substantiating technical reserves is done through actuarial methods and its over-evaluation or under-evaluation influence solvency and financial performance of the insurance companies, in the sense of reducing solvency through over-evaluating reserves and, respectively, influencing profit (hence of outstanding tax through under-evaluating reserves. An important reserve for insurance companies is represented by the incurred but not reported reserve, as it allows the estimation of the liability the company may confront in the future, generated by events occurred in the past, which are not currently known in the present but will be reported in the future.

  15. Heating Changes Bio-Schwertmannite Microstructure and Arsenic(III Removal Efficiency

    Directory of Open Access Journals (Sweden)

    Xingxing Qiao

    2017-01-01

    Full Text Available Schwertmannite (Sch is an efficient adsorbent for arsenic(III removal from arsenic(III-contaminated groundwater. In this study, bio-schertmannite was synthesized in the presence of dissolved ferrous ions and Acidithiobacillus ferrooxidans LX5 in a culture media. Bio-synthesized Sch characteristics, such as total organic carbon (TOC, morphology, chemical functional groups, mineral phase, specific surface area, and pore volume were systematically studied after it was dried at 105 °C and then heated at 250–550 °C. Differences in arsenic(III removal efficiency between 105 °C dried-sch and 250–550 °C heated-sch also were investigated. The results showed that total organic carbon content in Sch and Sch weight gradually decreased when temperature increased from 105 °C to 350 °C. Sch partly transformed to another nanocrystalline or amorphous phase above 350 °C. The specific surface area of 250 °C heated-sch was 110.06 m2/g compared to 5.14 m2/g for the 105 °C dried-sch. Total pore volume of 105 °C dried-sch was 0.025 cm3/g with 32.0% mesopore and 68.0% macropore. However, total pore volume of 250 °C heated-mineral was 0.106 cm3/g with 23.6% micropore, 33.0% mesopore, and 43.4% macropore. The arsenic(III removal efficiency from an initial 1 mg/L arsenic(III solution (pH 7.5 was 25.1% when 0.25 g/L of 105 °C dried-sch was used as adsorbent. However, this efficiency increased to 93.0% when using 250 °C heated-sch as adsorbent. Finally, the highest efficiency for arsenic(III removal was obtained with sch-250 °C due to high amounts of sorption sites in agreement with the high specific surface area (SSA obtained for this sample.

  16. 26 CFR 1.6662-4 - Substantial understatement of income tax.

    Science.gov (United States)

    2010-04-01

    ... arrangement does not have as its principal purpose the avoidance or evasion of Federal income tax solely as a... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Substantial understatement of income tax. 1... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Additions to the Tax, Additional Amounts, and Assessable...

  17. Run Clever - No difference in risk of injury when comparing progression in running volume and running intensity in recreational runners

    DEFF Research Database (Denmark)

    Ramskov, Daniel; Rasmussen, Sten; Sørensen, Henrik

    2018-01-01

    Background/aim: The Run Clever trial investigated if there was a difference in injury occurrence across two running schedules, focusing on progression in volume of running intensity (Sch-I) or in total running volume (Sch-V). It was hypothesised that 15% more runners with a focus on progression...... in volume of running intensity would sustain an injury compared with runners with a focus on progression in total running volume. Methods: Healthy recreational runners were included and randomly allocated to Sch-I or Sch-V. In the first eight weeks of the 24-week follow-up, all participants (n=839) followed...... participants received real-time, individualised feedback on running intensity and running volume. The primary outcome was running-related injury (RRI). Results: After preconditioning a total of 80 runners sustained an RRI (Sch-I n=36/Sch-V n=44). The cumulative incidence proportion (CIP) in Sch-V (reference...

  18. 40 CFR Appendix C to Part 112 - Substantial Harm Criteria

    Science.gov (United States)

    2010-07-01

    ... to Part 112 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS OIL POLLUTION PREVENTION Pt. 112, App. C Appendix C to Part 112—Substantial Harm Criteria 1.0Introduction The..., except in the Gulf of Mexico. In the Gulf of Mexico, it means the area shoreward of the lines of...

  19. 20 CFR 416.1080 - Notice of right to hearing on proposed finding of substantial failure.

    Science.gov (United States)

    2010-04-01

    ... agency has substantially failed to meet our standards unless the State submits a written request for a... finding of substantial failure. 416.1080 Section 416.1080 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED Determinations of Disability...

  20. Ancient DNA reveals substantial genetic diversity in the California Condor (Gymnogyps californianus) prior to a population bottleneck

    Science.gov (United States)

    D'Elia, Jesse; Haig, Susan M.; Mullins, Thomas D.; Miller, Mark P.

    2016-01-01

    Critically endangered species that have undergone severe population bottlenecks often have little remaining genetic variation, making it difficult to reconstruct population histories to apply in reintroduction and recovery strategies. By using ancient DNA techniques, it is possible to combine genetic evidence from the historical population with contemporary samples to provide a more complete picture of a species' genetic variation across its historical range and through time. Applying this approach, we examined changes in the mitochondrial DNA (mtDNA) control region (526 base pairs) of the endangered California Condor (Gymnogyps californianus). Results showed a >80% reduction in unique haplotypes over the past 2 centuries. We found no spatial sorting of haplotypes in the historical population; the periphery of the range contained haplotypes that were common throughout the historical range. Direct examination of mtDNA from California Condor museum specimens provided a new window into historical population connectivity and genetic diversity showing: (1) a substantial loss of haplotypes, which is consistent with the hypothesis that condors were relatively abundant in the nineteenth century, but declined rapidly as a result of human-caused mortality; and (2) no evidence of historical population segregation, meaning that the available genetic data offer no cause to avoid releasing condors in unoccupied portions of their historical range.

  1. Analysis of cause-effect relationship of hip dysplasia in pre-school children

    Directory of Open Access Journals (Sweden)

    Anna Rudenko

    2015-12-01

    Full Text Available Purpose: to analyze and scientifically substantiate peculiarities of cause-effect relationship of hip dysplasia in pre-school children. Material and Methods: analysis and systematization of scientific and methodological literature, medical histories, anamneses, interviews and questionings. Results: it is specified that failure to timely identify and eliminate the symptoms of hip dysplasia in pre-school children leads to negative consequences, namely limited amplitude of hip joint movements; lower limp muscle weakness; valgus and varus deformations of lower limp; increasing of L-lordosis; skewness of hip bones; scoliosis; claudication. Conclusions: the modern state of the problem of hip dysplasia in pre-school children is analyzed. The cause-effect relationship is defined, their mutual transition is projected. All cause-effect relationships are in direct proportion and in constant interaction: the cause the forms effect and the effect influences the cause

  2. 49 CFR Schedule G to Subpart B of... - Selected Statistical Data

    Science.gov (United States)

    2010-10-01

    ..., L. 12, col. (b) 26Total passenger revenue Sch. 9002, L. 16, col. (b) 27Passenger-miles per bus mile... PROCEEDINGS Intercity Bus Industry Pt. 1139, Subpt. B, Sch. G Schedule G to Subpart B of Part 1139—Selected.... (b) 2Special bus revenue Sch. 2998, L. 2, col. (b) 3Express revenue Sch. 2998, L. 5, col. (b) 4Total...

  3. Local perceptions of causes of death in rural South Africa: a comparison of perceived and verbal autopsy causes of death.

    Science.gov (United States)

    Hussain-Alkhateeb, Laith; Fottrell, Edward; Petzold, Max; Kahn, Kathleen; Byass, Peter

    2015-01-01

    Understanding how lay people perceive the causes of mortality and their associated risk factors is important for public health. In resource-limited settings, where verbal autopsy (VA) is used as the most expedient method of determining cause of death, it is important to understand how pre-existing concepts of cause of death among VA-informants may influence their VA-responses and the consequential impact on cause of death assessment. This study describes the agreement between VA-derived causes of death and informant-perceived causes and associated influential factors, which also reflects lay health literacy in this setting. Using 20 years of VA data (n=11,228) from the Agincourt Health and Demographic Surveillance System (HDSS) site in rural South Africa, we explored the agreement between the causes of death perceived by the VA-informants and those assigned by the automated Inter-VA tool. Kappa statistics and concordance correlation coefficients were applied to measure agreement at individual and population levels, respectively. Multivariable regression models were used to explore factors associated with recognised lay perceptions of causes of mortality. Agreement between informant-perceived and VA-derived causes of death at the individual level was limited, but varied substantially by cause of death. However, agreement at the population level, comparing cause-specific mortality fractions was higher, with the notable exception of bewitchment as a cause. More recent deaths, those in adults aged 15-49 years, deaths outside the home, and those associated with external causes showed higher concordance with InterVA. Overall, informant perception of causes of death was limited, but depended on informant characteristics and causes of death, and to some extent involved non-biomedical constructs. Understanding discordance between perceived and recognised causes of death is important for public health planning; low community understanding of causes of death may be

  4. Local perceptions of causes of death in rural South Africa: a comparison of perceived and verbal autopsy causes of death

    Science.gov (United States)

    Hussain-Alkhateeb, Laith; Fottrell, Edward; Petzold, Max; Kahn, Kathleen; Byass, Peter

    2015-01-01

    Background Understanding how lay people perceive the causes of mortality and their associated risk factors is important for public health. In resource-limited settings, where verbal autopsy (VA) is used as the most expedient method of determining cause of death, it is important to understand how pre-existing concepts of cause of death among VA-informants may influence their VA-responses and the consequential impact on cause of death assessment. This study describes the agreement between VA-derived causes of death and informant-perceived causes and associated influential factors, which also reflects lay health literacy in this setting. Method Using 20 years of VA data (n=11,228) from the Agincourt Health and Demographic Surveillance System (HDSS) site in rural South Africa, we explored the agreement between the causes of death perceived by the VA-informants and those assigned by the automated Inter-VA tool. Kappa statistics and concordance correlation coefficients were applied to measure agreement at individual and population levels, respectively. Multivariable regression models were used to explore factors associated with recognised lay perceptions of causes of mortality. Results Agreement between informant-perceived and VA-derived causes of death at the individual level was limited, but varied substantially by cause of death. However, agreement at the population level, comparing cause-specific mortality fractions was higher, with the notable exception of bewitchment as a cause. More recent deaths, those in adults aged 15–49 years, deaths outside the home, and those associated with external causes showed higher concordance with InterVA. Conclusion Overall, informant perception of causes of death was limited, but depended on informant characteristics and causes of death, and to some extent involved non-biomedical constructs. Understanding discordance between perceived and recognised causes of death is important for public health planning; low community

  5. TECHNICAL AND ECONOMIC SUBSTANTIATION OF PROJECTS OF THE AFFORDABLE HOUSING CONSTRUCTION

    Directory of Open Access Journals (Sweden)

    KRAVCHUNOVSKA T. S.

    2015-12-01

    Full Text Available Summary. Problem statement. The development of inhabitant locality of Ukraine is characterized by significant differences in levels of socio and economic development. An excessive concentration of population and industry in large cities, inefficient, slow development of most medium and small cities, towns and villages, considerable territorial disproportions of economic development of the country, considerable shortcomings in the territorial organization of society are observed. At the same time the tendency of the total area of increasing of inhabitant locality. The lands are used inefficiently. Among the most common problems of inhabitant locality is the housing problem. When making a decision on the design of affordable housing construction is one of the most important stages in the development of the technique and economic substantiation of the project is determination of the advisability and effectiveness of construction. The substantiation of advisability and effectiveness of affordable housing based on the definition of technical and economic indicators of projects, one of the most important among them is the cost, in its calculation is necessary to take into account the influence of organizational and technological factors, reflecting the features of construction in condition of compacted construction. Purpose. Development of methodical recommendations on substantiation of cost construction of affordable housing in the conditions of compacted construction. Conclusion. To provide a processing and the analysis of data is necessary development of the applied software on the basis of the developed block scheme of justification of cost construction of affordable housing.

  6. Substantiation of the road toll for heavy transport vehicles

    OpenAIRE

    Burmaka, N.; Chernykh, A.

    2010-01-01

    The existing and possible additional sources of developing state and local road funds of Ukraine have been considered. The formula for calculating monthly road toll for heavy transport vehicles has been proposed. This formula includes the payment rate per every kilometer of distance, the vehicle capacity utilization factor and the run with the load. The payment rate per every kilometer of distance for transport vehicles depending on the allowed total weight has been substantiated. The given r...

  7. 20 CFR 404.1680 - Notice of right to hearing on proposed finding of substantial failure.

    Science.gov (United States)

    2010-04-01

    ... agency has substantially failed to meet our standards unless the State submits a written request for a... finding of substantial failure. 404.1680 Section 404.1680 Employees' Benefits SOCIAL SECURITY..., following the mandatory performance support period and the 3-month adjustment period, a State agency again...

  8. Smoking-related general and cause-specific mortality in Estonia.

    Science.gov (United States)

    Kõks, Gea; Fischer, Krista; Kõks, Sulev

    2017-07-19

    Tobacco smoking is known to be the single largest cause of premature death worldwide. The aim of present study was to analyse the effect of smoking on general and cause-specific mortality in the Estonian population. The data from 51,756 adults in the Estonian Genome Center of the University of Tartu was used. Information on dates and causes of death was retrieved from the National Causes of Death Registry. Smoking status, general survival, general mortality and cause-specific mortality were analysed using Kaplan-Meier estimator and Cox proportional hazards models. The study found that smoking reduces median survival in men by 11.4 years and in women by 5.8 years. Tobacco smoking produces a very specific pattern in the cause of deaths, significantly increasing the risks for different cancers and cardiovascular diseases as causes of death for men and women. This study also identified that external causes, such as alcohol intoxication and intentional self-harm, are more prevalent causes of death among smokers than non-smokers. Additionally, smoking cessation was found to reverse the increased risks for premature mortality. Tobacco smoking remains the major cause for losses of life inducing cancers and cardiovascular diseases. In addition to the common diseases, external causes also reduce substantially the years of life. External causes of death indicate that smoking has a long-term influence on the behaviour of smokers, provoking self-destructive behaviour. Our study supports the idea, that tobacco smoking generates complex harm to our health increasing mortality from both somatic and mental disorders.

  9. All-Cause and Cause-Specific Mortality among Users of Basal Insulins NPH, Detemir, and Glargine.

    Directory of Open Access Journals (Sweden)

    Arto Y Strandberg

    Full Text Available Insulin therapy in type 2 diabetes may increase mortality and cancer incidence, but the impact of different types of basal insulins on these endpoints is unclear. Compared to the traditional NPH insulin, the newer, longer-acting insulin analogues detemir and glargine have shown benefits in randomized controlled trials. Whether these advantages translate into lower mortality among users in real life is unknown.To estimate the differences in all-cause and cause-specific mortality rates between new users of basal insulins in a population-based study in Finland.23 751 individuals aged ≥40 with type 2 diabetes, who initiated basal insulin therapy in 2006-2009 were identified from national registers, with comprehensive data for mortality, causes of death, and background variables. Propensity score matching was performed on characteristics. Follow-up time was up to 4 years (median 1.7 years.2078 deaths incurred. With NPH as reference, the adjusted HRs for all-cause mortality were 0.39 (95% CI, 0.30-0.50 for detemir, and 0.55 (95% CI, 0.44-0.69 for glargine. As compared to glargine, the HR was 0.71 (95% CI, 0.54-0.93 among detemir users. Compared to NPH, the mortality risk for both cardiovascular causes as well as cancer were also significantly lower for glargine, and especially for detemir in adjusted analysis. Furthermore, the results were robust in various sensitivity analyses.In real clinical practice, mortality was substantially higher among users of NPH insulin as compared to insulins detemir or glargine. Considering the large number of patients who require insulin therapy, this difference in risk may have major clinical and public health implications. Due to limitations of the observational study design, further investigation using an interventional study design is warranted.

  10. All-Cause and Cause-Specific Mortality among Users of Basal Insulins NPH, Detemir, and Glargine.

    Science.gov (United States)

    Strandberg, Arto Y; Hoti, Fabian J; Strandberg, Timo E; Christopher, Solomon; Haukka, Jari; Korhonen, Pasi

    2016-01-01

    Insulin therapy in type 2 diabetes may increase mortality and cancer incidence, but the impact of different types of basal insulins on these endpoints is unclear. Compared to the traditional NPH insulin, the newer, longer-acting insulin analogues detemir and glargine have shown benefits in randomized controlled trials. Whether these advantages translate into lower mortality among users in real life is unknown. To estimate the differences in all-cause and cause-specific mortality rates between new users of basal insulins in a population-based study in Finland. 23 751 individuals aged ≥40 with type 2 diabetes, who initiated basal insulin therapy in 2006-2009 were identified from national registers, with comprehensive data for mortality, causes of death, and background variables. Propensity score matching was performed on characteristics. Follow-up time was up to 4 years (median 1.7 years). 2078 deaths incurred. With NPH as reference, the adjusted HRs for all-cause mortality were 0.39 (95% CI, 0.30-0.50) for detemir, and 0.55 (95% CI, 0.44-0.69) for glargine. As compared to glargine, the HR was 0.71 (95% CI, 0.54-0.93) among detemir users. Compared to NPH, the mortality risk for both cardiovascular causes as well as cancer were also significantly lower for glargine, and especially for detemir in adjusted analysis. Furthermore, the results were robust in various sensitivity analyses. In real clinical practice, mortality was substantially higher among users of NPH insulin as compared to insulins detemir or glargine. Considering the large number of patients who require insulin therapy, this difference in risk may have major clinical and public health implications. Due to limitations of the observational study design, further investigation using an interventional study design is warranted.

  11. Substantial variation in the interpretation of financial disclosure policies for orthopaedic society meetings.

    Science.gov (United States)

    Jegede, Kolawole; Whang, Peter; Grauer, Jonathan N

    2011-07-06

    were to answer a global question incorrectly. This study clearly demonstrated a discrepancy between what societies intend to identify with disclosure policies and what the orthopaedist interprets is intended. Almost half of those completing the survey did not correctly understand the intention of three or more of the policies, even with expected study intent bias. This study showed that the language used in disclosure policy statements and the lack of a uniform policy may be a cause of substantial discrepancies in potential conflict-of-interest disclosure.

  12. Pulmonary biology of anti-interleukin 5 antibodies

    Directory of Open Access Journals (Sweden)

    RW Egan

    1997-12-01

    Full Text Available Interleukin 5 (IL-5 is a critical cytokine for the maturation of eosinophil precursors to eosinophils in the bone marrow and those eosinophils then accumulate in the lungs during asthma. We have studied anti IL-5 antibodies on allergic responses in mice, guinea pigs and monkeys and are extending this experiment into humans with a humanized antibody. In a monkey model of pulmonary inflammation and airway hyperreactivity, we found that the TRFK-5 antibody blocked both responses for three months following a single dose of 0.3 mg/kg, i.v. This antibody also blocked lung eosinophilia in mice by inhibiting release from the bone marrow. To facilitate multiple dosing and to reduce immunogenicity in humans, we prepared Sch 55700, a humanized antibody against IL-5. Sch 55700 was also active against lung eosinophilia in allergic monkeys and mice and against pulmonary eosinophilia and airway hyperresponsiveness in guinea pigs. Furthermore, as opposed to steroids, Sch 55700 did not cause immunosuppression in guinea pigs. Studies with this antibody in humans will be critical to establishing the therapeutic potential of IL-5 inhibition.

  13. Experience with diagnosis of root causes of human performance problems in Indian nuclear power plants

    International Nuclear Information System (INIS)

    Bhattacharya, A.S.

    1997-01-01

    Low capacity factor, in any NPP, is a result of high occurrence rates of significant events. A substantial portion of such occurrences is caused by inappropriate action due to inadequate human performance. To improve human performance we need first to do its evaluation. This paper describes the essential elements of the first basic step in that context: diagnosis or identification of the fundamental causes of human performance problems in Indian NPPs. (author)

  14. Causes of corruption: Evidence from sub-Saharan Africa

    Directory of Open Access Journals (Sweden)

    Joseph Ato Forson

    2016-11-01

    Full Text Available This study explores the causes of corruption in 22 countries in sub-Saharan Africa from 1996 to 2013. The sources of corruption are grouped into three main thematic areas – historical roots, contemporary causes and institutional causes to make way for subjective and objective measures. The subjective measures allow for assessment of the effectiveness of anticorruption policies. Using pooled OLS, fixed-effect and instrumental-variable approaches, and focusing on the perceived level of corruption as the dependent variable, we find that ethnic diversity, resource abundance and educational attainment are markedly less associated with corruption. In contrast, wage levels of bureaucrats and anticorruption measures based on government effectiveness and regulatory quality breed substantial corruption. Press freedom is found to be variedly associated with corruption. On the basis of these findings, we recommend that the fight against corruption on the continent needs to be reinvented through qualitative and assertive institutional reforms. Anticorruption policy decisions should focus on existing educational systems as a conduit for intensifying awareness of the devastating effect of corruption on sustainable national development.

  15. Weeds Cause Losses in Field Crops through Allelopathy

    Directory of Open Access Journals (Sweden)

    Ali ZOHAIB

    2016-03-01

    Full Text Available A large number of weeds are known to be associated with crops and causing economic losses. Weeds interfere with crops through competition and allelopathy. They produce secondary metabolites known as allelochemicals, which belong to numerous chemical classes such as phenolics, alkaloids, fatty acids, indoles, terpens etc. However, phenolics are the predominant class of allelochemicals. The allelochemicals release from weed plants takes place through leaf leachates, decomposition of plant residues, volatilization and root exudates. Weeds leave huge quantities of their residues in field and affect the associated, as well as succeeding crops, in various cropping systems. Liberation of allelochemicals from weeds affects the germination, stand establishment, growth, yield and physiology of crop plants. They cause substantial reduction in germination and growth of the crop plants by altering various physiological processes such as enzyme activity, protein synthesis, photosynthesis, respiration, cell division and enlargement, which ultimately leads to a significant reduction in crop yield. In crux, allelopathic weeds represent a potential threat for crop plants and cause economic losses.

  16. Subclinical Hypothyroidism Is Independently Associated with Microalbuminuria in a Cohort of Prediabetic Egyptian Adults

    Directory of Open Access Journals (Sweden)

    Mervat M. El-Eshmawy

    2013-12-01

    Full Text Available BackgroundRecent evidence has suggested an association between subclinical hypothyroidism (SCH and microalbuminuria in patients with type 2 diabetes. However, whether SCH is related to microalbuminuria among subjects with prediabetes has not been studied. Thus, we evaluated the association between SCH and microalbuminuria in a cohort of prediabetic Egyptian adults.MethodsA total of 147 prediabetic subjects and 150 healthy controls matched for age and sex were enrolled in this study. Anthropometric measurements, plasma glucose, lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR, thyroid stimulating hormone (TSH, free thyroxine, triiodothyronine levels, and urinary albumin-creatinine ratio (UACR were assessed.ResultsThe prevalence of SCH and microalbuminuria in the prediabetic subjects was higher than that in the healthy controls (16.3% vs. 4%, P<0.001; and 12.9% vs. 5.3%, P=0.02, respectively. Prediabetic subjects with SCH were characterized by significantly higher HOMA-IR, TSH levels, UACR, and prevalence of microalbuminuria than those with euthyroidism. TSH level was associated with total cholesterol (P=0.05, fasting insulin (P=0.01, HOMA-IR (P=0.01, and UACR (P=0.005. UACR was associated with waist circumference (P=0.01, fasting insulin (P=0.05, and HOMA-IR (P=0.02. With multiple logistic regression analysis, SCH was associated with microalbuminuria independent of confounding variables (β=2.59; P=0.01.ConclusionOur findings suggest that prediabetic subjects with SCH demonstrate higher prevalence of microalbuminuria than their non-SCH counterparts. SCH is also independently associated with microalbuminuria in prediabetic subjects. Screening and treatment for SCH may be warranted in those patients.

  17. 75 FR 27504 - Substantial Product Hazard List: Hand-Held Hair Dryers

    Science.gov (United States)

    2010-05-17

    ... immersion during their use. Section 15(a) of the CPSA defines ``substantial product hazard'' to include, a....'' Hand-held hair dryers routinely contain open-coil heating elements that are, in essence, uninsulated..., bathtub, or lavatory). The proposed rule would define ``hand-held hair dryer'' as ``an electrical...

  18. Neurodevelopmental Versus Neurodegenerative Model of Schizophrenia and Bipolar Disorder: Comparison with Physiological Brain Development and Aging.

    Science.gov (United States)

    Buoli, Massimiliano; Serati, Marta; Caldiroli, Alice; Cremaschi, Laura; Altamura, Alfredo Carlo

    2017-03-01

    Available data support a contribution of both neurodevelopmental and neurodegenerative factors in the etiology of schizophrenia (SCH) and bipolar disorder (BD). Of note, one of the most important issue of the current psychiatric research is to identify the specific factors that contribute to impaired brain development and neurodegeneration in SCH and BD, and especially how these factors alter normal brain development and physiological aging process. Our hypothesis is that only specific damages, taking place in precise brain development stages, are associated with future SCH /BD onset and that neurodegeneration consists of an acceleration of brain aging after SCH /BD onset. In support of our hypothesis, the results of the present narrative mini-review shows as neurodevelopmental damages generally contribute to neuropsychiatric syndromes (e.g. hypothyroidism or treponema pallidum), but only some of them are specifically associated with adult SCH and BD (e.g. toxoplasma or substance abuse), particularly if they happen in specific stages of brain development. On the other hand, cognitive impairment and brain changes, associated with long duration of SCH /BD, look like what happens during aging: memory, executive domains and prefrontal cortex are implicated both in aging and in SCH /BD progression. Future research will explore possible validity of this etiological model for SCH and BD.

  19. Dopaminergic and cholinergic regulation of Fyn tyrosine kinase phosphorylation in the rat striatum in vivo.

    Science.gov (United States)

    Mao, Li-Min; Wang, John Q

    2015-12-01

    Src and Fyn are two Src family kinase (SFK) members that are expressed in mammalian brains and play important roles in the regulation of a variety of neuronal and synaptic substrates. Here we investigated the responsiveness of these SFKs to changing dopamine receptor signals in dopamine responsive regions of adult rat brains in vivo. Pharmacological activation of dopamine D1 receptors (D1Rs) by a systemic injection of the selective agonist SKF81297 increased phosphorylation of SFKs at a conserved and activation-associated autophosphorylation site (Y416) in the striatum, indicating activation of SFKs following SKF81297 injection. The dopamine D2 receptor (D2R) agonist quinpirole had no effect. Blockade of D1Rs with an antagonist SCH23390 did not alter striatal Y416 phosphorylation, while the D2R antagonist eticlopride elevated it. Between Src and Fyn, SKF81297 seemed to preferentially facilitate Fyn phosphorylation. Activation of muscarinic acetylcholine M4 receptors (M4Rs) with a positive allosteric modulator VU0152100 suppressed SFK Y416 responses to SKF81297. Additionally, SKF81297 induced a correlated increase in phosphorylation of N-methyl-D-aspartate (NMDA) receptor GluN2B subunits at a Fyn site (Y1472), which was attenuated by VU0152100. SKF81297 also enhanced synaptic recruitments of active Fyn and GluN1/GluN2B-containing NMDA receptors. These data demonstrate that D1Rs regulate Fyn and downstream NMDA receptors in striatal neurons in vivo. Acetylcholine through activating M4Rs inhibits Fyn and NMDA receptors in their sensitivity to D1R signaling. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. D1 dopamine receptor is involved in shell formation in larvae of Pacific oyster Crassostrea gigas.

    Science.gov (United States)

    Liu, Zhaoqun; Wang, Lingling; Yan, Yunchen; Zheng, Yan; Ge, Wenjing; Li, Meijia; Wang, Weilin; Song, Xiaorui; Song, Linsheng

    2018-07-01

    Dopamine (DA), a significant member of catecholamines, is reported to induce biomineralization of calcium carbonate vaterite microspheres via dopamine receptor (DR) in bivalves, implying the modulation of dopaminergic system on shell formation during larval development. In this research, a homologue of D1 type DR (CgD1DR-1) was identified from oyster Crassostrea gigas, whose full length cDNA was 1197 bp. It was widely expressed in various tissues of C. gigas, with the significantly higher levels in hepatopancreas, mantle, muscle and gill. During developmental stages, the mRNA transcripts of CgD1DR-1 in D-shape larvae were obviously higher (p < 0.05) than those in trochophore and umbo larvae, and CO 2 exposure could inhibit the synthesis of DA and mRNA expression of CgD1DR-1. After cell transfection and DA treatment, intracellular cAMP in cells with the expression of CgD1DR-1 increased significantly (p < 0.05). Furthermore, the incubation with SCH 23390 for the blockage of CgD1DR-1 significantly restrained the expressions of six shell formation-related genes including CgTyrosinase-1, CgTyrosinase-3, CgChitinaseLP, CgAMC, CgBMP and CgBMPR in trochophore and D-shape larvae. These results jointly suggested that DA together with its receptor CgD1DR-1 might be involved in shell formation during oyster larval development from trochophore to D-shape larvae, and CO 2 -induced ocean acidification (OA) might influence marine bivalves by inhibiting the DA-D1DR pathway to prohibit their shell formation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Sex differences in effects of dopamine D1 receptors on social withdrawal.

    Science.gov (United States)

    Campi, Katharine L; Greenberg, Gian D; Kapoor, Amita; Ziegler, Toni E; Trainor, Brian C

    2014-02-01

    Dopamine signaling in the nucleus accumbens (NAc) plays a critical role in the regulation of motivational states. Recent studies in male rodents show that social defeat stress increases the activity of ventral tegmental dopamine neurons projecting to the NAc, and that this increased activity is necessary for stress-induced social withdrawal. Domestic female mice are not similarly aggressive, which has hindered complementary studies in females. Using the monogamous California mouse (Peromyscus californicus), we found that social defeat increased total dopamine, DOPAC, and HVA content in the NAc in both males and females. These results are generally consistent with previous studies in Mus, and suggest defeat stress also increases NAc dopamine signaling in females. However, these results do not explain our previous observations that defeat stress induces social withdrawal in female but not male California mice. Pharmacological manipulations provided more insights. When 500 ng of the D1 agonist SKF38393 was infused in the NAc shell of females that were naïve to defeat, social interaction behavior was reduced. This same dose of SKF38393 had no effect in males, suggesting that D1 receptor activation is sufficient to induce social withdrawal in females but not males. Intra-accumbens infusion of the D1 antagonist SCH23390 increased social approach behavior in females exposed to defeat but not in females naïve to defeat. This result suggests that D1 receptors are necessary for defeat-induced social withdrawal. Overall, our results suggest that sex differences in molecular pathways that are regulated by D1 receptors contribute to sex differences in social withdrawal behavior. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Dopamine D1 receptors and phosphorylation of dopamine- and cyclic AMP-regulated phosphoprotein-32 in the medial preoptic area are involved in experience-induced enhancement of male sexual behavior in rats.

    Science.gov (United States)

    McHenry, Jenna A; Bell, Genevieve A; Parrish, Bradley P; Hull, Elaine M

    2012-08-01

    The medial preoptic area (MPOA) is an integral site for male sexual behavior. Dopamine is released in the MPOA before and during copulation and facilitates male rat sexual behavior. Repeated sexual experience and noncopulatory exposures to an estrous female facilitate subsequent copulation. However, the neurobiological mechanisms that mediate such enhancement remain unclear. Here, we examined the role of dopamine D₁ receptors in the MPOA in experience-induced enhancement of male sexual behavior in rats. In experiment 1, microinjections of the D₁ antagonist SCH-23390 into the MPOA before each of seven daily 30-min noncopulatory exposures to a receptive female impaired copulation on a drug-free test on Day 8, compared to vehicle-treated female-exposed animals. Copulatory performance in drug-treated animals was similar to that of vehicle-treated males that had not been preexposed to females. This effect was site specific. There were no group differences in locomotor activity in an open field on the copulation test day. In experiment 2, a separate cohort of animals was used to examine phosphorylation of dopamine- and cAMP-regulated phosphoprotein (DARPP-32) in the MPOA of animals with acute and/or chronic sexual experience. DARPP-32 is a downstream marker of D₁ receptor signaling and substrate of cAMP-dependent protein kinase (PKA). Western immunoblot analysis revealed that p-DARPP-32 expression was greatest in the MPOA of males that received both acute and chronic sexual experience, compared to all other mated conditions and naïve controls. These data suggest that D₁ receptors in the MPOA contribute to experience-induced enhancement of male sexual behavior, perhaps through a PKA regulated mechanism.

  3. Extinction memory is facilitated by methylphenidate and regulated by dopamine and noradrenaline receptors.

    Science.gov (United States)

    Furini, Cristiane R G; Behling, Jonny A K; Zinn, Carolina G; Zanini, Mara Lise; Assis Brasil, Eduardo; Pereira, Luiza Doro; Izquierdo, Ivan; de Carvalho Myskiw, Jociane

    2017-05-30

    Extinction is defined as the learned inhibition of retrieval and is the mainstay of exposure therapy, which is widely used to treat drug addiction, phobias and fear disorders. The psychostimulant, methylphenidate (MPH) is known to increase extracellular levels of noradrenaline and dopamine by blocking their reuptake and studies have demonstrated that MPH can modulate hippocampal physiology and/or functions including long-term potentiation (LTP), learning and memory. However, the influence of MPH on fear extinction memory has been insufficiently studied. Here we investigate the effect of MPH infused into the CA1 region of the hippocampus on extinction memory in animals normally incapable of showing contextual fear conditioning (CFC) extinction because of weak training, and the possible mechanisms through which it acts during this process. For this, male Wistar rats with infusion cannulae stereotaxically implanted in the CA1 region were submitted to a weak extinction protocol in a CFC apparatus. Animals that received intra-CA1 infusion of MPH (12.5μg/side) 20min before the extinction training (Ext Tr) expressed less freezing behavior than Veh-treated animals during both Ext Tr and extinction retention Test (Ext Test). Additionally, the administration of MPH+Timolol (1μg/side) or MPH+SCH23390 (1.5μg/side) intra-CA1 20min before the Ext Tr blocked the enhancing effect of the MPH on extinction learning. These results suggest that MPH in the CA1 region of the hippocampus is able to induce the consolidation of extinction memory and this process occurs through both β-adrenergic and D1/D5 dopaminergic receptors. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Ghrelin increases the motivation to eat, but does not alter food palatability

    Science.gov (United States)

    Overduin, Joost; Figlewicz, Dianne P.; Bennett-Jay, Jennifer; Kittleson, Sepideh

    2012-01-01

    Homeostatic eating cannot explain overconsumption of food and pathological weight gain. A more likely factor promoting excessive eating is food reward and its representation in the central nervous system (CNS). The anorectic hormones leptin and insulin reduce food reward and inhibit related CNS reward pathways. Conversely, the orexigenic gastrointestinal hormone ghrelin activates both homeostatic and reward-related neurocircuits. The current studies were conducted to identify in rats the effects of intracerebroventricular ghrelin infusions on two distinct aspects of food reward: hedonic valuation (i.e., “liking”) and the motivation to self-administer (i.e., “wanting”) food. To assess hedonic valuation of liquid food, lick motor patterns were recorded using lickometry. Although ghrelin administration increased energy intake, it did not alter the avidity of licking (initial lick rates or lick-cluster size). Several positive-control conditions ruled out lick-rate ceiling effects. Similarly, when the liquid diet was hedonically devalued with quinine supplementation, ghrelin failed to reverse the quinine-associated reduction of energy intake and avidity of licking. The effects of ghrelin on rats' motivation to eat were assessed using lever pressing to self-administer food in a progressive-ratio paradigm. Ghrelin markedly increased motivation to eat, to levels comparable to or greater than those seen following 24 h of food deprivation. Pretreatment with the dopamine D1 receptor antagonist SCH-23390 eliminated ghrelin-induced increases in lever pressing, without compromising generalized licking motor control, indicating a role for D1 signaling in ghrelin's motivational feeding effects. These results indicate that ghrelin increases the motivation to eat via D1 receptor-dependent mechanisms, without affecting perceived food palatability. PMID:22673784

  5. Blockade of group II metabotropic glutamate receptors produces hyper-locomotion in cocaine pre-exposed rats by interactions with dopamine receptors.

    Science.gov (United States)

    Yoon, Hyung Shin; Jang, Ju Kyong; Kim, Jeong-Hoon

    2008-09-01

    It was previously reported that blockade of group II metabotropic glutamate receptors (mGluRs) produces hyper-locomotion in rats previously exposed to amphetamine, indicating that group II mGluRs are well positioned to modulate the expression of behavioral sensitization by amphetamine. The present study further examined the locomotor activating effects of specific blockade of these receptors after cocaine pre-exposures. First, rats were pre-exposed to seven daily injections of cocaine (15mg/kg, IP). When challenged the next day with an injection of either saline or the group II mGluR antagonist LY341495 (0.5, 1.0 or 2.5mg/kg, IP), they produced hyper-locomotor activity, measured by infrared beam interruptions, to LY341495 compared to saline in a dose-dependent manner. Second, rats were pre-exposed to either saline or seven daily injections of cocaine (15mg/kg, IP). Three weeks later, when they were challenged with an injection of either saline or LY341495 (1.0mg/kg, IP), only rats pre-exposed to cocaine produced hyper-locomotor activity to LY341495 compared to saline. These effects, however, were not present when dopamine D1 (SCH23390; 5 or 10microg/kg), but not D2 (eticlopride; 10 or 50microg/kg), receptor antagonist was pre-injected, indicating that this cocaine-induced hyper-locomotor activity to LY341495 may be mediated in dopamine D1 receptor-dependent manner. These results suggest that group II mGluRs may be adapted to interact with dopaminergic neuronal signaling in mediating the sensitized locomotor activity produced by repeated cocaine pre-exposures.

  6. Investigation of the mechanisms mediating MDMA "Ecstasy"-induced increases in cerebro-cortical perfusion determined by btASL MRI.

    Science.gov (United States)

    Rouine, J; Kelly, M E; Jennings-Murphy, C; Duffy, P; Gorman, I; Gormley, S; Kerskens, C M; Harkin, Andrew

    2015-05-01

    Acute administration of the recreational drug of abuse 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) has previously been shown to increase cerebro-cortical perfusion as determined by bolus-tracking arterial spin labelling (btASL) MRI. The purpose of the current study was to assess the mechanisms mediating these changes following systemic administration of MDMA to rats. Pharmacological manipulation of serotonergic, dopaminergic and nitrergic transmission was carried out to determine the mechanism of action of MDMA-induced increases in cortical perfusion using btASL MRI. Fenfluramine (10 mg/kg), like MDMA (20 mg/kg), increased cortical perfusion. Increased cortical perfusion was not obtained with the 5-HT2 receptor agonist 2,5-dimethoxy-4-iodophenyl-aminopropane hydrochloride (DOI) (1 mg/kg). Depletion of central 5-HT following systemic administration of the tryptophan hydroxylase inhibitor para-chlorophenylalanine (pCPA) produced effects similar to those observed with MDMA. Pre-treatment with the 5-HT receptor antagonist metergoline (4 mg/kg) or with the 5-HT reuptake inhibitor citalopram (30 mg/kg), however, failed to produce any effect alone or influence the response to MDMA. Pre-treatment with the dopamine D1 receptor antagonist SCH 23390 (1 mg/kg) failed to influence the changes in cortical perfusion obtained with MDMA. Treatment with the neuronal nitric oxide (NO) synthase inhibitor 7-nitroindazole (7-NI) (25 mg/kg) provoked no change in cerebral perfusion alone yet attenuated the MDMA-related increase in cortical perfusion. Cortical 5-HT depletion is associated with increases in perfusion although this mechanism alone does not account for MDMA-related changes. A role for NO, a key regulator of cerebrovascular perfusion, is implicated in MDMA-induced increases in cortical perfusion.

  7. Pharmacologic MRI (phMRI) as a tool to differentiate Parkinson's disease-related from age-related changes in basal ganglia function.

    Science.gov (United States)

    Andersen, Anders H; Hardy, Peter A; Forman, Eric; Gerhardt, Greg A; Gash, Don M; Grondin, Richard C; Zhang, Zhiming

    2015-02-01

    The prevalence of both parkinsonian signs and Parkinson's disease (PD) per se increases with age. Although the pathophysiology of PD has been studied extensively, less is known about the functional changes taking place in the basal ganglia circuitry with age. To specifically address this issue, 3 groups of rhesus macaques were studied: normal middle-aged animals (used as controls), middle-aged animals with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism, and aged animals (>20 years old) with declines in motor function. All animals underwent the same behavioral and pharmacologic magnetic resonance imaging (phMRI) procedures to measure changes in basal ganglia function in response to dopaminergic drug challenges consisting of apomorphine administration followed by either a D1 (SCH23390) or a D2 (raclopride) receptor antagonist. Significant functional changes were predominantly seen in the external segment of the globus pallidus (GPe) in aged animals and in the striatum (caudate nucleus and putamen) in MPTP-lesioned animals. Despite significant differences seen in the putamen and GPe between MPTP-lesioned versus aged animals, a similar response profile to dopaminergic stimulations was found between these 2 groups in the internal segment of the GP. In contrast, the pharmacologic responses seen in the control animals were much milder compared with the other 2 groups in all the examined areas. Our phMRI findings in MPTP-lesioned parkinsonian and aged animals suggest that changes in basal ganglia function in the elderly may differ from those seen in parkinsonian patients and that phMRI could be used to distinguish PD from other age-associated functional alterations in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Antidepressant drugs specifically inhibiting noradrenaline reuptake enhance recognition memory in rats.

    Science.gov (United States)

    Feltmann, Kristin; Konradsson-Geuken, Åsa; De Bundel, Dimitri; Lindskog, Maria; Schilström, Björn

    2015-12-01

    Patients suffering from major depression often experience memory deficits even after the remission of mood symptoms, and many antidepressant drugs do not affect, or impair, memory in animals and humans. However, some antidepressant drugs, after a single dose, enhance cognition in humans (Harmer et al., 2009). To compare different classes of antidepressant drugs for their potential as memory enhancers, we used a version of the novel object recognition task in which rats spontaneously forget objects 24 hr after their presentation. Antidepressant drugs were injected systemically 30 min before or directly after the training phase (Session 1 [S1]). Post-S1 injections were used to test for specific memory-consolidation effects. The noradrenaline reuptake inhibitors reboxetine and atomoxetine, as well as the serotonin noradrenaline reuptake inhibitor duloxetine, injected prior to S1 significantly enhanced recognition memory. In contrast, the serotonin reuptake inhibitors citalopram and paroxetine and the cyclic antidepressant drugs desipramine and mianserin did not enhance recognition memory. Post-S1 injection of either reboxetine or citalopram significantly enhanced recognition memory, indicating an effect on memory consolidation. The fact that citalopram had an effect only when injected after S1 suggests that it may counteract its own consolidation-enhancing effect by interfering with memory acquisition. However, pretreatment with citalopram did not attenuate reboxetine's memory-enhancing effect. The D1/5-receptor antagonist SCH23390 blunted reboxetine's memory-enhancing effect, indicating a role of dopaminergic transmission in reboxetine-induced recognition memory enhancement. Our results suggest that antidepressant drugs specifically inhibiting noradrenaline reuptake enhance cognition and may be beneficial in the treatment of cognitive symptoms of depression. (c) 2015 APA, all rights reserved).

  9. Radiopharmaceuticals in positron emission tomography: Radioisotope productions and radiolabelling procedures at the Austin and Repatriation Medical Centre

    International Nuclear Information System (INIS)

    Tochon-Danguy, H.J.; Sachinidis, J.I.; Chan, J.G.; Cook, M.

    1997-01-01

    Positron Emission Tomography (PET) is a technique that utilizes positron-emitting radiopharmaceuticals to map the physiology, biochemistry and pharmacology of the human body. Positron-emitting radioisotopes produced in a medical cyclotron are incorporated into compounds that are biologically active in the body. A scanner measures radioactivity emitted from a patient's body and provides cross-sectional images of the distribution of these radiolabelled compounds in the body. It is the purpose of this paper to review the variety of PET radiopharmaceuticals currently produced at the Austin and Repatriation Medical Centre in Melbourne. Radioisotope production, radiolabelling of molecules and quality control of radiopharmaceuticals will be discussed. A few examples of their clinical applications will be shown as well. During the last five years we achieved a reliable routine production of various radiopharmaceuticals labelled with the four most important positron-emitters: oxygen-15 (t, 1/2 =2min), nitrogen-13 (t 1/2 = 10 min), carbon-11 (t 1/2 =20 min) and fluorine-18 (t 1/2 = 110 min). These radiopharmaceuticals include [ 15 O]oxygen, [ 15 O]carbon monoxide, [ 15 O]carbon dioxide, [ 15 O]water, [ 13 N]ammonia, [ 11 C]flumazenil, [ 11 C]SCH23390, [ 18 F]fluoromisonidazole and [ 18 F]fluoro-deoxy-glucose ([ 18 F]FDG). In addition, since the half life of [ 18 F] is almost two hours, regional distribution can be done, and the Austin and Repatriation Medical Centre is currently supplying [ 18 F]FDG in routine to other hospitals. Future new radiopharmaceuticals development include a [ 18 F]thymidine analog to measure cell proliferation and a [ 11 C]pyrroloisoquinoline to visualize serotonergic neuron abnormalities. (authors)

  10. Dopamine dysregulation hypothesis: the common basis for motivational anhedonia in major depressive disorder and schizophrenia?

    Science.gov (United States)

    Szczypiński, Jan Józef; Gola, Mateusz

    2018-03-24

    Abnormalities in reward processing are crucial symptoms of major depressive disorder (MDD) and schizophrenia (SCH). Recent neuroscientific findings regarding MDD have led to conclusions about two different symptoms related to reward processing: motivational and consummatory anhedonia, corresponding, respectively, to impaired motivation to obtain rewards ('wanting'), and diminished satisfaction from consuming them ('liking'). One can ask: which of these is common for MDD and SCH. In our review of the latest neuroscientific studies, we show that MDD and SCH do not share consummatory anhedonia, as SCH patients usually have unaltered liking. Therefore, we investigated whether motivational anhedonia is the common symptom across MDD and SCH. With regard to the similarities and differences between the neural mechanisms of MDD and SCH, here we expand the current knowledge of motivation deficits and present the common underlying mechanism of motivational anhedonia - the dopamine dysregulation hypothesis - stating that any prolonged dysregulation in tonic dopamine signaling that exceeds the given equilibrium can lead to striatal dysfunction and motivational anhedonia. The implications for further research and treatment of MDD and SCH are also discussed.

  11. Spindle Cell Hemangioendothelioma of the Temporal Muscle Resected with Zygomatic Osteotomy: A Case Report of an Unusual Intramuscular Lesion Mimicking Sarcoma

    Directory of Open Access Journals (Sweden)

    Tomohiro Minagawa

    2011-01-01

    Full Text Available Spindle cell hemangioendothelioma (SCH was originally described by Weiss and Enzinger (1986 as a low-grade angiosarcoma resembling both cavernous hemangioma and Kaposi's sarcoma. Recent studies suggest that SCH is a benign neoplasm or reactive lesion accompanying a congenital or acquired vascular malformation. Most SCHs present as one or more nodules affecting the dermis or subcutis of the distal extremities. Few reports describe SCH of the head and neck region; even fewer note intramuscular SCH. Here, we describe a case of SCH involving the temporal muscle mimicking soft tissue sarcoma, who had a successful surgical treatment with a coronal approach and zygomatic osteotomy.

  12. Thyroid exposure of Belarusian and Ukrainian children due to the Chernobyl accident and resulting thyroid cancer risk. Final report of BfS project StSch 4240

    Energy Technology Data Exchange (ETDEWEB)

    Jacob, P; Meckbach, R; Ulanovski, A; Schotola, C; Proehl, G [GSF-Institute of Radiation Protection, Neuherberg (Germany); Kenigsberg, J; Buglova, E; Kruk, J [Institute of Radiation Medicine and Endocrinology, Minsk (Belarus); Likhtarev, I; Kovgan, L; Vavilov, S; Chepurniy, M [Ukrainian Radiation Protection Inst., Kyiv (Ukraine); Tronko, M; Bogdanova, T [Institute of Endocrinolgoy and Metabolism of the Academy of Medical Sciences of Ukraine, Kyiv (Ukraine); Shinkarev, S; Gavrilin, Y [All-Russian Public Organization of Invalids ' Chernobylets' , Scientific Center ' FENIX' , Moscow (Russian Federation); Demidchik, Y [Thyroid Cancer Center, Minsk (Belarus)

    2005-07-01

    Main objectives of the BfS Project StSch4240 Thyroid Exposure of Belarusian and Ukrainian Children due to the Chernobyl Accident and Resulting Thyroid Cancer Risk were: to establish improved estimates of average thyroid dose for both genders and for each birth-year cohort of the period 1968 - 1985 in Ukrainian and Belarusian settlements, in which more than 10 measurements of the {sup 131}I activity in the human thyroid have been performed in May/June 1986, to explore, whether this dosimetric database can be extended to neighboring settlements, to establish improved estimates of average thyroid dose for both genders and for each birth-year cohort of the period 1968 - 1985 in Ukrainian and Belarusian oblasts (regions) and larger cities, to document the thyroid cancer incidence for the period 1986 - 2001 in Ukraine and Belarus and describe morphological characteristics of the cancer cases, to assess the contribution of the baseline incidence to the total thyroid cancer incidence in the two countries and identify regional and temporal dependencies, to perform analyses of excess risks in settlements with more than 10 measurements of the {sup 131}I activity in the human thyroid. The project has been conducted in the period 6 December 1999 to 31 March 2004. (orig.)

  13. Thyroid exposure of Belarusian and Ukrainian children due to the Chernobyl accident and resulting thyroid cancer risk. Final report of BfS project StSch 4240

    International Nuclear Information System (INIS)

    Jacob, P.; Meckbach, R.; Ulanovski, A.; Schotola, C.; Proehl, G.; Kenigsberg, J.; Buglova, E.; Kruk, J.; Likhtarev, I.; Kovgan, L.; Vavilov, S.; Chepurniy, M.; Tronko, M.; Bogdanova, T.; Shinkarev, S.; Gavrilin, Y.; Demidchik, Y.

    2005-01-01

    Main objectives of the BfS Project StSch4240 Thyroid Exposure of Belarusian and Ukrainian Children due to the Chernobyl Accident and Resulting Thyroid Cancer Risk were: to establish improved estimates of average thyroid dose for both genders and for each birth-year cohort of the period 1968 - 1985 in Ukrainian and Belarusian settlements, in which more than 10 measurements of the 131 I activity in the human thyroid have been performed in May/June 1986, to explore, whether this dosimetric database can be extended to neighboring settlements, to establish improved estimates of average thyroid dose for both genders and for each birth-year cohort of the period 1968 - 1985 in Ukrainian and Belarusian oblasts (regions) and larger cities, to document the thyroid cancer incidence for the period 1986 - 2001 in Ukraine and Belarus and describe morphological characteristics of the cancer cases, to assess the contribution of the baseline incidence to the total thyroid cancer incidence in the two countries and identify regional and temporal dependencies, to perform analyses of excess risks in settlements with more than 10 measurements of the 131 I activity in the human thyroid. The project has been conducted in the period 6 December 1999 to 31 March 2004. (orig.)

  14. Evaluation of Emissions Declarations according to 11. BimSchV of the year 2004 for the use of emissions reporting at UNFCCC and UNECE. Stationary internal combustion engines; Aufbereitung von Daten der Emissionserklaerungen gemaess 11. BImSchV aus dem Jahre 2004 fuer die Verwendung bei der UNFCCC- und UNECE-Berichterstattung. Teilbericht Stationaere Verbrennungsmotoren

    Energy Technology Data Exchange (ETDEWEB)

    Degel, Melanie; Joerss, Wolfram [IZT Institut fuer Zukunftsstudien und Technologiebewertung, Berlin (Germany)

    2009-12-15

    The Emissions Declarations according to 11{sup th} BImSchV from 2004 for stationary internal combustion engines were analysed with the aim to derive fuel specific emission factors for a set of air pollutants and greenhouse gases. For that purpose, curtly 1.000 plants have been identified which on one hand are operated with exactly one fuel (no fuel mixing) and on the other hand technologically solely consist of internal combustion engines (no peak boilers). During extensive checks of plausibility, 80 - 95% of the data sets were rejected, depending on pollutant and fuel. Nonetheless, very high fluctuation ranges for specific emissions were found in the remaining data material. As the result, emission factors have been derived for the pollutants NO{sub x}, CO, SO{sub 2}, formaldehyde, total dust, methane, B(a)P, benzene and total-C without Methane and for the fuels natural gas, landfill gas, digester gas, biogas, mine gas, light fuel oil/diesel oil and plant oil. The uncertainties of the derived emission factors are between {+-} 15% and two orders of magnitude. No or no resilient data have been found for the pollutants NH{sub 3}, N{sub 2}O, NMVOC, particulate matter PM{sub 2.5}/PM{sub 10} and soot as well as for the fuels Plant oil ester and wood gas. (orig.)

  15. Carbon and nitrogen fluxes in the North Indian Ocean

    Digital Repository Service at National Institute of Oceanography (India)

    Naqvi, S.W.A.; Naik, H.; DeSouza, W.; Narvekar, P.V.; Paropkari, A.L.; Bange, H.W.

    , the reverse is probably true for the burial. Notwithstanding these uncertainties, it seems reasonable to conclude that the POC delivery by rivers substantially exceeds sedimentary organic carbon burial in the NEIO. In spite of the higher sedimentation... in the NEIO has been reported to range from 0.3 to 2.5 (average 1.4) Tg N yr -1 (Schäfer et al., 1993). This is slightly higher than the DIN delivery by rivers. Rate of N 2 -fixation in the NEIO has not been measured so far. However, it is probably much...

  16. 75 FR 64683 - Liability for Termination of Single-Employer Plans; Treatment of Substantial Cessation of Operations

    Science.gov (United States)

    2010-10-20

    ... Termination of Single-Employer Plans; Treatment of Substantial Cessation of Operations AGENCY: Pension Benefit... cessations of operations by employers that maintain single-employer plans. DATES: Comments must be submitted... 4062(e), which provides for reporting of and liability for certain substantial cessations of operations...

  17. Alteration in intrinsic and extrinsic functional connectivity of resting state networks associated with subclinical hypothyroid.

    Science.gov (United States)

    Kumar, Mukesh; Modi, Shilpi; Rana, Poonam; Kumar, Pawan; Kanwar, Ratnesh; Sekhri, Tarun; D'souza, Maria; Khushu, Subash

    2018-03-05

    Subclinical hypothyroidism (SCH) is characterized by mild elevation of thyroid stimulating hormone (TSH) (range 5-10 μIU/ml) and normal free triiodothyronine (FT3) and free thyroxine (FT4). The cognitive function impairment is well known in thyroid disorders such as hypothyroidism and hyperthyroidism, but little is known about deficits in brain functions in SCH subjects. Also, whether hormone-replacement treatment is necessary or not in SCH subjects is still debatable. In order to have an insight into the cognition of SCH subjects, intrinsic and extrinsic functional connectivity (FC) of the resting state networks (RSNs) was studied. For resting state data analysis we used an unbiased, data-driven approach based on Independent Component Analysis (ICA) and dual-regression that can emphasize widespread changes in FC without restricting to a set of predefined seeds. 28 SCH subjects and 28 matched healthy controls (HC) participated in the study. RSN analysis showed significantly decreased intrinsic FC in somato-motor network (SMN) and right fronto-parietal attention network (RAN) and increased intrinsic FC in default mode network (DMN) in SCH subjects as compared to control subjects. The reduced intrinsic FC in the SMN and RAN suggests neuro-cognitive alterations in SCH subjects in the corresponding functions which were also evident from the deficit in the neuropsychological performance of the SCH subjects on behavioural tests such as digit span, delayed recall, visual retention, recognition, Bender Gestalt and Mini-Mental State Examination (MMSE). We also found a significant reduction in extrinsic network FC between DMN and RAN; SMN and posterior default mode network (PDMN); and increased extrinsic FC between SMN and anterior default mode network (ADMN) in SCH subjects as compared to controls. An altered extrinsic FC in SCH suggests functional reorganization in response to neurological disruption. The partial correlation analysis between intrinsic and extrinsic RSNs

  18. Downsizing of a provincial department of health--causes and implications for fiscal policy.

    Science.gov (United States)

    Blecher, Mark

    2002-06-01

    To analyse the financial basis for downsizing of a provincial health department and suggest implications for fiscal policy. Analysis of relevant departmental, provincial and national financing and expenditure trends from 1995/96 to 2002/03. Western Cape (WC) Department of Health (DOH). Downsizing involving 9,282 health workers (27.9%) and closure of 3,601 hospital beds (24.4%) over 5 years. Total aggregate provincial transfers (all provinces) remained fairly constant in real terms. The WC's share decreased from 11.8% in 1996/97 to 9.8% in 2002/03. This was offset by the DOH's share of the WC budget increasing from 25.6% to 29.6%, mainly because of an increase in national health conditional grants. The net effect of financing changes was that the DOH's allocation in real terms was similar in 2002/03 and 1995/96, which suggests that financing changes are not the major cause of downsizing. Expenditure analysis revealed a 39.7% real rise in the average cost of health personnel. Substantial interprovincial inequities remain. The major cause of downsizing was wage growth, particularly following the 1996 wage agreement. Disjointed fiscal and wage policy has affected health services. Simultaneous application of policies of fiscal constraint, redistribution and substantial real wage growth has resulted in substantial downsizing with limited inroads into inequities. Inequities will continue to call for further redistribution, reduction in conditional grants and downsizing, much of which could have been avoided if fiscal and wage policy choices had been optimal.

  19. Grammatical Conception of Yuriy Shevel'ov: Nominative ↔ Vocative in the System of Substantial Categoriality

    Directory of Open Access Journals (Sweden)

    Anatoliy Zahnitko

    2016-08-01

    Full Text Available Background. Analysis of Yuriy Shevel'ov’s approaches to the interpretation of the morphological tier of language, as well as his examination of particular phenomena of this level – substantiality, verbality, and others – reflects not only the author's understanding itself of all the grammatical system as a whole, and morphological one in particular, but also represents the features of modification of scientific approaches in the history of linguistic thought of mid-twentieth century, its strengthening in the studies of the XX – XXI century. The researcher’s definition of nominative and vocative cases as interrelated within the categorical substantiality is of particular importance. Purpose: to determine the main components of interpretation of the status dimension of the nominative and vocative cases within morpho-substantial categoriality of Yuriy Shevel'ov with the definition of theoretical foundations and practical principles, revealing the patterns of establishing internal sentence dimension of the nominative and vocative cases. Results: In the case theory with reliance on the sequence of forms of dependencies in the internal sentence space Yuriy Shevel'ov distinguishes five cases: genitive, dative, accusative, ablative, locative. In the statement about the nominative as grammatically independent case the scientist relies on sentence. Two-dimensionality of grammatically independent case opposes to the one-dimensional grammatically dependent nominative that is traceable in syntactic positions of predicate and apposition. Yuriy Shevel'ov did not consider addressing that is not grammatically linked to the sentence with a specific expression as an individual case. The forms of vocative case show functional three-componentity, because in its functional-semantic paradigm it covers the function of the addressee – potential subject of action (primary function that is represented in formal grammar sentence structure by the main element of

  20. Clozapine-induced dysphagia with secondary substantial weight loss.

    Science.gov (United States)

    Osman, Mugtaba; Devadas, Vekneswaran

    2016-08-19

    Dysphagia is listed as a 'rare' side effect following clozapine treatment. In this case report, we describe how significant clozapine-induced dysphagia has led to significant reduction of nutritional intake with subsequent substantial weight loss. An 18-year-old single man with an established diagnosis of treatment-resistant paranoid schizophrenia recovered well on a therapeutic dose of clozapine. However, he was noted to lose weight significantly (up to 20% of his original weight) as the dose was uptitrated. This was brought about by development of dysphagia, likely to be due to clozapine. Addition of nutritional supplementary liquids and initiation of a modified behavioural dietary/swallowing programme, while repeatedly mastering the Mendelsohn manoeuvre technique, alleviated the swallowing difficulties and restored his weight. 2016 BMJ Publishing Group Ltd.

  1. Subclinical hypothyroidism and mortality in a large Austrian cohort: a possible impact on treatment?

    Science.gov (United States)

    Kovar, Florian Maria; Fang, I-Fei; Perkmann, Thomas; Haslacher, Helmuth; Slavka, Georg; Födinger, Manuela; Endler, Georg; Wagner, Oswald F

    2015-12-01

    Clinical implications of subclinical hypothyroidism (SCH) are still matter of intense debate, resulting in the controversial discussion whether subclinical hypothyroidism should be treated. We performed a cohort study to evaluate the impact of subclinical hypothyroidism on vascular and overall mortality. Between 02/1993 and 03/2004, a total of 103,135 persons attending the General Hospital Vienna with baseline serum thyrotropin (TSH, thyroid-stimulating hormone) and free thyroxin (fT4) measurements could be enrolled in a retrospective cohort study. Subclinical hypothyroidism was defined by elevated TSH ranging from 4.5 to 20.0 mIU/L and normal fT4 concentration (0.7-1.7 ng/dL). Overall and vascular mortality as primary endpoints were assessed via record linkage with the Austrian Death Registry. A total of 80,490 subjects fulfilled inclusion criteria of whom 3934 participants (3.7%) were classified as SCH (868 males and 3066 females, median age 48 years). The mean follow-up among the 80,490 subjects was 4.1 years yielding an observation period of 373,301 person-years at risk. In a multivariate Cox regression model adjusted for age and gender TSH levels showed a dose-dependent association with all-cause mortality. The association between SCH and overall or vascular mortality was stronger in men below 60 years compared to older males or females. Our data support the hypothesis that SCH might represent an independent risk factor for overall and vascular mortality, especially in men below 60 years. Whether this group would benefit from replacement therapy should be evaluated in interventional studies.

  2. Individual-based assessment of population structure and admixture in Austrian, Croatian and German draught horses.

    Science.gov (United States)

    Druml, T; Curik, I; Baumung, R; Aberle, K; Distl, O; Sölkner, J

    2007-02-01

    All over Europe, the number of draught horses has decreased drastically during the last 50 years. As a prerequisite for efficient management decisions, we analysed the conservation status in Austrian (Noriker Carinthia - NC, Noriker Salzburg - NS), Croatian (Croatian Coldblood - C, Posavina horse - P) and German (Altmaerkisch Coldblood - A, Black Forest horse - BF, Mecklenburg Coldblood - M, Rhenish German Draught horse - R, Saxon Thuringa Coldblood - ST, Schleswig Draught horse - Sch, South German Coldblood - SG) draught horses (434) using multilocus genotypic information from 30 (effectively 27) microsatellite loci. Populations located in areas with less intensive agricultural production (C, NC, NS, P and SG) had greater diversity within the population and estimated effective population size than A, BF, Sch, M, R and ST populations. The PCA plots revealed that populations form five separate groups. The 'Noriker' group (NC, NS and SG) and the 'Rhenish' group (A, M, R and ST) were the most distinctive (pairwise F(ST) values ranged from 0.078 to 0.094). The 'Croatian' group (C and P) was in the centre, while the BF and Sch populations formed two out-groups. A posterior Bayesian analysis detected further differentiation, mainly caused by political and geographical factors. Thus, it was possible to separate the South German Coldblood from the Austrian Noriker population where no subpopulation structure was detected. The admixture analysis revealed imprecise classification between C and P populations. A small but notable separation of R from A, M and ST populations was detected, while Sch and BF populations remained as out-groups. The information obtained should aid in making efficient conservation decisions.

  3. Initial substantial reduction in air dose rates of Cs origin and personal doses for residents owing to the Fukushima nuclear accident

    International Nuclear Information System (INIS)

    Yoshida, Hiroko; Saito, Junko; Hirasawa, Noriyasu; Kobayashi, Ikuo

    2013-01-01

    The initial substantial reduction in the air dose rate and personal dose equivalent [Hp(10)] for residents were compared between the Marumori and Kosugo regions for the period from September 2011 to September 2012 after the occurrence of the Fukushima nuclear accident. Marumori is a rural settlement, and Kosugo is a suburban city along a freeway. A similar tendency was observed in the Hp(10) results for Marumori residents and in the air dose rates for both regions: values dropped during the heavy snow season and a faster reduction in the air dose rate than the radioactive decay of 134 Cs and 137 Cs was observed after the snow had thawed. These reductions are considered to be caused by the weathering and/or migration of radionuclides down the soil column. However, neither a drop due to an accumulation of snow nor faster reduction was observed in Hp(10) for Kosugo residents. This discrepancy between the air dose rate and Hp(10) for Marumori and Kosugo residents might be caused by differences in their living environment. (author)

  4. Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death

    DEFF Research Database (Denmark)

    Nyegaard, Mette; Overgaard, Michael Toft; Sondergaard, M.T.

    2012-01-01

    a substantial part of sudden cardiac deaths in young individuals. Mutations in RYR2, encoding the cardiac sarcoplasmic calcium channel, have been identified as causative in approximately half of all dominantly inherited CPVT cases. Applying a genome-wide linkage analysis in a large Swedish family with a severe......Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a devastating inherited disorder characterized by episodic syncope and/or sudden cardiac arrest during exercise or acute emotion in individuals without structural cardiac abnormalities. Although rare, CPVT is suspected to cause...... calmodulin-binding-domain peptide at low calcium concentrations. We conclude that calmodulin mutations can cause severe cardiac arrhythmia and that the calmodulin genes are candidates for genetic screening of individual cases and families with idiopathic ventricular tachycardia and unexplained sudden cardiac...

  5. Leakage Characteristics of Dual-Cannula Fenestrated Tracheostomy Tubes during Positive Pressure Ventilation: A Bench Study

    Directory of Open Access Journals (Sweden)

    Thomas Berlet

    2016-01-01

    Full Text Available This study compared the leakage characteristics of different types of dual-cannula fenestrated tracheostomy tubes during positive pressure ventilation. Fenestrated Portex® Blue Line Ultra®, TRACOE® twist, or Rüsch® Traceofix® tracheostomy tubes equipped with nonfenestrated inner cannulas were tested in a tracheostomy-lung simulator. Transfenestration pressures and transfenestration leakage rates were measured during positive pressure ventilation. The impact of different ventilation modes, airway pressures, temperatures, and simulated static lung compliance settings on leakage characteristics was assessed. We observed substantial differences in transfenestration pressures and transfenestration leakage rates. The leakage rates of the best performing tubes were <3.5% of the delivered minute volume. At body temperature, the leakage rates of these tracheostomy tubes were <1%. The tracheal tube design was the main factor that determined the leakage characteristics. Careful tracheostomy tube selection permits the use of fenestrated tracheostomy tubes in patients receiving positive pressure ventilation immediately after stoma formation and minimises the risk of complications caused by transfenestration gas leakage, for example, subcutaneous emphysema.

  6. A new approach for simple radioisotope cisternography examination in cerebrospinal fluid leakage detection.

    Science.gov (United States)

    Hoshino, Hiromitsu; Higuchi, Tetsuya; Achmad, Arifudin; Taketomi-Takahashi, Ayako; Fujimaki, Hiroya; Tsushima, Yoshito

    2016-01-01

    We developed a new quantitative interpretation technique of radioisotope cisternography (RIC) for the diagnosis of spontaneous cerebrospinal fluid hypovolemia (SCH). RIC studies performed for suspected SCH were evaluated. (111)In-DTPA RIC images were taken at 0, 1, 3, 6, and 24-h after radioisotope injection following the current protocol. Regions of interest (ROI) were selected on 3-h images to include brain, spine, bladder or the whole body. The accumulative radioactivity counts were calculated for quantitative analysis. Final diagnoses of SCH were established based on the diagnostic criteria recently proposed by Schievink and colleagues. Thirty-five patients were focused on. Twenty-one (60.0%) patients were diagnosed as having SCH according to the Schievink criteria. On the 3-h images, direct cerebrospinal fluid leakage sign was detected in nine of 21 SCH patients (42.9%), as well as three patients with suspected iatrogenic leakage. Compared to non-SCH patients, SCH patients showed higher bladder accumulation at 3-h images (P = 0.0002), and higher brain clearance between the 6- and 24-h images (P leakage was not observed. 1- and 6-h images did not provide any additional information in any patients. A new simple ROI setting method, in which only the 3-h whole body and 24-h brain images were necessary, was sufficient to diagnose SCH.

  7. EFSA Panel on Di etetic Products, Nutrition and Allergie s (NDA); Scientific Opinion on the substantiation of a health claim relate d to OXY 280 and reduction of body weight pur suant to Article 13(5) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    Following an application from Actina, submitted pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Belgium, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related...... relative to the placebo, and that no conclusions can be drawn from this study for the scientific substantiation of the claim. The Panel notes that no studies from which conclusions could be drawn for the scientific substantiation of the claim were provided by the applicant. The Panel concludes that a cause...

  8. SUBCLINICAL HYPOTHYROIDISM CURRENT CONCEPTS & M ANAGEMENT STRATEGEIES

    Directory of Open Access Journals (Sweden)

    Radha Krishnan

    2015-05-01

    Full Text Available Subclinical hypothyroidism is a biochemical diagnosis characterized by raised thyroid stimulating hormone ( TSH and normal free T3 & T4 , without clinical features of hypothyroidism . Clinical significance of SCH remains uncertain and controversial . Symptoms of SCH may vary from being asymptomatic to having mild nonspecific symptoms . There are still controversies surrounding SCH and associated risk of various cardiovascular diseases ( CVDs , pregnancy outcomes , neuropsychiatric issues , metabolic syndrome , and dyslipidemia . This review will summarize the current data related to the effects of SCH on cardiovascular risk , SCH in pregnancy , in dyslipedemia and clinical guidelines on management of this condition . The evidence has been updated by a Pub med search on the risks and treatment of subclinical hypothyroidism of most recent articles published until March 2015

  9. COMPOSITIONAL AND SUBSTANTIAL STRUCTURE OF THE MEDICAL DOCUMENT: FORMATION STAGES

    Directory of Open Access Journals (Sweden)

    Romashova Olga Vladimirovna

    2015-03-01

    Full Text Available The article deals with the compositional and substantial structure of the ambulatory medical record, or "case history", which has being formed for a long time. The author allocates the three main periods in the formation of this medical document: the first period (the beginning of the 19th century – 1920s is connected with the origin and formation; the second period (1920-1980s is marked by emergence of the normative legal acts regulating registration and maintaining; the third period (1980s – up to the present is associated with the cancellation of regulations and the introduction of the new order of the Ministry of Health of the USSR that changed the document's form and name. It is determined that the composition of the case history consists of the title page and the main part. The following processes take place in the course of ambulatory medical record's formation: strengthening formalization, increase in the number of pattern text fragments, increase in the text's volume, and the implementation of bigger number of functions. The author reveals the main (informative and cumulative, accounting and additional (scientific, controlling, legal, financial functions of the document. The implementation of these functions is reflected in the compositional and substantial structure of the document text and is conditioned by a number of extralinguistic factors.

  10. Identification and assessment of groundwater flow and storage components of the relict Schöneben Rock Glacier, Niedere Tauern Range, Eastern Alps (Austria)

    Science.gov (United States)

    Winkler, Gerfried; Wagner, Thomas; Pauritsch, Marcus; Birk, Steffen; Kellerer-Pirklbauer, Andreas; Benischke, Ralf; Leis, Albrecht; Morawetz, Rainer; Schreilechner, Marcellus G.; Hergarten, Stefan

    2016-06-01

    More than 2,600 relict rock glaciers are known in the Austrian Alps but the knowledge of their hydraulic properties is severely limited. The relict Schöneben Rock Glacier (Niedere Tauern Range, Austria), with an extension of 0.17 km2, was investigated based on spring data (2006-2014) and seismic refraction survey. Spring-discharge hydrographs and natural and artificial tracer data suggest a heterogeneous aquifer with a layered internal structure for the relict rock glacier. The discharge behavior exhibits a fast and a delayed flow component. The spring discharge responds to recharge events within a few hours but a mean residence time of several months can also be observed. The internal structure of the rock glacier (up to several tens of meters thick) consists of: an upper blocky layer with a few meters of thickness, which lacks fine-grained sediments; a main middle layer with coarse and finer-grained sediments, allowing for fast flow; and an approximately 10-m-thick basal till layer as the main aquifer body responsible for the base flow. The base-flow component is controlled by (fine) sandy to silty sediments with low hydraulic conductivity and high storage capacity, exhibiting a difference in hydraulic conductivity to the upper layer of about three orders of magnitude. The high storage capacity of relict rock glaciers has an impact on water resources management in alpine catchments and potentially regulates the risk of natural hazards such as floods and related debris flows. Thus, the results highlight the importance of such aquifer systems in alpine catchments.

  11. Even Cancers Want Commitment: Lineage Identity and Medulloblastoma Formation

    Science.gov (United States)

    Eberhart, Charles G.

    2015-01-01

    In this issue of Cancer Cell, Yang et al. (2008) and Schüller et al. (2008) show that Hedgehog activation in either multipotent neural stem cells or developmentally restricted progenitors causes only medulloblastomas to form. These data suggest that some stem cell-derived tumors must commit to a specific lineage in order to grow. PMID:18691544

  12. 76 FR 78336 - Proposed Collection; Comment Request for Form 1040 and Schedules A, B, C, C-EZ, D, D-1, E, EIC, F...

    Science.gov (United States)

    2011-12-16

    ... when complying with Federal tax laws and incorporates results from a survey of tax year 2007 individual... tax situation of the taxpayer, the type of software or professional preparer used, and the geographic... SCH H X Household Employment Taxes. 1040 SCH J Income Averaging for Farmers and Fishermen. 1040 SCH R...

  13. The Optimal Cut-Off Value of Neutrophil-to-Lymphocyte Ratio for Predicting Prognosis in Adult Patients with Henoch–Schönlein Purpura

    Science.gov (United States)

    Park, Chan Hyuk; Han, Dong Soo; Jeong, Jae Yoon; Eun, Chang Soo; Yoo, Kyo-Sang; Jeon, Yong Cheol; Sohn, Joo Hyun

    2016-01-01

    Background The development of gastrointestinal (GI) bleeding and end-stage renal disease (ESRD) can be a concern in the management of Henoch–Schönlein purpura (HSP). We aimed to evaluate whether the neutrophil-to-lymphocyte ratio (NLR) is associated with the prognosis of adult patients with HSP. Methods Clinical data including the NLR of adult patients with HSP were retrospectively analyzed. Patients were classified into three groups as follows: (a) simple recovery, (b) wax & wane without GI bleeding, and (c) development of GI bleeding. The optimal cut-off value was determined using a receiver operating characteristics curve and the Youden index. Results A total of 66 adult patients were enrolled. The NLR was higher in the GI bleeding group than in the simple recovery or wax & wane group (simple recovery vs. wax & wane vs. GI bleeding; median [IQR], 2.32 [1.61–3.11] vs. 3.18 [2.16–3.71] vs. 7.52 [4.91–10.23], P<0.001). For the purpose of predicting simple recovery, the optimal cut-off value of NLR was 3.18, and the sensitivity and specificity were 74.1% and 75.0%, respectively. For predicting development of GI bleeding, the optimal cut-off value was 3.90 and the sensitivity and specificity were 87.5% and 88.6%, respectively. Conclusions The NLR is useful for predicting development of GI bleeding as well as simple recovery without symptom relapse. Two different cut-off values of NLR, 3.18 for predicting an easy recovery without symptom relapse and 3.90 for predicting GI bleeding can be used in adult patients with HSP. PMID:27073884

  14. Metabolomics analysis reveals elevation of 3-indoxyl sulfate in plasma and brain during chemically-induced acute kidney injury in mice: Investigation of nicotinic acid receptor agonists

    International Nuclear Information System (INIS)

    Zgoda-Pols, Joanna R.; Chowdhury, Swapan; Wirth, Mark; Milburn, Michael V.; Alexander, Danny C.; Alton, Kevin B.

    2011-01-01

    An investigative renal toxicity study using metabolomics was conducted with a potent nicotinic acid receptor (NAR) agonist, SCH 900424. Liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) techniques were used to identify small molecule biomarkers of acute kidney injury (AKI) that could aid in a better mechanistic understanding of SCH 900424-induced AKI in mice. The metabolomics study revealed 3-indoxyl sulfate (3IS) as a more sensitive marker of SCH 900424-induced renal toxicity than creatinine or urea. An LC-MS assay for quantitative determination of 3IS in mouse matrices was also developed. Following treatment with SCH 900424, 3IS levels were markedly increased in murine plasma and brain, thereby potentially contributing to renal- and central nervous system (CNS)-related rapid onset of toxicities. Furthermore, significant decrease in urinary excretion of 3IS in those animals due to compromised renal function may be associated with the elevation of 3IS in plasma and brain. These data suggest that 3IS has a potential to be a marker of renal and CNS toxicities during chemically-induced AKI in mice. In addition, based on the metabolomic analysis other statistically significant plasma markers including p-cresol-sulfate and tryptophan catabolites (kynurenate, kynurenine, 3-indole-lactate) might be of toxicological importance but have not been studied in detail. This comprehensive approach that includes untargeted metabolomic and targeted bioanalytical sample analyses could be used to investigate toxicity of other compounds that pose preclinical or clinical development challenges in a pharmaceutical discovery and development. - Research highlights: → Nicotinic acid receptor agonist, SCH 900424, caused acute kidney injury in mice. → MS-based metabolomics was conducted to identify potential small molecule markers of renal toxicity. → 3-indoxyl-sulfate was found to be as a more sensitive marker of renal toxicity than

  15. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

    Science.gov (United States)

    2015-01-10

    three phases of life were substantially varied between and within regions. For most countries, the general pattern of reductions in age-sex specific mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade. Bill & Melinda Gates Foundation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Predicting Causes of Data Quality Issues in a Clinical Data Research Network.

    Science.gov (United States)

    Khare, Ritu; Ruth, Byron J; Miller, Matthew; Tucker, Joshua; Utidjian, Levon H; Razzaghi, Hanieh; Patibandla, Nandan; Burrows, Evanette K; Bailey, L Charles

    2018-01-01

    Clinical data research networks (CDRNs) invest substantially in identifying and investigating data quality problems. While identification is largely automated, the investigation and resolution are carried out manually at individual institutions. In the PEDSnet CDRN, we found that only approximately 35% of the identified data quality issues are resolvable as they are caused by errors in the extract-transform-load (ETL) code. Nonetheless, with no prior knowledge of issue causes, partner institutions end up spending significant time investigating issues that represent either inherent data characteristics or false alarms. This work investigates whether the causes (ETL, Characteristic, or False alarm) can be predicted before spending time investigating issues. We trained a classifier on the metadata from 10,281 real-world data quality issues, and achieved a cause prediction F1-measure of up to 90%. While initially tested on PEDSnet, the proposed methodology is applicable to other CDRNs facing similar bottlenecks in handling data quality results.

  17. Effects of 18 months of L-T4 replacement in women with subclinical hypothyroidism.

    LENUS (Irish Health Repository)

    Adrees, M

    2012-02-01

    CONTEXT: Some of the cardiovascular and renal abnormalities seen in overt hypothyroidism have also been reported in subclinical hypothyroidism (SCH). Short-term L-T4 replacement in SCH improves cardiovascular risk markers and reduces carotid intima-media thickness (CIMT), a surrogate marker of atherosclerosis. The haemodynamic and renal effects of L-T4 replacement in SCH are poorly understood. OBJECTIVES: To compare cardiovascular risk factors and renal variables in women with SCH and normal women. To study the effects of L-T4 replacement in SCH subjects on these variables and on structural and functional changes in common carotid and brachial arteries. DESIGN: Fifty-six women with SCH before and after L-T4 replacement for 18 months and 56 normal women of similar age distribution were studied. Blood Pressure (BP), plasma lipids and homocysteine were measured and renal function evaluated [estimation of glomerular filtration rate (eGFR) using standard equations and measurement of serum Cystatin-C] in women with SCH before and after 18 months of l-T4, and in healthy women. CIMT and endothelial function (using brachial artery ultrasound) were studied before and after L-T4 in a subgroup of women with SCH. RESULTS: Systolic and diastolic BP, total cholesterol, triglyceride, LDL-cholesterol, lipoprotein(a) and homocysteine were greater in SCH (P < 0.05), and following L-T4 replacement decreased (P < 0.05) to levels that no longer differed from normal subjects. Estimated GFR was reduced and serum Cystatin-C increased (P < 0.05) in SCH. These variables also normalized following L-T4. Following L-T4 replacement the carotid artery baseline diameter increased by 7.1% and CIMT decreased by a mean value of 13%, while brachial artery diameter increased basally by 12.5% and following endothelium-dependent vasodilatation by 17.5% (P < 0.05). However, the increment following reactive hyperaemia did not differ before or following L-T4 replacement. CONCLUSION: Normalization of

  18. Utilization of sediments from dam/jam installation as a rooting capacity for ground layer on agricultural faces; Verwertung von Sedimenten aus Talsperren/Stauanlagen als durchwurzelbare Bodenschicht auf landwirtschaftlichen Flaechen

    Energy Technology Data Exchange (ETDEWEB)

    Baer, Frank

    2011-09-15

    After research to utilization possibilities of the sediments, the by law stipulated duty for the utilization of the sediments after KrW-/AbfG, the basics of the paragraph 12 of the BBodSchV, the cost con-siderations carried out and the intense investigations of the sediments and the place of utilization could be proved, that to turn over the utilization of the sediments to paragraph 17 BBodSchG onto areas of arable land paragraph 12 BBodSchV and with paragraph 17 BBodSchG the ecological and economic favorable variant represents.

  19. 76 FR 32215 - Agency Information Collection Activities; Proposed Collection; Comment Request; Substantiation...

    Science.gov (United States)

    2011-06-03

    ... of such disease in the United States [(U.S.)], describes the role of a nutrient or dietary ingredient... substantiation for their claims in the scientific literature. The time it takes to assemble the necessary... based on emerging science, where conducting literature searches and understanding the literature takes...

  20. Protective effect of caffeine and a selective A2A receptor antagonist on impairment of memory and oxidative stress of aged rats.

    Science.gov (United States)

    Leite, Marlon Régis; Wilhelm, Ethel A; Jesse, Cristiano R; Brandão, Ricardo; Nogueira, Cristina Wayne

    2011-04-01

    In this study, the effects of caffeine (CAF) and SCH58261, a selective A(2A) receptor antagonist, on memory impairment and oxidative stress generated by aging in rats were investigated. Young and aged rats were treated daily per 10 days with CAF (30 mg/kg p.o.) or SCH58261 (0.5mg/kg, p.o.) or vehicle (1 ml/kg p.o.). Rats were trained and tested in a novel object recognition task. After the behavioral test, ascorbic acid and oxygen and nitrogen reactive species levels as well as Na(+)K(+) ATPase activity were determined in rat brain. The results demonstrated that the age-related memory deficit was reversed by treatment with CAF or SCH58261. Treatment with CAF or SCH58261 significantly normalized oxygen and nitrogen reactive species levels increased in brains of aged rats. Na(+)K(+) ATPase activity inhibited in brains of aged rats was also normalized by CAF or SCH58261 treatment. A decrease in basal ascorbic acid levels in brains of aged rats was not changed by CAF or SCH58261. These results demonstrated that CAF and SCH58261, modulators of adenosinergic receptors, were able to reverse age-associated memory impairment and to partially reduce oxidative stress. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. Death rates for acquired hypothyroidism and thyrotoxicosis in English populations (1979-2010): comparison of underlying cause and all certified causes.

    Science.gov (United States)

    Goldacre, M J; Duncan, M E

    2013-03-01

    Overt hypothyroidism and thyrotoxicosis have widespread systemic effects and are associated with increased mortality. Most death certificates that include them do not have the thyroid disease coded as the underlying cause of death. To describe regional (1979-2010) and national (1995-2010) trends in mortality rates for acquired hypothyroidism and thyrotoxicosis, analysing all certified causes of death (termed 'mentions') and not just the underlying cause. Analysis of death registration data. Analysis of data for the Oxford region (mentions available from 1979) and English national data (mentions available from 1995). The data were grouped in periods defined by different national rules for selecting the underlying cause of death (1979-83, 1984-92, 1993-2000 and 2001-10) and were also analysed as single calendar years. Mentions mortality for acquired hypothyroidism in the Oxford region declined significantly from 1979 to 2010: the average annual percentage change (AAPC) was -2.6% (95% confidence intervals -3.5, -1.8). Most of the decrease occurred during the 1980s. The AAPC in rates for later years in England (1995-2010) was non-significant at 0.2% (-0.7, 1.0). Mortality rates for thyrotoxicosis decreased significantly: the AAPC was -2.8% (-4.1, -1.5) in the Oxford region and -3.8% (-4.7, -3.0) in England. In England, between 2001 and 2010, hypothyroidism or thyrotoxicosis was coded as the underlying cause of death on, respectively, 17 and 24% of death certificates that included them. Mortality rates for hypothyroidism and thyrotoxicosis have fallen substantially. The fall is probably wholly or mainly a result of improved care.

  2. Subclinical hypothyroidism is associated with higher carotid intima-media thickness in cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

    Science.gov (United States)

    Peixoto de Miranda, É J F; Bittencourt, M S; Pereira, A C; Goulart, A C; Santos, I S; Lotufo, P A; Bensenor, I M

    2016-10-01

    Although subclinical hypothyroidism (SCH) is associated with cardiovascular risk, there is scarce data about subclinical atherosclerosis in subjects with SCH. We aimed to analyze the association between SCH and carotid intima-media thickness (IMT) using baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We included subjects with normal thyroid function (TSH: 0.4-4.0 mIU/l, and normal free thyroxine (FT4): 0.8-1.9 ng/dl) and SCH (TSH ≥ 4.0 mIU/l and normal FT4) evaluated for IMT in a cross-sectional analysis. We excluded individuals using medications that affect thyroid function and those with a history of cardiovascular disease. We performed logistic and linear regression models to evaluate the association with IMT (mean values and categorized at the 75th percentile) as a dependent variable and SCH as an independent variable, adjusted for other cardiovascular risk factors. From 8623 subjects (median age of 50 years; interquartile range: 44-57), 4624 (53.6%) were women, 8095 (93.9%) were euthyroid, and 528 (6.1%) had SCH. Groups varied in age, body mass index, Framingham risk score, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), C-reactive protein, as well as, IMT, that were all higher in SCH compared to euthyroid participants. SCH is associated with IMT as a continuous variable (β = 0.010, P = 0.036) and IMT >75th percentile: OR = 1.30 (95% CI = 1.06-1.59) in logistic models. Individuals with SCH presented higher IMT compared with euthyroid subjects, even after adjustment for potential confounders. IMT was independently associated with SCH in the baseline of the ELSA-Brasil study. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  3. Exploring non-stationarity patterns in schizophrenia: neural reorganization abnormalities in the alpha band

    Science.gov (United States)

    Núñez, Pablo; Poza, Jesús; Bachiller, Alejandro; Gomez-Pilar, Javier; Lubeiro, Alba; Molina, Vicente; Hornero, Roberto

    2017-08-01

    Objective. The aim of this paper was to characterize brain non-stationarity during an auditory oddball task in schizophrenia (SCH). The level of non-stationarity was measured in the baseline and response windows of relevant tones in SCH patients and healthy controls. Approach. Event-related potentials were recorded from 28 SCH patients and 51 controls. Non-stationarity was estimated in the conventional electroencephalography frequency bands by means of Kullback-Leibler divergence (KLD). Relative power (RP) was also computed to assess a possible complementarity with KLD. Main results. Results showed a widespread statistically significant increase in the level of non-stationarity from baseline to response in all frequency bands for both groups. Statistically significant differences in non-stationarity were found between SCH patients and controls in beta-2 and in the alpha band. SCH patients showed more non-stationarity in the left parieto-occipital region during the baseline window in the beta-2 band. A leave-one-out cross validation classification study with feature selection based on binary stepwise logistic regression to discriminate between SCH patients and controls provided a positive predictive value of 72.73% and negative predictive value of 78.95%. Significance. KLD can characterize transient neural reorganization during an attentional task in response to novelty and relevance. Our findings suggest anomalous reorganization of neural dynamics in SCH during an oddball task. The abnormal frequency-dependent modulation found in SCH patients during relevant tones is in agreement with the hypothesis of aberrant salience detection in SCH. The increase in non-stationarity in the alpha band during the active task supports the notion that this band is involved in top-down processing. The baseline differences in the beta-2 band suggest that hyperactivation of the default mode network during attention tasks may be related to SCH symptoms. Furthermore, the classification

  4. Notes on Michael Schülke's pselaphine collections from China. - Tyrini. I. genera Labomimus Sharp, Linan Hlaváč and Pselaphodes Westwood (Coleoptera, Staphylinidae, Pselaphinae).

    Science.gov (United States)

    Yin, Zi-Wei; Li, Li-Zhen

    2012-01-01

    This paper is the first of a series that deals with Dr. Michael Schülke's collection of Pselaphinae from China. The tyrine genera Labomimus Sharp, Linan Hlaváč and Pselaphodes Westwood are chosen for the first part. The study revealed fourteen new species, all described and illustrated: Labomimus cognatus Yin & Li, sp. n. (Yunnan), Labomimus dabashanus Yin & Li, sp. n. (Hubei, Shaanxi), Labomimus mirus Yin & Li, sp. n. (Yunnan), Labomimus paratorus Yin & Li, sp. n. (Shaanxi), Labomimus sarculus Yin & Li, sp. n. (Yunnan), Labomimus schuelkei Yin & Li, sp. n. (Shaanxi), Labomimus vespertilio Yin & Li, sp. n. (Yunnan), Linan tendothorax Yin & Li, sp. n. (Yunnan), Pselaphodes distincticornis Yin & Li, sp. n. (Yunnan), Pselaphodes erlangshanus Yin & Li, sp. n. (Sichuan), Pselaphodes flexus Yin & Li, sp. n. (Yunnan), Pselaphodes tibialis Yin & Li, sp. n. (Yunnan), Pselaphodes venustus Yin & Li, sp. n. (Yunnan) and Pselaphodes zhongdianus Yin & Li, sp. n. (Yunnan). Pselaphodes jizushanus Yin, Li & Zhao is recorded from a new locality in Yunnan and its aedeagus is newly illustrated; new province records for Pselaphodes nomurai Yin, Li & Zhao is provided. Labomimus torus (Yin, Li & Zhao), comb. n. is moved from Pselaphodes after an examination of the holotype. Species represented only by unassociated females are listed with label data.

  5. 21 CFR 101.43 - Substantial compliance of food retailers with the guidelines for the voluntary nutrition labeling...

    Science.gov (United States)

    2010-04-01

    ... FOR HUMAN CONSUMPTION FOOD LABELING Specific Nutrition Labeling Requirements and Guidelines § 101.43 Substantial compliance of food retailers with the guidelines for the voluntary nutrition labeling of raw fruit... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Substantial compliance of food retailers with the...

  6. Substantial injuries influence ranking position in young elite athletes of athletics, cross-country skiing and orienteering.

    Science.gov (United States)

    von Rosen, P; Heijne, A

    2018-04-01

    The relationship between injury and performance in young athletes is scarcely studied. The aim of this study was therefore to explore the association between injury prevalence and ranking position among adolescent elite athletes. One hundred and sixty-two male and female adolescent elite athletes (age range 15-19), competing in athletics (n = 59), cross-country skiing (n = 66), and orienteering (n = 37), were monitored weekly over 22-47 weeks using a web-based injury questionnaire. Ranking lists were collected. A significant (P = .003) difference was found in the seasonal substantial injury prevalence across the ranked athletes over the season, where the top-ranked (median 3.6%, 25-75th percentiles 0%-14.3%) and middle-ranked athletes (median 2.3%, 25-75th percentiles 0%-10.0%) had a lower substantial injury prevalence compared to the low-ranked athletes (median 11.3%, 25-75th percentiles 2.5%-27.1%), during both preseason (P = .002) and competitive season (P = .031). Athletes who improved their ranking position (51%, n = 51) reported a lower substantial injury prevalence (median 0%, 25-75th percentiles 0%-10.0%) compared to those who decreased (49%, n = 49) their ranking position (md 6.7%, 25-75th percentiles 0%-22.5%). In the top-ranked group, no athlete reported substantial injury more than 40% of all data collection time points compared to 9.6% (n = 5) in the middle-ranked, and 17.3% (n = 9) in the low-ranked group. Our results provide supporting evidence that substantial injuries, such as acute and overuse injuries leading to moderate or severe reductions in training or sports performance, influence ranking position in adolescent elite athletes. The findings are crucial to stakeholders involved in adolescent elite sports and support the value of designing effective preventive interventions for substantial injuries. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. 49 CFR Schedule D to Subpart B of... - Schedule D to Subpart B of Part 1139

    Science.gov (United States)

    2010-10-01

    ... Miscellaneous and financial ratios: 29Cash dividend appropriations Sch. 2930, L. 16 30Operating ratio (percent... Lines, Inc. and all the study carrier carriers by an analysis of certain key financial data, with a view... financial data Income statement data: 1Total revenues Sch. 2998, L. 9 2Total expenses Sch. 2998, L. 15...

  8. Neighborhood-level social processes and substantiated cases of child maltreatment.

    Science.gov (United States)

    Molnar, Beth E; Goerge, Robert M; Gilsanz, Paola; Hill, Andrea; Subramanian, S V; Holton, John K; Duncan, Dustin T; Beatriz, Elizabeth D; Beardslee, William R

    2016-01-01

    Child maltreatment is a preventable public health problem. Research has demonstrated that neighborhood structural factors (e.g. poverty, crime) can influence the proportion of a neighborhood's children who are victims of maltreatment. A newer strategy is the identification of potentially modifiable social processes at the neighborhood level that can also influence maltreatment. Toward this end, this study examines neighborhood-level data (maltreatment cases substantiated by Illinois' child protection agency, 1995-2005, social processes measured by the Project on Human Development in Chicago Neighborhoods, U.S. Census data, proportions of neighborhoods on public assistance, and crime data) that were linked across clusters of contiguous, relatively homogenous Chicago, IL census tracts with respect to racial/ethnic and socioeconomic composition. Our analysis-an ecological-level, repeated cross-sectional design utilizing random-intercept logit models-with a sensitivity analysis using spatial models to control for spatial autocorrelation-revealed consistent associations between neighborhood social processes and maltreatment. Neighborhoods higher in collective efficacy, intergenerational closure, and social networks, and lower in disorder had lower proportions of neglect, physical abuse, and sexual abuse substantiated cases, controlling for differences in structural factors. Higher collective efficacy and social network size also predicted a lower proportion of substance-exposed infants. This research indicates that strategies to mobilize neighborhood-level protective factors may decrease child maltreatment more effectively than individual and family-focused efforts alone. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Substantial Churn In Health Insurance Offerings By Small Employers, 2014-15.

    Science.gov (United States)

    Vistnes, Jessica P; Rohde, Frederick; Miller, G Edward; Cooper, Philip F

    2017-09-01

    New data for 2014-15 from the Medical Expenditure Panel Survey-Insurance Component longitudinal survey show substantial churn in insurance offers by small employers (those with fifty or fewer workers), with 14.6 percent of employers that offered insurance in 2014 having dropped it in 2015 and 5.5 percent of those that did not offer it adding coverage. Project HOPE—The People-to-People Health Foundation, Inc.

  10. SUBCLINICAL HYPOTHYROIDISM CURRENT CONCEPTS & M ANAGEMENT STRATEGEIES

    OpenAIRE

    Radha Krishnan; Soumini; Adithya

    2015-01-01

    Subclinical hypothyroidism is a biochemical diagnosis characterized by raised thyroid stimulating hormone ( TSH ) and normal free T3 & T4 , without clinical features of hypothyroidism . Clinical significance of SCH remains uncertain and controversial . Symptoms of SCH may vary from being asymptomatic to having mild nonspecific symptoms . There are still controversies surrounding SCH and associated risk of ...

  11. Apatite Fission-Track Analysis of the Middle Jurassic Todos Santos Formation from Chiapas, Mexico.

    Science.gov (United States)

    Abdullin, Fanis; Solé, Jesús; Shchepetilnikova, Valentina; Solari, Luigi; Ortega-Obregón, Carlos

    2014-05-01

    The Sierra de Chiapas (SCH), located in the south of Mexico, is a complex geological province that can be divided on four different lithological or tectonic areas: (1) the Chiapas Massif Complex (CMC); (2) the Central Depression; (3) the Strike-slip Fault Province, and (4) the Chiapas Fold-and-thrust Belt. The CMC mostly consists of Permian granitoids and meta-granitoids, and represents the basement of the SCH. During the Jurassic period red beds and salt were deposited on this territory, related to the main pulse of rifting and opening of the Gulf of Mexico. Most of the Cretaceous stratigraphy contains limestones and dolomites deposited on a marine platform setting during the postrift stage of the Gulf of Mexico rift. During the Cenozoic Era took place the major clastic sedimentation along the SCH. According the published low-temperature geochronology data (Witt et al., 2012), SCH has three main phases of thermo-tectonic history: (1) slow exhumation between 35 and 25 Ma, that affected mainly the basement (CMC) and is probably related to the migration of the Chortís block; (2) fast exhumation during the Middle-Late Miocene caused by strike-slip deformation that affects almost all Chiapas territory; (3) period of rapid cooling from 6 to 5 Ma, that affects the Chiapas Fold-and-thrust Belt, coincident with the landward migration of the Caribbean-North America plate boundaries. The two last events were the most significant on the formation of the present-day topography of the SCH. However, the stratigraphy of the SCH shows traces of the existence of earlier tectonic events. This study presents preliminary results of apatite fission-track (AFT) dating of sandstones from the Todos Santos Formation (Middle Jurassic). The analyses are performed with in situ uranium determination using LA-ICP-MS (e.g., Hasebe et al., 2004). The AFT data indicate that this Formation has suffered high-grade diagenesis (probably over 150 ºC) and the obtained cooling ages, about 70-60 Ma

  12. Algorithms for enhancing public health utility of national causes-of-death data

    Directory of Open Access Journals (Sweden)

    Pourmalek Farshad

    2010-05-01

    Full Text Available Abstract Background Coverage and quality of cause-of-death (CoD data varies across countries and time. Valid, reliable, and comparable assessments of trends in causes of death from even the best systems are limited by three problems: a changes in the International Statistical Classification of Diseases and Related Health Problems (ICD over time; b the use of tabulation lists where substantial detail on causes of death is lost; and c many deaths assigned to causes that cannot or should not be considered underlying causes of death, often called garbage codes (GCs. The Global Burden of Disease Study and the World Health Organization have developed various methods to enhance comparability of CoD data. In this study, we attempt to build on these approaches to enhance the utility of national cause-of-death data for public health analysis. Methods Based on careful consideration of 4,434 country-years of CoD data from 145 countries from 1901 to 2008, encompassing 743 million deaths in ICD versions 1 to 10 as well as country-specific cause lists, we have developed a public health-oriented cause-of-death list. These 56 causes are organized hierarchically and encompass all deaths. Each cause has been mapped from ICD-6 to ICD-10 and, where possible, they have also been mapped to the International List of Causes of Death 1-5. We developed a typology of different classes of GCs. In each ICD revision, GCs have been identified. Target causes to which these GCs should be redistributed have been identified based on certification practice and/or pathophysiology. Proportionate redistribution, statistical models, and expert algorithms have been developed to redistribute GCs to target codes for each age-sex group. Results The fraction of all deaths assigned to GCs varies tremendously across countries and revisions of the ICD. In general, across all country-years of data available, GCs have declined from more than 43% in ICD-7 to 24% in ICD-10. In some regions, such

  13. Scientific Opinion on the substantiation of a health claim related to Bifidobacterium bifidum CNCM I-3426 and defence against pathogens in the upper respiratory tract pursuant to Article 13(5) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    2015-01-01

    Following an application from Lallemand Health Solutions, submitted pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of France, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation...... effect. The Panel considers that no conclusions can be drawn from either of the human studies for the scientific substantiation of the claim. In the absence of evidence of an effect of B. bifidum CNCM I3426 on defence against pathogens in the upper respiratory tract in humans, the results of the in vitro...... study submitted cannot be used as a source of data for the scientific substantiation of the claim. The Panel concludes that a cause and effect relationship has not been established between the consumption of B. bifidum CNCM I-3426 and defence against pathogens in the upper respiratory tract....

  14. Dichtung als Blüte der Wahrheit Fiction as Blossom of Truth

    Directory of Open Access Journals (Sweden)

    Susanne Gramatzki

    2006-03-01

    Full Text Available Kaum eine andere Schriftstellerin hat so konsequent – man ist versucht, zu sagen: so ernsthaft – mit fremden Identitäten gespielt wie Else Lasker-Schüler, die sich selbst als Tino von Bagdad oder Prinz Jussuf von Theben imaginierte und ihren Freunden erfindungsreiche Namen beilegte. Realität und Phantasie flossen in ihrem Leben und Werk stets zusammen. Sigrid Bauschinger, ehemalige Professorin an der University of Massachusetts und bereits 1980 mit einer umfangreichen Studie über Else Lasker-Schüler hervorgetreten (Else Lasker-Schüler. Ihr Werk und ihre Zeit, hat es nun unternommen, auf Grundlage bisher unveröffentlicher Dokumente eine neue Biographie der bedeutenden Wuppertaler Autorin zu verfassen.Almost no other female author has played with foreign identities as consistently—one could almost say as seriously—as Else Lasker-Schüler, who fashioned herself as Tino von Baghdad or Prince Jussuf von Theben and affixed her friends with imaginative names. Reality and fantasy were intertwined in her life and work. Sigrid Bauschinger, formerly professor at the University of Massachusetts, already presented a comprehensive study of Else Lasker-Schüler in 1980 (Else Lasker-Schüler. Ihr Werk und ihre Zeit/Else Lasker-Schüler. Her Work and Her Time. She has now written a new biography of the Wuppertal author based on previously unpublished documents.

  15. Subchorionic hematomas are increased in early pregnancy in women taking low-dose aspirin.

    Science.gov (United States)

    Truong, Ashley; Sayago, M Mercedes; Kutteh, William H; Ke, Raymond W

    2016-05-01

    To determine the frequency of subchorionic hematomas (SCH) in first-trimester ultrasound examinations of patients with infertility and recurrent pregnancy loss (RPL) and in patients from a general obstetric population. To determine if the method of assisted reproduction utilized or the use of anticoagulants, such as heparin and aspirin (ASA), influenced frequency of SCH. Prospective, cohort study. Fertility clinic and general obstetrics clinic. Five hundred and thirty-three women who were pregnant in the first-trimester. Not applicable. Frequencies of subchorionic hematomas in women based on diagnosis, use of anticoagulants, and fertility treatment. SCH were identified in 129/321 (40.2%) in the study group compared to 23/212 (10.9%) in the control group. Fertility diagnosis and the use of heparin did not appear to affect the frequency of SCH in the first trimester; however, SCH occurred at an almost four-fold increase in patients taking ASA compared to those not taking ASA, regardless of fertility diagnosis or method of fertility treatment. The use of ASA may be associated with an increased risk of developing a SCH during the first trimester. The increased frequencies of SCH in pregnancies of patients attending a fertility clinic compared to women from a general obstetrical practice was highly correlated with the use of ASA. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  16. Total thyroidectomy: a clue to understanding the metabolic changes induced by subclinical hyperthyroidism?

    Science.gov (United States)

    Bel Lassen, Pierre; Kyrilli, Aglaia; Lytrivi, Maria; Ruiz Patino, Maria; Corvilain, Bernard

    2017-02-01

    The effects of endogenous subclinical hyperthyroidism (eSCH) on heart and bone have been well documented. There are only limited data available regarding the impact of eSCH on weight regulation and lipid metabolism. Our aim was to evaluate the changes in body weight and metabolic parameters after total thyroidectomy in patients with pre-operative eSCH compared with pre-operative patients with euthyroid (EUT). A retrospective study of 505 patients who underwent total thyroidectomy for benign multinodular goitre in an academic hospital in Brussels (Belgium) was performed. Two hundred and 25 patients were included (eSCH group: n = 74; EUT group: n = 151). The mean follow-up time was 26·1 ± 0·8 months and was similar in both groups. Absolute BMI gain was significantly greater in the eSCH group than in the EUT group (1·11 ± 0·17 vs 0·33 ± 0·13 kg/m 2 ; P = 0·003). A significant increase in LDL cholesterol was observed in the eSCH group (16·1 ± 3·8 mg/dl; P effect of eSCH on body weight regulation and lipid metabolism. © 2016 John Wiley & Sons Ltd.

  17. Iatrogenic Subclinical Hyperthyroidism Does Not Promote Weight Loss.

    Science.gov (United States)

    Kedia, Rohit; Lowes, Alicia; Gillis, Sarah; Markert, Ronald; Koroscil, Thomas

    2016-02-01

    Among patients who have undergone total thyroidectomy, do those with thyroid cancer being kept iatrogenically subclinical hyperthyroid (SCH) differ from euthyroid patients in long-term weight change? In a retrospective study, medical records identified 291 patients who had undergone a thyroidectomy for differentiated thyroid cancer or benign thyroid disease. Weight, thyroid-stimulating hormone, and levothyroxine dose were measured presurgery and 1, 2, and 3 years postsurgery. Of 291 patients, 147 were in the SCH group and 144 were in the euthyroid group. At all 3 years both groups gained weight from baseline, but the two groups did not differ in weight change from baseline at any time period: year 1 (SCH mean 0.4% ± 6.2% weight gain vs euthyroid group mean 2.2% ± 6.6% weight gain; P = 0.12), year 2 (SCH mean 1.1% ± 9.1% weight gain vs euthyroid mean 2.9% ± 7.8% weight gain; P = 0.22), and year 3 (SCH mean 2.6% ± 9.2% weight gain vs euthyroid mean 3.1% ± 11.1% weight gain; P = 0.49). Among total thyroidectomy patients, weight change did not differ between SCH patients and euthyroid patients at years 1 through 3. As such, the use of levothyroxine to induce SCH did not lead to long-term weight change when compared with euthyroid patients.

  18. Oxytocin induces penile erection and yawning when injected into the bed nucleus of the stria terminalis: Involvement of glutamic acid, dopamine, and nitric oxide.

    Science.gov (United States)

    Sanna, Fabrizio; Bratzu, Jessica; Argiolas, Antonio; Melis, Maria Rosaria

    2017-11-01

    Oxytocin (5-100ng), but not Arg 8 -vasopressin (100ng), injected unilaterally into the bed nucleus of the stria terminalis (BNST) induces penile erection and yawning in a dose-dependent manner in male rats. The minimal effective dose was 20ng for penile erection and 5ng for yawning. Oxytocin responses were abolished not only by the oxytocin receptor antagonist d(CH 2 ) 5 Tyr(Me) 2 -Orn 8 -vasotocin (1μg), but also by (+) MK-801 (1μg), an excitatory amino acid receptor antagonist of the N-methyl-d-aspartic acid (NMDA) subtype, SCH 23390 (1μg), a D1 receptor antagonist, but not haloperidol (1μg), a D2 receptor antagonist, and SMTC (40μg), an inhibitor of neuronal nitric oxide synthase, injected into the BNST 15min before oxytocin. Oxytocin-induced penile erection, but not yawning, was also abolished by CNQX (1μg), an excitatory amino acid receptor antagonist of the AMPA subtype. In contrast, oxytocin responses were not reduced by bicuculline (20ng), a GABA A receptor antagonist, phaclofen (5μg), a GABA B receptor antagonist, CP 376395, a CRF receptor-1 antagonist (5μg), or astressin 2B, a CRF receptor-2 antagonist (150ng). Considering the ability of NMDA (100ng) to induce penile erection and yawning when injected into the BNST and the available evidence showing possible interaction among oxytocin, glutamic acid, and dopamine in the BNST, oxytocin possibly activates glutamatergic neurotransmission in the BNST. This in turn leads to the activation of neural pathways projecting back to the paraventricular nucleus, medial preoptic area, ventral tegmental area, and/or ventral subiculum/amygdala, thereby inducing penile erection and yawning. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Striatal dopamine D1 and D2 receptors: widespread influences on methamphetamine-induced dopamine and serotonin neurotoxicity.

    Science.gov (United States)

    Gross, Noah B; Duncker, Patrick C; Marshall, John F

    2011-11-01

    Methamphetamine (mAMPH) is an addictive psychostimulant drug that releases monoamines through nonexocytotic mechanisms. In animals, binge mAMPH dosing regimens deplete markers for monoamine nerve terminals, for example, dopamine and serotonin transporters (DAT and SERT), in striatum and cerebral cortex. Although the precise mechanism of mAMPH-induced damage to monoaminergic nerve terminals is uncertain, both dopamine D1 and D2 receptors are known to be important. Systemic administration of dopamine D1 or D2 receptor antagonists to rodents prevents mAMPH-induced damage to striatal dopamine nerve terminals. Because these studies employed systemic antagonist administration, the specific brain regions involved remain to be elucidated. The present study examined the contribution of dopamine D1 and D2 receptors in striatum to mAMPH-induced DAT and SERT neurotoxicities. In this experiment, either the dopamine D1 antagonist, SCH23390, or the dopamine D2 receptor antagonist, sulpiride, was intrastriatally infused during a binge mAMPH regimen. Striatal DAT and cortical, hippocampal, and amygdalar SERT were assessed as markers of mAMPH-induced neurotoxicity 1 week following binge mAMPH administration. Blockade of striatal dopamine D1 or D2 receptors during an otherwise neurotoxic binge mAMPH regimen produced widespread protection against mAMPH-induced striatal DAT loss and cortical, hippocampal, and amygdalar SERT loss. This study demonstrates that (1) dopamine D1 and D2 receptors in striatum, like nigral D1 receptors, are needed for mAMPH-induced striatal DAT reductions, (2) these same receptors are needed for mAMPH-induced SERT loss, and (3) these widespread influences of striatal dopamine receptor antagonists are likely attributable to circuits connecting basal ganglia to thalamus and cortex. Copyright © 2011 Wiley-Liss, Inc.

  20. Blonanserin Ameliorates Phencyclidine-Induced Visual-Recognition Memory Deficits: the Complex Mechanism of Blonanserin Action Involving D3-5-HT2A and D1-NMDA Receptors in the mPFC

    Science.gov (United States)

    Hida, Hirotake; Mouri, Akihiro; Mori, Kentaro; Matsumoto, Yurie; Seki, Takeshi; Taniguchi, Masayuki; Yamada, Kiyofumi; Iwamoto, Kunihiro; Ozaki, Norio; Nabeshima, Toshitaka; Noda, Yukihiro

    2015-01-01

    Blonanserin differs from currently used serotonin 5-HT2A/dopamine-D2 receptor antagonists in that it exhibits higher affinity for dopamine-D2/3 receptors than for serotonin 5-HT2A receptors. We investigated the involvement of dopamine-D3 receptors in the effects of blonanserin on cognitive impairment in an animal model of schizophrenia. We also sought to elucidate the molecular mechanism underlying this involvement. Blonanserin, as well as olanzapine, significantly ameliorated phencyclidine (PCP)-induced impairment of visual-recognition memory, as demonstrated by the novel-object recognition test (NORT) and increased extracellular dopamine levels in the medial prefrontal cortex (mPFC). With blonanserin, both of these effects were antagonized by DOI (a serotonin 5-HT2A receptor agonist) and 7-OH-DPAT (a dopamine-D3 receptor agonist), whereas the effects of olanzapine were antagonized by DOI but not by 7-OH-DPAT. The ameliorating effect was also antagonized by SCH23390 (a dopamine-D1 receptor antagonist) and H-89 (a protein kinase A (PKA) inhibitor). Blonanserin significantly remediated the decrease in phosphorylation levels of PKA at Thr197 and of NR1 (an essential subunit of N-methyl-D-aspartate (NMDA) receptors) at Ser897 by PKA in the mPFC after a NORT training session in the PCP-administered mice. There were no differences in the levels of NR1 phosphorylated at Ser896 by PKC in any group. These results suggest that the ameliorating effect of blonanserin on PCP-induced cognitive impairment is associated with indirect functional stimulation of the dopamine-D1-PKA-NMDA receptor pathway following augmentation of dopaminergic neurotransmission due to inhibition of both dopamine-D3 and serotonin 5-HT2A receptors in the mPFC. PMID:25120077

  1. Expression of dopamine receptors in the subthalamic nucleus of the rat: characterization using reverse transcriptase-polymerase chain reaction and autoradiography

    International Nuclear Information System (INIS)

    Flores, G.; Liang, J.J.; Sierra, A.; Martinez-Fong, D.; Quirion, R.; Aceves, J.; Srivastava, L.K.

    1999-01-01

    We analysed the expression of dopamine receptor subtypes in the subthalamic nucleus by means of reverse transcriptase-polymerase chain reaction. We also studied, using autoradiography, all pharmacologically characterized dopamine receptors in four subregions of the subthalamic nucleus. For comparison, dopamine receptor subtypes were also evaluated in brain regions where they are more abundant and well characterized. The radioligands used were: [ 3 H]SCH-23390, [ 3 H]emonapride and [ 3 H]2-dipropylamino-7-hydroxy-1,2,3,4-tetrahydronaphthalene for dopamine D 1 , D 2 and D 3 receptors, respectively; and [ 3 H]YM-09151-2 in the presence of raclopride for dopamine D 4 receptors. Finally, we also evaluated the effect of unilateral 6-hydroxydopamine injection into the medial forebrain bundle on dopamine receptor levels expressed in the ipsilateral subthalamic nucleus. The lesion was estimated by decrease in the binding of [ 3 H]WIN-35428, a specific dopamine transporter label. D 1 , D 2 and D 3 receptor messenger RNAs and binding sites were present in the subthalamic nucleus, but no messenger RNA for D 4 receptors was found, although specific binding sites for these receptors were observed. As compared to the intact side, the 6-hydroxydopamine lesion did not change D 1 receptors, increased D 2 receptors, and decreased D 3 receptors and the dopamine transporter. The results suggest that postsynaptic D 1 , D 2 or D 3 receptors can mediate the effect of dopamine on subthalamic nucleus neuronal activity. D 4 receptors would mediate exclusively presynaptic effects.These results reinforce the idea that dopamine receptors in the subthalamic nucleus may play an important role in the physiology of the basal ganglia and in the pathophysiology of Parkinson's disease. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  2. Radiopharmaceuticals in positron emission tomography: Radioisotope productions and radiolabelling procedures at the Austin and Repatriation Medical Centre

    Energy Technology Data Exchange (ETDEWEB)

    Tochon-Danguy, H.J.; Sachinidis, J.I.; Chan, J.G.; Cook, M. [Austin and Repatriation Medical Centre, Melbourne, VIC (Australia). Centre for Positron Emission Tomography

    1997-10-01

    Positron Emission Tomography (PET) is a technique that utilizes positron-emitting radiopharmaceuticals to map the physiology, biochemistry and pharmacology of the human body. Positron-emitting radioisotopes produced in a medical cyclotron are incorporated into compounds that are biologically active in the body. A scanner measures radioactivity emitted from a patient`s body and provides cross-sectional images of the distribution of these radiolabelled compounds in the body. It is the purpose of this paper to review the variety of PET radiopharmaceuticals currently produced at the Austin and Repatriation Medical Centre in Melbourne. Radioisotope production, radiolabelling of molecules and quality control of radiopharmaceuticals will be discussed. A few examples of their clinical applications will be shown as well. During the last five years we achieved a reliable routine production of various radiopharmaceuticals labelled with the four most important positron-emitters: oxygen-15 (t,{sub 1/2}=2min), nitrogen-13 (t{sub 1/2}= 10 min), carbon-11 (t{sub 1/2}=20 min) and fluorine-18 (t{sub 1/2}= 110 min). These radiopharmaceuticals include [{sup 15}O]oxygen, [{sup 15}O]carbon monoxide, [{sup 15}O]carbon dioxide, [{sup 15}O]water, [{sup 13}N]ammonia, [{sup 11}C]flumazenil, [{sup 11}C]SCH23390, [{sup 18}F]fluoromisonidazole and [{sup 18}F]fluoro-deoxy-glucose ([{sup 18}F]FDG). In addition, since the half life of [{sup 18}F] is almost two hours, regional distribution can be done, and the Austin and Repatriation Medical Centre is currently supplying [{sup 18}F]FDG in routine to other hospitals. Future new radiopharmaceuticals development include a [{sup 18}F]thymidine analog to measure cell proliferation and a [{sup 11}C]pyrroloisoquinoline to visualize serotonergic neuron abnormalities. (authors) 23 refs., 2 tabs.

  3. Acute Cocaine Induces Fast Activation of D1 Receptor and Progressive Deactivation of D2 Receptor Strial Neurons: In Vivo Optical Microprobe [Ca2+]i Imaging

    International Nuclear Information System (INIS)

    Du, C.; Luo, Z.; Volkow, N.D.; Heintz, N.; Pan, Y.; Du, C.

    2011-01-01

    Cocaine induces fast dopamine increases in brain striatal regions, which are recognized to underlie its rewarding effects. Both dopamine D1 and D2 receptors are involved in cocaine's reward but the dynamic downstream consequences of cocaine effects in striatum are not fully understood. Here we used transgenic mice expressing EGFP under the control of either the D1 receptor (D1R) or the D2 receptor (D2R) gene and microprobe optical imaging to assess the dynamic changes in intracellular calcium ([Ca 2+ ] i ) responses (used as marker of neuronal activation) to acute cocaine in vivo separately for D1R- versus D2R-expressing neurons in striatum. Acute cocaine (8 mg/kg, i.p.) rapidly increased [Ca 2+ ] i in D1R-expressing neurons (10.6 ± 3.2%) in striatum within 8.3 ± 2.3 min after cocaine administration after which the increases plateaued; these fast [Ca 2+ ] i increases were blocked by pretreatment with a D1R antagonist (SCH23390). In contrast, cocaine induced progressive decreases in [Ca 2+ ] i in D2R-expressing neurons (10.4 ± 5.8%) continuously throughout the 30 min that followed cocaine administration; these slower [Ca 2+ ] i decreases were blocked by pretreatment with a D2R antagonist (raclopride). Since activation of striatal D1R-expressing neurons (direct-pathway) enhances cocaine reward, whereas activation of D2R expressing neurons suppresses it (indirect-pathway) (Lobo et al., 2010), this suggests that cocaine's rewarding effects entail both its fast stimulation ofD1R (resulting in abrupt activation of direct-pathway neurons) and a slower stimulation of D2R (resulting in longer-lasting deactivation of indirect-pathway neurons). We also provide direct in vivo evidence of D2R and D1R interactions in the striatal responses to acute cocaine administration.

  4. Modulation of risk/reward decision making by dopaminergic transmission within the basolateral amygdala.

    Science.gov (United States)

    Larkin, Joshua D; Jenni, Nicole L; Floresco, Stan B

    2016-01-01

    Dopamine (DA) transmission within cortico-limbic-striatal circuitry is integral in modulating decisions involving reward uncertainty. The basolateral amygdala (BLA) also plays a role in these processes, yet how DA transmission within this nucleus regulates cost/benefit decision making is unknown. We investigated the contribution of DA transmission within the BLA to risk/reward decision making assessed with a probabilistic discounting task. Rats were well-trained to choose between a small/certain reward and a large/risky reward, with the probability of obtaining the larger reward decreasing (100-12.5 %) or increasing (12.5-100 %) over a session. We examined the effects of antagonizing BLA D1 (SCH 23390, 0.1-1 μg) or D2 (eticlopride, 0.1-1 μg) receptors, as well as intra-BLA infusions of agonists for D1 (SKF 81297, 0.1-1 μg) and D2 (quinpirole, 1-10 μg) receptors. We also assessed how DA receptor stimulation may induce differential effects related to baseline levels of risky choice. BLA D1 receptor antagonism reduced risky choice by decreasing reward sensitivity, whereas D2 antagonism did not affect overall choice patterns. Stimulation of BLA D1 receptors optimized decision making in a baseline-dependent manner: in risk-averse rats, infusions of a lower dose of SKF81297 increased risky choice when reward probabilities were high (50 %), whereas in risk-prone rats, this drug reduced risky choice when probabilities were low (12.5 %). Quinpirole reduced risky choice in risk-prone rats, enhancing lose-shift behavior. These data highlight previously uncharacterized roles for BLA DA D1 and D2 receptors in biasing choice during risk/reward decision making through mediation of reward/negative feedback sensitivity.

  5. Dopamine inhibits somatolactin gene expression in tilapia pituitary cells through the dopamine D2 receptors.

    Science.gov (United States)

    Jiang, Quan; Lian, Anji; He, Qi

    2016-07-01

    Dopamine (DA) is an important neurotransmitter in the central nervous system of vertebrates and possesses key hypophysiotropic functions. Early studies have shown that DA has a potent inhibitory effect on somatolactin (SL) release in fish. However, the mechanisms responsible for DA inhibition of SL gene expression are largely unknown. To this end, tilapia DA type-1 (D1) and type-2 (D2) receptor transcripts were examined in the neurointermediate lobe (NIL) of the tilapia pituitary by real-time PCR. In tilapia, DA not only was effective in inhibiting SL mRNA levels in vivo and in vitro, but also could abolish pituitary adenylate cyclase-activating polypeptide (PACAP)- and salmon gonadotropin-releasing hormone (sGnRH)-stimulated SL gene expression at the pituitary level. In parallel studies, the specific D2 receptor agonists quinpirole and bromocriptine could mimic the DA-inhibited SL gene expression. Furthermore, the D2 receptor antagonists domperidone and (-)-sulpiride could abolish the SL response to DA or the D2 agonist quinpirole, whereas D1 receptor antagonists SCH23390 and SKF83566 were not effective in this respect. In primary cultures of tilapia NIL cells, D2 agonist quinpirole-inhibited cAMP production could be blocked by co-treatment with the D2 antagonist domperidone and the ability of forskolin to increase cAMP production was also inhibited by quinpirole. Using a pharmacological approach, the AC/cAMP pathway was shown to be involved in quinpirole-inhibited SL mRNA expression. These results provide evidence that DA can directly inhibit SL gene expression at the tilapia pituitary level via D2 receptor through the AC/cAMP-dependent mechanism. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Vagally mediated effects of brain stem dopamine on gastric tone and phasic contractions of the rat.

    Science.gov (United States)

    Anselmi, L; Toti, L; Bove, C; Travagli, R A

    2017-11-01

    Dopamine (DA)-containing fibers and neurons are embedded within the brain stem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally dependent modulation of gastric tone and phasic contractions, i.e., motility, by DA, however, has not been characterized. With the use of microinjections of DA in the DVC while recording gastric tone and motility, the aims of the present study were 1 ) assess the gastric effects of brain stem DA application, 2 ) identify the DA receptor subtype, and, 3 ) identify the postganglionic pathway(s) activated. Dopamine microinjection in the DVC decreased gastric tone and motility in both corpus and antrum in 29 of 34 rats, and the effects were abolished by ipsilateral vagotomy and fourth ventricular treatment with the selective DA2 receptor antagonist L741,626 but not by application of the selective DA1 receptor antagonist SCH 23390. Systemic administration of the cholinergic antagonist atropine attenuated the inhibition of corpus and antrum tone in response to DA microinjection in the DVC. Conversely, systemic administration of the nitric oxide synthase inhibitor nitro-l-arginine methyl ester did not alter the DA-induced decrease in gastric tone and motility. Our data provide evidence of a dopaminergic modulation of a brain stem vagal neurocircuit that controls gastric tone and motility. NEW & NOTEWORTHY Dopamine administration in the brain stem decreases gastric tone and phasic contractions. The gastric effects of dopamine are mediated via dopamine 2 receptors on neurons of the dorsal motor nucleus of the vagus. The inhibitory effects of dopamine are mediated via inhibition of the postganglionic cholinergic pathway. Copyright © 2017 the American Physiological Society.

  7. Antidepressant-like effect of the extract from leaves of Schinus molle L. in mice: evidence for the involvement of the monoaminergic system.

    Science.gov (United States)

    Machado, Daniele G; Kaster, Manuella P; Binfaré, Ricardo W; Dias, Munique; Santos, Adair R S; Pizzolatti, Moacir G; Brighente, Inês M C; Rodrigues, Ana Lúcia S

    2007-03-30

    Schinus molle L. (Anacardiaceae), among other uses, is popularly employed for the treatment of depression. In this study, the antidepressant-like effect of the hexanic extract from leaves of S. molle was investigated in the mouse tail suspension test (TST), a predictive model of depression. The immobility time in the TST was significantly reduced by the extract (dose range 30-600 mg/kg, p.o.), without accompanying changes in ambulation when assessed in an open-field test. The efficacy of extract was found to be comparable to that of fluoxetine (10 mg/kg, p.o.). The anti-immobility effect of the extract (100 mg/kg, p.o.) was prevented by pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days), NAN-190 (0.5 mg/kg, i.p., a 5-HT(1A) receptor antagonist), WAY100635 (0.1 mg/kg, s.c., a selective 5-HT(1A) receptor antagonist), ketanserin (5 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), MDL72222 (0.1 mg/kg, i.p., a 5-HT(3) receptor antagonist), prazosin (1 mg/kg, i.p., an alpha(1)-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., a D(1) receptor antagonist) or sulpiride (50 mg/kg, i.p., a D(2) receptor antagonist). It may be concluded that the hexanic extract of S. molle produces an antidepressant-like effect that seems to be dependent on its interaction with the serotonergic, noradrenergic and dopaminergic systems. These results provide evidence that the extract from S. molle shares with established antidepressants some pharmacological effects, at least at a preclinical level.

  8. Functional recovery of supersensitive dopamine receptors after intrastriatal grafts of fetal substantia nigra

    International Nuclear Information System (INIS)

    Dawson, T.M.; Dawson, V.L.; Gage, F.H.; Fisher, L.J.; Hunt, M.A.; Wamsley, J.K.

    1991-01-01

    Interruption of the ascending dopamine neurons of the nigrostriatal pathway, by 6-hydroxydopamine (6-OHDA) lesion in rats, produced a significant loss of the dopamine transport complexes labeled with the phencyclidine derivative [3H]BTCP. This loss of dopamine innervation in the striatum was present at least 12 to 14 months after lesioning and was functionally manifested by ipsilateral rotation of the animals in response to amphetamine. In these same animals, in comparison to controls, there was a significant increase in the number (Bmax) of [3H]SCH 23390-labeled D-1 receptors in the striatum (36.7%) and the substantia nigra (35.1%) and a 54.4% increase in the number (Bmax) of [3H]sulpiride-labeled striatal D-2 receptors without an apparent change in affinity (Kd). Ten to twelve months after the transplantation of homologous fetal substantia nigra into the denervated striatum, there was a significant decrease in amphetamine-induced turning behavior. In these animals, there was an ingrowth of dopamine nerve terminals in the striatum as demonstrated by a return of [3H]BTCP binding. Accompanying this reinnervation was the normalization of D-1 and D-2 receptors to control values in the striatum as well as the return of D-1 receptors to prelesion densities in the substantia nigra. In a subgroup of transplanted rats, amphetamine continued to induce ipsilateral turning. In these animals both D-1 and D-2 receptors remained supersensitive. These results support the hypothesis that the functional recovery of transplanted animals is due, in part, to reinnervation of the striatum. In addition, long-term alterations in receptor density may be related to the behavioral deficits that are associated with the 6-OHDA-lesioned rat

  9. Behavioral and neurochemical effects of chronic administration of reserpine and SKF-38393 in rats

    International Nuclear Information System (INIS)

    Neisewander, J.L.; Lucki, I.; McGonigle, P.

    1991-01-01

    Alterations in the density of dopamine receptor subtypes and behaviors mediated by the D1-selective agonist SKF-38393 were examined in rats treated chronically with reserpine, SKF-38393 or the combination of these drugs. Animals received either vehicle or reserpine (1 mg/kg s.c.) on days 1 to 28 and, in addition, half of each of these groups were treated with vehicle and half were treated with SKF-38393 (5-10 mg/kg s.c.) on days 15 to 29. Quantitative autoradiographic measurement of D1 receptors labeled with [ 3 H]SCH-23390 and D2 receptors labeled with [ 3 H]spiroperidol revealed that chronic administration of reserpine increased the density of both receptor subtypes in the nucleus accumbens and caudate-putamen, but not in the substantia nigra. Chronic administration of SKF-38393 alone did not alter D1 receptor density in any of these regions. However, chronic administration of the agonist in reserpinized animals decreased D1 receptor density in the nucleus accumbens, but not in the caudate-putamen or substantia nigra, demonstrating that this partial agonist can selectively down-regulate D1 receptors when endogenous dopaminergic tone is removed. The chronic drug treatments also altered behavioral responses. Chronic administration of SKF-38393 alone produced sensitization of the oral dyskinesia response elicited by a challenge injection of the agonist, but no significant change in the grooming response. Acute administration of SKF-38393 in rats treated with reserpine for 14 days produced stereotypy which was not altered after chronic administration of the agonist. Surprisingly, chronic administration of reserpine alone produced a spontaneous oral dyskinesia, which was blocked dose-dependently by the D2-selective antagonist spiroperidol. These findings are discussed in terms of their relevance to Parkinson's disease and tardive dyskinesia

  10. Antidepressant-like effect of the organoselenium compound ebselen in mice: evidence for the involvement of the monoaminergic system.

    Science.gov (United States)

    Posser, Thaís; Kaster, Manuella P; Baraúna, Sara Cristiane; Rocha, João B T; Rodrigues, Ana Lúcia S; Leal, Rodrigo B

    2009-01-05

    Ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one] is a seleno-organic compound which possesses a potent antioxidant activity and has been shown to exert neuroprotective effects in vitro and in vivo in a variety of pro-oxidative insults. The present study investigates a possible antidepressant activity of ebselen using two predictive tests for antidepressant activity in rodents: the forced swimming test and tail suspension test. Additionally, the mechanisms involved in the antidepressant-like effect of ebselen in mice were also assessed. Ebselen (10 mg/kg, s.c.) decreased the immobility time in the forced swimming test without accompanying changes in ambulation in the open-field test. In contrast, the administration of ebselen (10-30 mg/kg) did not produce any effect in the tail suspension test. The anti-immobility effect of ebselen (10 mg/kg, s.c.) was not prevented by pre-treatment of mice with p-chlorophenylalanine (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, 4 consecutive days), NAN-190 (0.5 mg/kg, i.p., a serotonin 5-HT(1A) receptor antagonist) or ketanserin (5 mg/kg, i.p., a serotonin 5-HT(2A/2C) receptor antagonist). On the other hand, the pre-treatment of mice with prazosin (1 mg/kg, i.p., an alpha(1)-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., a dopamine D(1) receptor antagonist) or sulpiride (50 mg/kg, i.p., a dopamine D(2) receptor antagonist) completely blocked the antidepressant-like effect of ebselen (10 mg/kg, s.c.) in the forced swimming test. It may be concluded that ebselen produces an antidepressant-like effect in the forced swimming test that seems to be dependent on its interaction with the noradrenergic and dopaminergic systems, but not with the serotonergic system.

  11. Role of dopamine receptors in the ventral tegmental area in conditioned fear.

    Science.gov (United States)

    de Oliveira, Amanda Ribeiro; Reimer, Adriano Edgar; Brandão, Marcus Lira

    2009-05-16

    The increased startle reflex in the presence of a stimulus that has been previously paired with footshock has been termed fear-potentiated startle (FPS) and is considered a reliable index of anxiety. Some studies have suggested an association between stressful situations and alterations in dopaminergic (DA) transmission. Many studies converge on the hypothesis that the mesocorticolimbic pathway, originating from DA neurons in the ventral tegmental area (VTA), is particularly sensitive to fear-arousing stimuli. The present study explored the involvement of VTA DA receptors in the acquisition and expression of conditioned fear to a light conditioned stimulus (CS). We evaluated the effects of intra-VTA administration of SKF 38393 (D(1) agonist), SCH 23390 (D(1) antagonist), quinpirole (D(2) agonist), and sulpiride (D(2) antagonist) on FPS. All drugs were administered bilaterally into the VTA (1.0 microg/0.2 microl/site). Locomotor activity/exploration and motor coordination were evaluated in the open-field and rotarod tests. None of the drugs produced significant effects on FPS when injected before conditioning, indicating that VTA DA receptors are not involved in the acquisition of conditioned fear to a light-CS. In contrast, when injected before the test session, quinpirole significantly reduced FPS, whereas the other drugs had no effect. Quinpirole's ability to decrease FPS may be the result of an action on VTA D(2) presynaptic autoreceptors that decrease dopamine levels in terminal fields of the mesocorticolimbic pathway. Altogether, the present results suggest the importance of VTA DA neurons in the fear-activating effects of Pavlovian conditioning. In addition to demonstrating the importance of dopaminergic mechanisms in the motivational consequences of footshock, the present findings also indicate that these neural circuits are mainly involved in the expression, rather than acquisition, of conditioned fear.

  12. Meta-type analysis of dopaminergic effects on gene expression in the neuroendocrine brain of female goldfish

    Directory of Open Access Journals (Sweden)

    Jason T Popesku

    2012-11-01

    Full Text Available Dopamine (DA is a major neurotransmitter important for neuroendocrine control and recent studies have described genomic signalling pathways activated and inhibited by DA agonists and antagonists in the goldfish brain. Here we perform a meta-type analysis using microarray datasets from experiments conducted with female goldfish to characterize the gene expression responses that underlie dopaminergic signalling. Sexually mature, pre-spawning (GSI 4.5 ± 1.3% or sexually regressing ( GSI 3 ± 0.4% female goldfish (15-40 g injected intraperitoneally with either SKF 38393, LY 171555, SCH 23390, sulpiride, or a combination of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and α-methyl-p-tyrosine. Microarray meta-type analysis identified 268 genes in the telencephalon and hypothalamus as having reciprocal (i.e. opposite between agonism and antagonism/depletion fold change responses, suggesting that these transcripts are likely targets for DA-mediated regulation. Noteworthy genes included ependymin, vimentin, and aromatase, genes that support the significance of DA in neuronal plasticity and tissue remodelling. Sub-network enrichment analysis (SNEA was used to identify common gene regulators and binding proteins associated with the differentially expressed genes mediated by DA. SNEA analysis identified gene expression targets that were related to three major categories that included cell signalling (STAT3, SP1, SMAD, Jun/Fos, immune response (IL6, IL1β, TNFs, cytokine, NF-κB, and cell proliferation and growth (IGF1, TGFβ1. These gene networks are also known to be associated with neurodegenerative disorders such as Parkinsons’ disease, well-known to be associated with loss of dopaminergic neurons. This study identifies genes and networks that underlie DA signalling in the vertebrate CNS and provides targets that may be key neuroendocrine regulators. The results provide a foundation for future work on dopaminergic regulation of gene expression in fish

  13. Substantiation for Approaches to Treatment of Latent Autoimmune Diabetes in Adults

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    T.M. Tykhonova

    2014-10-01

    Conclusions. Analysis of carbohydrate metabolism on the manifestation stage and over time development of latent autoimmune diabetes in adults as well as reduction of β-cells insulin-producing function associated with autoimmune insulitis and progressing while the development of this form of disease, substantiate the rational for insulin administration as this form of diabetes has been diagnosed. If patients with latent autoimmune diabetes in adults have metabolic syndrome clusters it is quite reasonable to add metformin to insulin.

  14. Diagnosis and Management of Subclinical Hypothyroidism in Elderly Adults: A Review of the Literature.

    Science.gov (United States)

    Hennessey, James V; Espaillat, Ramon

    2015-08-01

    The estimated prevalence of subclinical hypothyroidism (SCH) in the general population is 3% to 8%. As the average age of the population in the United States and other countries continues to increase, the overall prevalence of SCH may also be expected to increase. Although age-related changes in thyroid function are well described, normal thyroid-stimulating hormone (TSH) reference limits, derived for age-specific populations, are not routinely used to identify thyroid dysfunction in elderly adults. Therefore, currently accepted values for the upper limit of normal of TSH may be inappropriate for diagnosing SCH in individuals aged 65 and older, resulting in potential overestimation of the prevalence of SCH in this population. This review discusses the current evidence of the effects of SCH on cardiovascular health and neuropsychiatric function in older adults. Although the results of some studies are conflicting, the overall evidence suggests that the consequences of SCH may be different for elderly adults than for younger populations. Treatment of SCH in older individuals requires special consideration with regard to thyroid hormone replacement therapy and expected clinical outcomes. Although careful identification of individuals with persistent SCH who could benefit from levothyroxine treatment is necessary, current evidence suggests that individuals with TSH levels greater than 10 mIU/L who test positive for antithyroid antibodies or are symptomatic may benefit from levothyroxine treatment to reduce the risk of progression to overt hypothyroidism, decrease the risk of adverse cardiovascular events, and improve their quality of life. After treatment is initiated, careful monitoring is essential. © 2015, The Authors. The Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society.

  15. Causes for contemporary regional sea level changes.

    Science.gov (United States)

    Stammer, Detlef; Cazenave, Anny; Ponte, Rui M; Tamisiea, Mark E

    2013-01-01

    Regional sea level changes can deviate substantially from those of the global mean, can vary on a broad range of timescales, and in some regions can even lead to a reversal of long-term global mean sea level trends. The underlying causes are associated with dynamic variations in the ocean circulation as part of climate modes of variability and with an isostatic adjustment of Earth's crust to past and ongoing changes in polar ice masses and continental water storage. Relative to the coastline, sea level is also affected by processes such as earthquakes and anthropogenically induced subsidence. Present-day regional sea level changes appear to be caused primarily by natural climate variability. However, the imprint of anthropogenic effects on regional sea level-whether due to changes in the atmospheric forcing or to mass variations in the system-will grow with time as climate change progresses, and toward the end of the twenty-first century, regional sea level patterns will be a superposition of climate variability modes and natural and anthropogenically induced static sea level patterns. Attribution and predictions of ongoing and future sea level changes require an expanded and sustained climate observing system.

  16. Thickening of the epicardial adipose tissue can be alleviated by thyroid hormone replacement therapy in patients with subclinical hypothyroidism.

    Science.gov (United States)

    Sayin, Irmak; Erkan, Aycan Fahri; Ekici, Berkay; Kutuk, Utku; Corakci, Ahmet; Tore, Hasan Fehmi

    2016-01-01

    Subclinical hypothyroidism (SCH) is a common disorder which has adverse cardiovascular effects. Epicardial adipose tissue (EAT), a novel marker of cardiovascular risk, is increased in SCH. We aimed to investigate whether L-thyroxine treatment can reverse the thickening of EAT in SCH. Forty-four patients with SCH and 42 euthyroid control subjects were included. EAT thickness was measured using transthoracic echocardiography at baseline and after restoration of the euthyroid status with 3 months of L-thyroxine treatment. At baseline, mean EAT thickness was significantly greater in the SCH group when compared to the control group (6.3 ± 1.7 mm vs. 4.1 ± 0.9 mm, respectively, p treatment (6.3 ± 1.7 mm vs. 5.1 ± 1.4 mm, p treatment when compared to baseline (DEAT) significantly correlated to the difference in TSH levels before and after treatment (DTSH; r = 0.323; p = 0.032). Epicardial adipose tissue thickness is increased in patients with SCH. This thickening was alleviated with restoration of the euthyroid status with L-thyroxine treatment in our study population of predominantly male, relatively old subjects with greater baseline EAT thickness.

  17. Subclinical Hypothyroidism in PCOS: Impact on Presentation, Insulin Resistance, and Cardiovascular Risk

    Directory of Open Access Journals (Sweden)

    Qun Yu

    2016-01-01

    Full Text Available Aim of Study. To assess status of thyroid function and thyroid disorders particularly subclinical hypothyroidism (SCH in subjects with polycystic ovarian syndrome (PCOS and impact of SCH on various clinical and biochemical parameters and cardiovascular risk in PCOS. Methods. Hundred females diagnosed with PCOS as per Rotterdam criteria and 100 normal controls were recruited and were subjected to elaborate anthropometric, clinical, and biochemical assessment. Results. Notable findings included significantly higher frequency of subjects with subclinical hypothyroidism (p=0.0002, autoimmune thyroiditis (p<0.001, and goitre (p=0.02 in polycystic ovarian syndrome subjects compared to control subjects. Further SCH PCOS subjects were found to harbor significantly higher HOMA-IR (p<0.05 and frequency of subjects with dyslipidemia (p<0.05 compared to both euthyroid PCOS and euthyroid control subjects. Though frequency of subjects with cardiovascular risk factors was higher in SCH PCOS group than euthyroid PCOS group, it failed to reach statistical significance. Conclusion. We concluded that PCOS is associated with high incidence of SCH and AIT compared to normal population and SCH poses increased risk of cardiovascular disorder in PCOS.

  18. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to acetyl-L-carnitine and contribution to normal cognitive function (ID 1432) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    claims in relation to acetyl-L-carnitine and contribution to normal cognitive function. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims and references that EFSA has received from Member States or directly from......Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006. This opinion addresses the scientific substantiation of health...... be drawn for the scientific substantiation of the claim. On the basis of the data presented, the Panel concludes that a cause and effect relationship has not been established between the consumption of acetyl-L-carnitine and contribution to normal cognitive function....

  19. Causes and prevention of sudden cardiac death in the elderly.

    Science.gov (United States)

    Tung, Patricia; Albert, Christine M

    2013-03-01

    Sudden cardiac death (SCD) is a major cause of mortality in elderly individuals owing to a high prevalence of coronary heart disease, systolic dysfunction, and congestive heart failure (CHF). Although the incidence of SCD increases with age, the proportion of cardiac deaths that are sudden decreases owing to high numbers of other cardiac causes of death in elderly individuals. Implantable cardioverter-defibrillator (ICD) therapy has been demonstrated to improve survival and prevent SCD in selected patients with systolic dysfunction and CHF. However, ICD therapy in elderly patients might not be effective because of a greater rate of pulseless electrical activity underlying SCD and other competing nonarrhythmic causes of death in this population. Although under-represented in randomized trials of ICD use, elderly patients comprise a substantial proportion of the population that qualifies for and receives an ICD for primary prevention under current guidelines. Cardiac resynchronization therapy (CRT), which has been demonstrated to reduce mortality in selected populations with heart failure, is also more commonly used in this group of patients than in younger individuals. In this Review, we examine the causes of SCD in elderly individuals, and discuss the existing evidence for effectiveness of ICD therapy and CRT in this growing population.

  20. Association between subclinical hypocalcemia in the first 3 days of lactation and reproductive performance of dairy cows.

    Science.gov (United States)

    Caixeta, L S; Ospina, P A; Capel, M B; Nydam, D V

    2017-05-01

    The objective of this study was to determine the effects of subclinical hypocalcemia on reproductive performance in dairy cows. In a prospective cohort study, 97 cows on 2 dairy farms with automatic milking systems were monitored for subclinical hypocalcemia. Animals were enrolled 7 ± 3 days prior to estimated calving date and three parity groups were defined based on the lactation that the animals were going to start: lactation = 1, lactation = 2, and lactation ≥3. Serum calcium concentration (Ca) was measured in all animals in the first 3 DIM and subclinical hypocalcemia (SCH) was defined as Ca ≤ 8.6 mg/dL; animals that presented a low Ca level during all 3 days were classified as chronic SCH (cSCH). Return to cyclicity during the voluntary waiting period was analyzed based on weekly progesterone concentrations measured in serum. Information on reproductive outcomes (i.e., number of breedings, pregnancy status, days open, etc.), were collected from on-farm software after all study cows had completed their study period. Chronic SCH was present in all parity groups with higher incidence in multiparous animals (20% of parity = 1, 32% of parity = 2; and 46% of parity ≥ 3 animals). The cSCH animals took longer to show active ovaries when compared to eucalcemic and SCH animals. In a multivariable Cox's Proportional Hazard model animals with normal Ca were 1.8 times more likely to return to cyclicity by the end of the voluntary waiting period when compared to cSCH animals. Animals with cSCH also had 0.27 odds of being pregnant at first service compared to eucalcemic cows when analyzed by multivariable logistic regression. Subclinical hypocalcemia had a negative effect on return of ovarian function during the voluntary waiting period and decreased the odds of pregnancy at first service. Those cows with cSCH had an even more pronounced impaired reproductive function than those with one subclinical measurement. Copyright © 2017 Elsevier Inc. All