Hypnotizability, hypnosis and prepulse inhibition of the startle reflex in healthy women: an ERP analysis.

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De Pascalis, Vilfredo; Russo, Emanuela

2013-01-01

A working model of the neurophysiology of hypnosis suggests that highly hypnotizable individuals (HHs) have more effective frontal attentional systems implementing control, monitoring performance, and inhibiting unwanted stimuli from conscious awareness, than low hypnotizable individuals (LHs). Recent studies, using prepulse inhibition (PPI) of the auditory startle reflex (ASR), suggest that HHs, in the waking condition, may show reduced sensory gating although they may selectively attend and disattend different stimuli. Using a within subject design and a strict subject selection procedure, in waking and hypnosis conditions we tested whether HHs compared to LHs showed a significantly lower inhibition of the ASR and startle-related brain activity in both time and intracerebral source localization domains. HHs, as compared to LH participants, exhibited (a) longer latency of the eyeblink startle reflex, (b) reduced N100 responses to startle stimuli, and (c) higher PPI of eyeblink startle and of the P200 and P300 waves. Hypnosis yielded smaller N100 waves to startle stimuli and greater PPI of this component than in the waking condition. sLORETA analysis revealed that, for the N100 (107 msec) elicited during startle trials, HHs had a smaller activation in the left parietal lobe (BA2/40) than LHs. Auditory pulses of pulse-with prepulse trials in HHs yielded less activity of the P300 (280 msec) wave than LHs, in the cingulate and posterior cingulate gyrus (BA23/31). The present results, on the whole, are in the opposite direction to PPI findings on hypnotizability previously reported in the literature. These results provide support to the neuropsychophysiological model that HHs have more effective sensory integration and gating (or filtering) of irrelevant stimuli than LHs.

Association between prepulse inhibition of the startle response and latent inhibition of two-way avoidance acquisition: A study with heterogeneous NIH-HS rats.

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Sánchez-González, Ana; Esnal, Aitor; Río-Álamos, Cristóbal; Oliveras, Ignasi; Cañete, Toni; Blázquez, Gloria; Tobeña, Adolf; Fernández-Teruel, Alberto

2016-03-01

This study presents the first evaluation of the associations between responses in two paradigms related to schizophrenia in the genetically heterogeneous NIH-HS rat stock. NIH-HS rats are a stock of genetically heterogeneous animals that have been derived from eight different inbred strains. A rotational breeding schedule has been followed for more than eighty generations, leading to a high level of genetic recombination that makes the NIH-HS rats a unique tool for studying the genetic basis of (biological, behavioral, disease-related) complex traits. Previous work has dealt with the characterization of coping styles, cognitive and anxiety/fear-related profiles of NIH-HS rats. In the present study we have completed their characterization in two behavioral models, prepulse inhibition (PPI) and latent inhibition (LI) of the two-way active avoidance response, that appear to be related to schizophrenia or to schizophrenia-relevant symptoms. We have found that these rats display PPI for each of the four prepulse intensities tested, allowing their stratification in high, medium and low PPI subgroups. When testing these three subgroups for LI of two-way active avoidance acquisition it has been observed that the LowPPI and MediumPPI subgroups present impaired LI, which, along with the fact that the HighPPI group presents significant LI, allows us to hypothesize that responses in these two paradigms are somehow related and that selection of NIH-HS rats for Low vs HighPPI could make a promising animal model for the study of clusters of schizophrenia-relevant symptoms and their underlying neurobiological mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

Routine post-weaning handling of rats prevents isolation rearing-induced deficit in prepulse inhibition

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M.L.N.M. Rosa

2005-11-01

Full Text Available Rats reared under isolation conditions from weaning present a number of behavioral changes compared to animals reared under social conditions (group housing. These changes include deficits in prepulse inhibition (PPI of the startle reflex to a loud sound. PPI refers to the reduction of the magnitude of the startle reflex when a relatively weak stimulus (the prepulse precedes by an appropriate time interval the intense startle-elicing stimulus (the pulse. PPI is useful for studying sensorimotor integration. The present study evaluated the effect of handling on the impairment of PPI induced by isolation-rearing. Male Wistar rats (N = 11-15/group were housed in groups (5 per cage and handled three times a week or isolated (housed individually since weaning (21 days for 10 weeks when they reach approximately 150 g. The isolated rats were divided into "minimally handled" animals (handled once a week for cleaning purposes only or "handled" animals (handled three times a week. This handling consisted of grasping the rat by the tail and moving it to a clean cage (approximately 5 s. A statistically significant reduction (52% in the PPI test was found only in the isolated group with minimal handling while no difference was seen between grouped animals and isolated handled animals. These results indicate that isolation rearing causes disruption in the PPI at adult age, which serves as an index of attention deficit. This change in the sensory processing of information induced by post-weaning isolation can be prevented by handling during the development of the animal.

Routine post-weaning handling of rats prevents isolation rearing-induced deficit in prepulse inhibition.

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Rosa, M L N M; Silva, R C B; Moura-de-Carvalho, F T; Brandão, M L; Guimarães, F S; Del Bel, E A

2005-11-01

Rats reared under isolation conditions from weaning present a number of behavioral changes compared to animals reared under social conditions (group housing). These changes include deficits in prepulse inhibition (PPI) of the startle reflex to a loud sound. PPI refers to the reduction of the magnitude of the startle reflex when a relatively weak stimulus (the prepulse) precedes by an appropriate time interval the intense startle-elicing stimulus (the pulse). PPI is useful for studying sensorimotor integration. The present study evaluated the effect of handling on the impairment of PPI induced by isolation-rearing. Male Wistar rats (N = 11-15/group) were housed in groups (5 per cage and handled three times a week) or isolated (housed individually) since weaning (21 days) for 10 weeks when they reach approximately 150 g. The isolated rats were divided into "minimally handled" animals (handled once a week for cleaning purposes only) or "handled" animals (handled three times a week). This handling consisted of grasping the rat by the tail and moving it to a clean cage (approximately 5 s). A statistically significant reduction (52%) in the PPI test was found only in the isolated group with minimal handling while no difference was seen between grouped animals and isolated handled animals. These results indicate that isolation rearing causes disruption in the PPI at adult age, which serves as an index of attention deficit. This change in the sensory processing of information induced by post-weaning isolation can be prevented by handling during the development of the animal.

Hypnotizability, hypnosis and prepulse inhibition of the startle reflex in healthy women: an ERP analysis.

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Vilfredo De Pascalis

Full Text Available A working model of the neurophysiology of hypnosis suggests that highly hypnotizable individuals (HHs have more effective frontal attentional systems implementing control, monitoring performance, and inhibiting unwanted stimuli from conscious awareness, than low hypnotizable individuals (LHs. Recent studies, using prepulse inhibition (PPI of the auditory startle reflex (ASR, suggest that HHs, in the waking condition, may show reduced sensory gating although they may selectively attend and disattend different stimuli. Using a within subject design and a strict subject selection procedure, in waking and hypnosis conditions we tested whether HHs compared to LHs showed a significantly lower inhibition of the ASR and startle-related brain activity in both time and intracerebral source localization domains. HHs, as compared to LH participants, exhibited (a longer latency of the eyeblink startle reflex, (b reduced N100 responses to startle stimuli, and (c higher PPI of eyeblink startle and of the P200 and P300 waves. Hypnosis yielded smaller N100 waves to startle stimuli and greater PPI of this component than in the waking condition. sLORETA analysis revealed that, for the N100 (107 msec elicited during startle trials, HHs had a smaller activation in the left parietal lobe (BA2/40 than LHs. Auditory pulses of pulse-with prepulse trials in HHs yielded less activity of the P300 (280 msec wave than LHs, in the cingulate and posterior cingulate gyrus (BA23/31. The present results, on the whole, are in the opposite direction to PPI findings on hypnotizability previously reported in the literature. These results provide support to the neuropsychophysiological model that HHs have more effective sensory integration and gating (or filtering of irrelevant stimuli than LHs.

Acoustic startle reflex and pre-pulse inhibition in tinnitus patients

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Kelly Shadwick; Wei Sun

2014-01-01

Gap induced pre-pulse inhibition (Gap-PPI) of acoustic startle reflex has been used as a measurement of tinnitus in animal models. However, whether this test is sensitive to detect tinnitus in humans is still unclear. Based on the testing procedure used in animal studies, a human subject testing method was formulated and conducted to investigate if a similar result could be found in tinnitus patients. Audiologic and tinnitus assessments and acoustic startle reflex measurements were performed on seven tinnitus subjects and nine age matched subjects without tinnitus. There was no significant difference found between the control and tinnitus group on the Gap-PPI across the frequencies evaluated. The amplitude of the startle response in the tinnitus group with normal hearing thresholds was significantly higher than the control group and those with tinnitus and hearing loss. This preliminary result suggests that hyperexcitability in the central auditory system may be involved in tinnitus. There was no correlation between hearing thresholds and the increased amplitude of startle response.

Effects of melatonin on prepulse inhibition, habituation and sensitization of the human startle reflex in healthy volunteers

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Lehtinen, Emilia K; Ucar, Ebru; Glenthøj, Birte Y

2014-01-01

Prepulse inhibition of the startle reflex (PPI) is an operational measure of sensorimotor gating, which is demonstrated to be impaired in patients with schizophrenia. In addition, a disruption of the circadian rhythm together with blunted melatonin secretion is regularly found in patients...... with schizophrenia and it is theorized that these may contribute to their attentional deficits. The aim of this study was to assess the effects of acute melatonin on healthy human sensorimotor gating. Twenty-one healthy male volunteers were administered melatonin or placebo after which their levels of PPI were...... assessed. Melatonin significantly reduced startle magnitude and ratings of alertness, but did not influence PPI, nor sensitization and habituation. However, when taking baseline scores in consideration, melatonin significantly increased PPI in low scoring individuals while significantly decreasing...

Neural circuits containing olfactory neurons are involved in prepulse inhibition of the startle reflex in rats

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Haichen eNiu

2015-03-01

Full Text Available Many neuropsychiatric disorders, such as schizophrenia, have been associated with abnormalities in the function of the olfactory system and prepulse inhibition (PPI of the startle reflex. However, whether these two abnormalities are related is unclear. The present study was designed to determine whether inhibiting olfactory sensory input via the infusion of zinc sulfate (ZnE, 0.17 M, 0.5 ml into the olfactory naris disrupts PPI. Furthermore, lidocaine/MK801 was bilaterally microinjected into the olfactory bulb (OB to examine whether the blockade of olfactory sensory input impairs PPI. To identify the neural projections that connect the olfaction- and PPI-related areas of the CNS, trans-synaptic retrograde tracing using a recombinant pseudorabies virus (PRV was performed. Our results demonstrated that blocking olfactory sensory input altered olfaction-related behavior. At the functional level, we demonstrated that the inhibition of olfactory sensory input impaired PPI of the startle response subsequent to a decrease in c-fos expression in relevant brain regions. Furthermore, the results of a similar and more robust experiment indicated that blocking olfactory sensory input via the microinjection of lidocaine/MK801 into the OB impaired PPI. At the circuit level, based on trans-synaptic retrograde tracing using PRV, we demonstrated that a large portion of the labeled neurons in several regions of the olfactory cortices connected to the pedunculopontine tegmental nucleus (PPTg. Thus, these data suggest that the olfactory system participates in the regulation of PPI and plays a role in the effect of PPI on the startle response in rats.

Increased Prepulse Inhibition and Sensitization of the Startle Reflex in Autistic Children

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Madsen, Gitte Falcher; Bilenberg, Niels; Cantio, Cathriona

2014-01-01

The relation between autism spectrum disorders (ASD) and schizophrenia is a subject of intense debate and research due to evidence of common neurobiological pathways in the two disorders. The objective of this study was to explore whether deficits in prepulse inhibition (PPI) of the startle reflex......, as usually seen in schizophrenic patients, can be replicated in a group of children with ASD in comparison with a group of matched neuro-typically developed (NTD) controls. An additional aim was to explore possible psychophysiological subgroups within our ASD sample. In a case-control design, 35 ASD patients...... and 40 matched NTD controls were tested in a psychophysiological test battery. The PPI of the acoustic startle reflex was analyzed in 18 ASD subjects and 34 NTD controls. Habituation and sensitization were analyzed in 23 ASD subjects and 39 NTD controls. In trials with less intense prestimuli (76 d...

Alterations to prepulse inhibition magnitude and latency in adult rats following neonatal treatment with domoic acid and social isolation rearing.

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Marriott, Amber L; Tasker, R Andrew; Ryan, Catherine L; Doucette, Tracy A

2016-02-01

Deficits in perceptual, informational, and attentional processing are consistently identified as a core feature in schizophrenia and related neuropsychiatric disorders. Neonatal injections of low doses of the AMPA/kainate agonist domoic acid (DOM) have previously been shown to alter various aspects of perceptual and attentional processing in adult rats. The current study investigated the effects of combined neonatal DOM treatment with isolation rearing on prepulse inhibition behaviour and relevant neurochemical measures, to assess the usefulness of these paradigms in modeling neurodevelopmental disorders. Daily subcutaneous injections of DOM (20 μg/kg) or saline were administered to male and female rat pups from postnatal days (PND) 8-14. After weaning, rats were either housed alone or in groups of 4. Both the magnitude and latency of prepulse inhibition were determined in adulthood (approximately 4.5 months of age) and post-mortem brain tissue was assayed using Western blot. Social isolation alone significantly lowered PPI magnitude in male (but not female) rats while DOM treatment appeared to make animals refractory to this effect. Combining social isolation and DOM treatment caused an additive decrease in PPI startle latency. No statistically significant differences were found in the expression of D1, D2, TH, GAD65 or GAD67 protein in either the prefrontal cortex or hippocampus, although some tendencies toward differences were noted. We conclude that both neonatal low-dose DOM and social isolation affect prepulse inhibition in rats but that each paradigm exerts these effects through different neuronal signalling systems. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of sigma(1) receptor ligand, MS-377 on apomorphine- or phencyclidine-induced disruption of prepulse inhibition of acoustic startle in rats.

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Yamada, S; Yamauchi, K; Hisatomi, S; Annoh, N; Tanaka, M

2000-08-25

To evaluate the antipsychotic property of a sigma(1) receptor ligand, (R)-(+)-1-(4-chlorophenyl)-3-¿4-(2-methoxyethyl)piperazin-1-yl¿ methyl-2-pyrrolidinone-L-tartrate (MS-377), an antagonistic effect of MS-377 on the disruption of prepulse inhibition (PPI) of the acoustic startle by apomorphine or phencyclidine (PCP) was investigated in rats. MS-377 antagonized the PCP-induced disruption of PPI. The ED(50) value of MS-377 for this effect was 0.66 mg/kg. In contrast, apomorphine-induced disruption of PPI was not attenuated by MS-377. These data indicate that the PCP-induced disruption of PPI in rats would be, at least partially, mediated by sigma receptors and MS-377 could be a novel anti-psychotic agent with clinical efficacy for the sensorimotor-gating deficit in schizophrenia.

Inhibition in the Human Auditory Cortex.

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Koji Inui

Full Text Available Despite their indispensable roles in sensory processing, little is known about inhibitory interneurons in humans. Inhibitory postsynaptic potentials cannot be recorded non-invasively, at least in a pure form, in humans. We herein sought to clarify whether prepulse inhibition (PPI in the auditory cortex reflected inhibition via interneurons using magnetoencephalography. An abrupt increase in sound pressure by 10 dB in a continuous sound was used to evoke the test response, and PPI was observed by inserting a weak (5 dB increase for 1 ms prepulse. The time course of the inhibition evaluated by prepulses presented at 10-800 ms before the test stimulus showed at least two temporally distinct inhibitions peaking at approximately 20-60 and 600 ms that presumably reflected IPSPs by fast spiking, parvalbumin-positive cells and somatostatin-positive, Martinotti cells, respectively. In another experiment, we confirmed that the degree of the inhibition depended on the strength of the prepulse, but not on the amplitude of the prepulse-evoked cortical response, indicating that the prepulse-evoked excitatory response and prepulse-evoked inhibition reflected activation in two different pathways. Although many diseases such as schizophrenia may involve deficits in the inhibitory system, we do not have appropriate methods to evaluate them; therefore, the easy and non-invasive method described herein may be clinically useful.

Sleep duration, depression, and oxytocinergic genotype influence prepulse inhibition of the startle reflex in postpartum women.

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Comasco, Erika; Gulinello, Maria; Hellgren, Charlotte; Skalkidou, Alkistis; Sylven, Sara; Sundström-Poromaa, Inger

2016-04-01

The postpartum period is characterized by a post-withdrawal hormonal status, sleep deprivation, and susceptibility to affective disorders. Postpartum mothering involves automatic and attentional processes to screen out new external as well as internal stimuli. The present study investigated sensorimotor gating in relation to sleep duration, depression, as well as catecholaminergic and oxytocinergic genotypes in postpartum women. Prepulse inhibition (PPI) of the startle reflex and startle reactivity were assessed two months postpartum in 141 healthy and 29 depressed women. The catechol-O-methyltransferase (COMT) Val158Met, and oxytocin receptor (OXTR) rs237885 and rs53576 polymorphisms were genotyped, and data on sleep duration were collected. Short sleep duration (less than four hours in the preceding night) and postpartum depression were independently associated with lower PPI. Also, women with postpartum depression had higher startle reactivity in comparison with controls. The OXTR rs237885 genotype was related to PPI in an allele dose-dependent mode, with T/T healthy postpartum women carriers displaying the lowest PPI. Reduced sensorimotor gating was associated with sleep deprivation and depressive symptoms during the postpartum period. Individual neurophysiological vulnerability might be mediated by oxytocinergic genotype which relates to bonding and stress response. These findings implicate the putative relevance of lower PPI of the startle response as an objective physiological correlate of liability to postpartum depression. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Stability of prepulse inhibition and habituation of the startle reflex in schizophrenia: a 6-year follow-up study of initially antipsychotic-naive, first-episode schizophrenia patients

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Hammer, Trine Bjørg; Oranje, Bob; Fagerlund, Birgitte

2011-01-01

and is regarded as an endophenotype for schizophrenia. However, reports on the stability of PPI over a longer period of time are lacking, both for patients with schizophrenia and for healthy subjects. The current study examined 25 initially drug-naive, first-episode schizophrenia patients and 23 healthy matched...... not change in patients or controls. The present results show that PPI in drug-naive, first-episode schizophrenia patients can improve significantly over time. As PPI increased in patients over the same period that it decreased in controls, it is likely that the increase was caused by disease-related factors......Deficits in information processing appear to be core features in the pathogenesis of schizophrenia. Prepulse inhibition (PPI) and habituation of the startle reflex are operational measures of early information processing. Impaired PPI in schizophrenia has been replicated in many studies...

Clerodendrum inerme Leaf Extract Alleviates Animal Behaviors, Hyperlocomotion, and Prepulse Inhibition Disruptions, Mimicking Tourette Syndrome and Schizophrenia

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Hon-Lie Chen

2012-01-01

Full Text Available Previously, we found a patient with intractable motor tic disorder, a spectrum of Tourette syndrome (TS, responsive to the ground leaf juice of Clerodendrum inerme (CI. Here, we examined the effect of the ethanol extract of CI leaves (CI extract on animal behaviors mimicking TS, hyperlocomotion, and sensorimotor gating deficit. The latter is also observed in schizophrenic patients and can be reflected by a disruption of prepulse inhibition of acoustic startle response (PPI in animal models induced by methamphetamine and NMDA channel blockers (ketamine or MK-801, based on hyperdopaminergic and hypoglutamatergic hypotheses, respectively. CI extract (10–300 mg/kg, i.p. dose-dependently inhibited hyperlocomotion induced by methamphetamine (2 mg/kg, i.p. and PPI disruptions induced by methamphetamine, ketamine (30 mg/kg, i.p., and MK-801 (0.3 mg/kg, i.p. but did not affect spontaneous locomotor activity, rotarod performance, and grip force. These results suggest that CI extract can relieve hyperlocomotion and improve sensorimotor gating deficit, supporting the therapeutic potential of CI for TS and schizophrenia.

The effects of imipramine on P50 suppression, prepulse inhibition and habituation of the startle response in humans

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Hammer, Trine Bjørg; Oranje, Bob; Glenthoj, Birte Y

2007-01-01

Schizophrenic patients exhibit impairments in filtering of sensory information, as can be assessed by use of prepulse inhibition (PPI) of the acoustic startle response and P50 suppression paradigms. In the treatment of negative symptoms or depressive syndromes during the course of schizophrenia...... as well as P50 suppression. No significant differences between the two treatments were observed on habituation of the acoustic startle reflex. Since sensory filtering is usually already reduced in patients with schizophrenia, the current results call for caution in the widespread use of dual......-acting antidepressants in the treatment of depressed or negative symptoms in these patients....

Assessment of auditory sensory processing in a neurodevelopmental animal model of schizophrenia-Gating of auditory-evoked potentials and prepulse inhibition

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Broberg, Brian Villumsen; Oranje, Bob; Yding, Birte

2010-01-01

The use of translational approaches to validate animal models is needed for the development of treatments that can effectively alleviate cognitive impairments associated with schizophrenia, which are unsuccessfully treated by the current available therapies. Deficits in pre-attentive stages...... of sensory information processing seen in schizophrenia patients, can be assessed by highly homologues methods in both humans and rodents, evident by the prepulse inhibition (PPI) of the auditory startle response and the P50 (termed P1 here) suppression paradigms. Treatment with the NMDA receptor antagonist...... PCP on postnatal days 7, 9, and 11 reliably induce cognitive impairments resembling those presented by schizophrenia patients. Here we evaluate the potential of early postnatal PCP (20mg/kg) treatment in Lister Hooded rats to induce post-pubertal deficits in PPI and changes, such as reduced gating...

Adenosine AA Receptor Antagonists Do Not Disrupt Rodent Prepulse Inhibition: An Improved Side Effect Profile in the Treatment of Parkinson's Disease

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Carina J. Bleickardt

2012-01-01

Full Text Available Parkinson's disease (PD is characterized by loss of dopaminergic neurons in the substantia nigra. Current treatments for PD focus on dopaminergic therapies, including L-dopa and dopamine receptor agonists. However, these treatments induce neuropsychiatric side effects. Psychosis, characterized by delusions and hallucinations, is one of the most serious such side effects. Adenosine A2A receptor antagonism is a nondopaminergic treatment for PD with clinical and preclinical efficacy. The present studies assessed A2A antagonists SCH 412348 and istradefylline in rodent prepulse inhibition (PPI, a model of psychosis. Dopamine receptor agonists pramipexole (0.3–3 mg/kg, pergolide (0.3–3 mg/kg, and apomorphine (0.3–3 mg/kg significantly disrupted PPI; ropinirole (1–30 mg/kg had no effect; L-dopa (100–300 mg/kg disrupted rat but not mouse PPI. SCH 412348 (0.3–3 mg/kg did not disrupt rodent PPI; istradefylline (0.1–1 mg/kg marginally disrupted mouse but not rat PPI. These results suggest that A2A antagonists, unlike dopamine agonists, have an improved neuropsychiatric side effect profile.

Prepulse inhibition is associated with attention, processing speed, and 123I-FP-CIT SPECT in Parkinson's disease

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Zoetmulder, Marielle; Biernat, Heidi B; Nikolic, Miki

2014-01-01

BACKGROUND: Prepulse inhibition is a measure of sensorimotor gating, which reflects the ability to filter or 'gate' irrelevant information. Prepulse inhibition is dramatically altered in basal ganglia disorders associated with dysfunction in the midbrain dopaminergic system, and corresponding......'s disease have been extensively studied in relation to motor function, less is known about the potential role of sensorimotor processes in cognitive function. OBJECTIVE: We investigated the relationship between prepulse inhibition, cognition and nigrostriatal dysfunction, as measured with 123I......-FP-CIT-SPECT scanning, in patients with Parkinson's disease. METHODS: 38 Parkinson patients were assessed with prepulse inhibition, neuropsychological tests, and neurological investigation. A subset of these patients underwent 123I-FP-CIT-SPECT scanning. RESULTS: Patients with a higher level of prepulse inhibition...

BDNF deficiency and young-adult methamphetamine induce sex-specific effects on prepulse inhibition regulation

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Elizabeth E Manning

2013-06-01

Full Text Available Brain-derived neurotrophic factor (BDNF has been implicated in the pathophysiology of schizophrenia, yet its role in the development of specific symptoms is unclear. Methamphetamine (METH users have an increased risk of psychosis and schizophrenia, and METH-treated animals have been used extensively as a model to study the positive symptoms of schizophrenia. We investigated whether METH treatment in BDNF heterozygous mutant mice (HET has cumulative effects on sensorimotor gating, including the disruptive effects of psychotropic drugs. BDNF HETs and WT littermates were treated during young-adulthood with METH and, following a two-week break, prepulse inhibition (PPI was examined. At baseline, BDNF HETs showed reduced PPI compared to WT mice irrespective of METH pre-treatment. An acute challenge with amphetamine (AMPH disrupted PPI but male BDNF HETs were more sensitive to this effect, irrespective of METH pre-treatment. In contrast, female mice treated with METH were less sensitive to the disruptive effects of AMPH, and there were no effects of BDNF genotype. Similar changes were not observed in the response to an acute apomorphine or MK-801 challenge. These results show that genetically-induced reduction of BDNF caused changes in a behavioural endophenotype relevant to the positive symptoms of schizophrenia. However, major sex differences were observed in the effects of a psychotropic drug challenge on this behaviour. These findings suggest sex differences in the effects of BDNF depletion and METH treatment on the monoamine signaling pathways that regulate PPI. Given that these same pathways are thought to contribute to the expression of positive symptoms in schizophrenia, this work suggests that there may be significant sex differences in the pathophysiology underlying these symptoms. Elucidating these sex differences may be important for our understanding of the neurobiology of schizophrenia and developing better treatments strategies for the

Subchronic and chronic PCP treatment produces temporally distinct deficits in attentional set shifting and prepulse inhibition in rats.

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Egerton, Alice; Reid, Lee; McGregor, Sandie; Cochran, Susan M; Morris, Brian J; Pratt, Judith A

2008-05-01

We have previously demonstrated that subchronic (five daily administrations of 2.6 mg/kg PCP) and chronic intermittent administration of 2.6 mg/kg PCP to rats produces hypofrontality and other neurochemical changes akin to schizophrenia pathology (Cochran et al., Neuropsychopharmacology, 28:265-275, 2003). We sought to determine whether behavioral alterations related to discrete aspects of schizophrenia are also induced by these PCP treatment regimes. Following administration of vehicle or PCP according to the protocols described above, rats were assessed for attentional set shifting ability, prepulse inhibition (PPI), or social interaction and the locomotor response to a challenge dose of amphetamine. Ability to shift attentional set was impaired 72 h after the last PCP administration following the subchronic and chronic intermittent treatment regimes. PPI was disrupted after each acute administration of PCP in animals under the subchronic treatment regime. However, PPI deficits were not sustained 72 h after the last of five daily administrations. In subchronic and chronic PCP treated animals, no change was found in social interaction behavior, and there was little change in baseline or amphetamine-stimulated locomotor activity, employed as an indicator of dopaminergic hyperfunction. The temporally distinct behavioral effects of these PCP treatment regimes suggest that PPI deficits relate directly to acute NMDA receptor antagonism, whereas the more enduring set shifting deficits relate to the longer term consequences of NMDA receptor blockade. Therefore, these subchronic and chronic PCP treatment regimes produce hypofrontality (Cochran et al., Neuropsychopharmacology, 28:265-275, 2003) and associated prefrontal cortex-dependent deficits in behavioral flexibility which mirror core deficits in schizophrenia.

Differences in P50 and prepulse inhibition of the startle reflex between male smokers and non-smokers with first episode schizophrenia without medical treatment

Institute of Scientific and Technical Information of China (English)

Song Lisheng; Chen Xingshi; Chen Meijuan; Tang Yunxiang; Wang Jijun; Zhang Mingdao; Lou Feiying

2014-01-01

Backgorund Nicotine may improve schizophrenia patient's cognitive deficit symptoms.This study was to explore the chronic effects of smoking on prepulse inhibition of the startle reflex (PPI) and P50 in the patients with first-episode schizophrenia (FES).Methods The event-related potentials (ERP) recording and analysis instrument made by Brain Products,Germany,was used to detect PPI and P50 in 49 male FES patients (FES group,n=21 for smokers and n=28 for non-smokers) and 43 normal male controls (control group,n=19 for smokers and n=24 for non-smokers).Results Compared with normal controls,the FES group had prolonged PPI latency when elicited by single stronger stimulus (P ＜0.05); the FES group had prolonged PPI latency and increased PPI amplitude (P ＜0.05,0.01) when elicited by weak and strong stimuli.The FES group had lower PPI inhibition rate than normal controls (P ＜0.05).Compared with normal controls,the FES group had increased P50-S2 amplitude and increased amplitude ratio S2/S1 (both P ＜0.05).In the control group,the smokers had a tendency of increase in P50-S2 amplitude (P ＞0.05) and shorter P50-S2 latency (P ＜0.05) than the non-smokers.The smokers had higher PPI amplitude than the non-smokers (P ＜0.05).In the FES group,the smokers had higher P50-S1 amplitude,shorter P50-S2 latency,and higher amplitude ratio S2/S1 than the non-smokers (P ＜0.05,0.01).The smokers had higher PPI amplitude than the non-smokers (P ＜0.05).Conclusions There is obvious PPI and P50 deficits in schizophrenic patients.However,these deficits are relatively preserved in the smokers compared with the non-smokers,which suggests that long-term smoking might partially improve the sensory gating in schizophrenic patients.Whether this conclusion can be deduced to female patients requires further follow-ups.

Baclofen reverses the reduction in prepulse inhibition of the acoustic startle response induced by dizocilpine, but not by apomorphine.

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Bortolato, Marco; Frau, Roberto; Aru, Gian Nicola; Orrù, Marco; Gessa, Gian Luigi

2004-01-01

Since baclofen, the prototypical GABA(B) receptor agonist, is known to reduce the activity of dopaminergic mesolimbic neurons, a putative antipsychotic property of this compound has been suggested, but the evidence for this is still controversial. The aim of the present study was to elucidate the effects of baclofen on the prepulse inhibition (PPI) of the acoustic startle response (ASR), a behavioral paradigm considered to be one of the most powerful tools for the evaluation of sensorimotor gating and for the screening of antipsychotics. We tested the effects of baclofen (1.25, 2.5, 5 and 10 mg/kg IP) in rats, per se and in co-treatment with some of the substances known to induce a robust reduction of PPI, such as apomorphine (0.25 mg/kg SC) and dizocilpine (0.1 mg/kg SC). Finally, in order to ascertain whether the effects of baclofen could be ascribed to its activity on GABA(B) receptors, we analyzed whether its action could be prevented by pretreatment with SCH 50911, a selective GABA(B) receptor antagonist (20 mg/kg IP). All the experiments were carried out using standard procedures for the assessment of PPI of the ASR. Baclofen per se produced no significant change in PPI parameters. Moreover, while no effect on apomorphine-mediated alterations in PPI parameters was observed, baclofen proved able to reverse dizocilpine-induced PPI disruption, and this effect was significantly prevented by SCH 50911. On the other hand, this last compound exhibited no effects per se at the same dose. These results indicate that GABA(B) receptors are implicated in the neurobiological circuitry accounting for glutamatergic action in sensorimotor gating, and therefore can be proposed as putative new targets in the pharmacological therapy of psychotic disorders. Further studies should be addressed to evaluate more closely the clinical efficacy of baclofen in this respect.

The effects of the preferential 5-HT2A agonist psilocybin on prepulse inhibition of startle in healthy human volunteers depend on interstimulus interval.

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Vollenweider, Franz X; Csomor, Philipp A; Knappe, Bernhard; Geyer, Mark A; Quednow, Boris B

2007-09-01

Schizophrenia patients exhibit impairments in prepulse inhibition (PPI) of the startle response. Hallucinogenic 5-HT(2A) receptor agonists are used for animal models of schizophrenia because they mimic some symptoms of schizophrenia in humans and induce PPI deficits in animals. Nevertheless, one report indicates that the 5-HT(2A) receptor agonist psilocybin increases PPI in healthy humans. Hence, we investigated these inconsistent results by assessing the dose-dependent effects of psilocybin on PPI in healthy humans. Sixteen subjects each received placebo or 115, 215, and 315 microg/kg of psilocybin at 4-week intervals in a randomized and counterbalanced order. PPI at 30-, 60-, 120-, 240-, and 2000-ms interstimulus intervals (ISIs) was measured 90 and 165 min after drug intake, coinciding with the peak and post-peak effects of psilocybin. The effects of psilocybin on psychopathological core dimensions and sustained attention were assessed by the Altered States of Consciousness Rating Scale (5D-ASC) and the Frankfurt Attention Inventory (FAIR). Psilocybin dose-dependently reduced PPI at short (30 ms), had no effect at medium (60 ms), and increased PPI at long (120-2000 ms) ISIs, without affecting startle reactivity or habituation. Psilocybin dose-dependently impaired sustained attention and increased all 5D-ASC scores with exception of Auditory Alterations. Moreover, psilocybin-induced impairments in sustained attention performance were positively correlated with reduced PPI at the 30 ms ISI and not with the concomitant increases in PPI observed at long ISIs. These results confirm the psilocybin-induced increase in PPI at long ISIs and reveal that psilocybin also produces a decrease in PPI at short ISIs that is correlated with impaired attention and consistent with deficient PPI in schizophrenia.

Assessment of auditory sensory processing in a neurodevelopmental animal model of schizophrenia-Gating of auditory-evoked potentials and prepulse inhibition

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Broberg, Brian Villumsen; Oranje, Bob; Yding, Birte

2010-01-01

of sensory information processing seen in schizophrenia patients, can be assessed by highly homologues methods in both humans and rodents, evident by the prepulse inhibition (PPI) of the auditory startle response and the P50 (termed P1 here) suppression paradigms. Treatment with the NMDA receptor antagonist...... findings confirm measures of early information processing to show high resemblance between rodents and humans, and indicate that early postnatal PCP-treated rats show deficits in pre-attentional processing, which are distinct from those observed in schizophrenia patients.......The use of translational approaches to validate animal models is needed for the development of treatments that can effectively alleviate cognitive impairments associated with schizophrenia, which are unsuccessfully treated by the current available therapies. Deficits in pre-attentive stages...

Prepulse inhibition and facilitation of the postauricular reflex, a vestigial remnant of pinna startle.

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Hackley, Steven A; Ren, Xi; Underwood, Amy; Valle-Inclán, Fernando

2017-04-01

If the postauricular reflex (PAR) is to be used effectively in studies of emotion and attention, its sensitivity to basic modulatory effects such as prepulse inhibition and facilitation must be determined. Two experiments were carried out with healthy young adults to assess the effects of transient and sustained visual prestimuli on the pinna-flexion response to trains of startle probes. In the first experiment, participants passively viewed a small white square. It was displayed from 1,000 ms prior to onset of a train of noise bursts until the end of that train. Relative to no-prepulse control trials, PAR amplitude was inhibited, possibly due to the withdrawal of attentional resources from the auditory modality. In the second experiment, participants performed a visual oddball task in which irrelevant trains of startle probes followed most briefly displayed task stimuli (checkerboards). Prepulse inhibition was observed when a transient stimulus preceded the first probe at a lead time of 100 ms. Amplitude facilitation was observed at longer lead times. In addition to documenting the existence of prepulse inhibition and facilitation, the data suggest that the PAR is not elicited by visual stimuli, that temporal expectancy does not influence its amplitude or latency, and that this vestigial microreflex is resistant to habituation. Results are interpreted in light of a recent theory that the human PAR is a highly degraded pinna startle, in which the reflex arc no longer includes the startle center (nucleus reticularis pontis caudalis). © 2017 Society for Psychophysiological Research.

Effects of Cannabinoid Drugs on the Deficit of Prepulse Inhibition of Startle in an Animal Model of Schizophrenia: the SHR Strain

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Raquel eLevin

2014-02-01

Full Text Available Clinical and neurobiological findings suggest that the cannabinoids and the endocannabinoid system may be implicated in the pathophysiology and treatment of schizophrenia. We described that the Spontaneously Hypertensive Rats (SHR strain presents a schizophrenia behavioral phenotype that is specifically attenuated by antipsychotic drugs, and potentiated by proschizophrenia manipulations. Based on these findings, we have suggested this strain as an animal model of schizophrenia. The aim of this study was to evaluate the effects of cannabinoid drugs on the deficit of prepulse inhibition of startle (PPI, the main paradigm used to study sensorimotor gating impairment related to schizophrenia, presented by the SHR strain. The following drugs were used: 1 WIN55212,2 (cannabinoid agonist, 2 rimonabant (CB1 antagonist, 3 AM404 (anandamide uptake inhibitor, and 4 cannabidiol (indirect CB1/CB2 receptor antagonist, among other effects. Wistar rats (WR and SHRs were treated with vehicle or different doses of WIN55212 (0.3, 1 or 3 mg/kg, rimonabant (0.75, 1.5 or 3 mg/kg, AM404 (1, 5 or 10 mg/kg or cannabidiol (15, 30 or 60 mg/kg. Vehicle-treated SHRs showed a decreased PPI when compared to WRs. This PPI deficit was reversed by 1 mg/kg WIN and 30 mg/kg cannabidiol. Conversely, 0.75 mg/kg rimonabant decreased PPI in SHR strain, whereas AM404 did not modify it. Our results reinforce the role of the endocannabinoid system in the sensorimotor gating impairment related to schizophrenia, and point to cannabinoid drugs as potential therapeutic strategies.

High doses of salicylate causes prepulse facilitation of onset-gap induced acoustic startle response.

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Sun, Wei; Doolittle, Lauren; Flowers, Elizabeth; Zhang, Chao; Wang, Qiuju

2014-01-01

Prepulse inhibition of acoustic startle reflex (PPI), a well-established method for evaluating sensorimotor gating function, has been used to detect tinnitus in animal models. Reduced gap induced PPI (gap-PPI) was considered as a sign of tinnitus. The silent gap used in the test contains both onset and offset signals. Tinnitus may affect these cues differently. In this experiment, we studied the effects of a high dose of salicylate (250 mg/kg, i.p.), an inducer of reversible tinnitus and sensorineural hearing loss, on gap-PPI induced by three different gaps: an onset-gap with 0.1 ms onset and 25 ms offset time, an offset-gap with 25 ms onset and 0.1 ms offset time, and an onset-offset-gap with 0.1 ms onset and offset time. We found that the onset-gaps induced smaller inhibitions than the offset-gaps before salicylate treatment. The offset-gap induced PPI was significantly reduced 1-3h after salicylate treatment. However, the onset-gap caused a facilitation of startle response. These results suggest that salicylate induced reduction of gap-PPI was not only caused by the decrease of offset-gap induced PPI, but also by the facilitation induced by the onset-gap. Since the onset-gap induced PPI is caused by neural offset response, our results suggest that salicylate may cause a facilitation of neural response to an offset acoustical signal. Treatment of vigabatrin (60 mg/kg/day, 14 days), which elevates the GABA level in the brain, blocked the offset-gap induced PPI and onset-gap induced facilitation caused by salicylate. These results suggest that enhancing GABAergic activities can alleviate salicylate induced tinnitus. Published by Elsevier B.V.

Repeated forced swimming impairs prepulse inhibition and alters brain-derived neurotrophic factor and astroglial parameters in rats.

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Borsoi, Milene; Antonio, Camila Boque; Müller, Liz Girardi; Viana, Alice Fialho; Hertzfeldt, Vivian; Lunardi, Paula Santana; Zanotto, Caroline; Nardin, Patrícia; Ravazzolo, Ana Paula; Rates, Stela Maris Kuze; Gonçalves, Carlos-Alberto

2015-01-01

Glutamate perturbations and altered neurotrophin levels have been strongly associated with the neurobiology of neuropsychiatric disorders. Environmental stress is a risk factor for mood disorders, disrupting glutamatergic activity in astrocytes in addition to cognitive behaviours. Despite the negative impact of stress-induced neuropsychiatric disorders on public health, the molecular mechanisms underlying the response of the brain to stress has yet to be fully elucidated. Exposure to repeated swimming has proven useful for evaluating the loss of cognitive function after pharmacological and behavioural interventions, but its effect on glutamate function has yet to be fully explored. In the present study, rats previously exposed to repeated forced swimming were evaluated using the novel object recognition test, object location test and prepulse inhibition (PPI) test. In addition, quantification of brain-derived neurotrophic factor (BDNF) mRNA expression and protein levels, glutamate uptake, glutathione, S100B, GluN1 subunit of N-methyl-D-aspartate receptor and calmodulin were evaluated in the frontal cortex and hippocampus after various swimming time points. We found that swimming stress selectively impaired PPI but did not affect memory recognition. Swimming stress altered the frontal cortical and hippocampal BDNF expression and the activity of hippocampal astrocytes by reducing hippocampal glutamate uptake and enhancing glutathione content in a time-dependent manner. In conclusion, these data support the assumption that astrocytes may regulate the activity of brain structures related to cognition in a manner that alters complex behaviours. Moreover, they provide new insight regarding the dynamics immediately after an aversive experience, such as after behavioural despair induction, and suggest that forced swimming can be employed to study altered glutamatergic activity and PPI disruption in rodents. Copyright © 2014. Published by Elsevier Inc.

The effects of methylphenidate on prepulse inhibition during attended and ignored prestimuli among boys with attention-deficit hyperactivity disorder.

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Hawk, Larry W; Yartz, Andrew R; Pelham, William E; Lock, Thomas M

2003-01-01

The present study investigated attentional modification of prepulse inhibition of startle among boys with and without attention-deficit hyperactivity disorder (ADHD). Two hypotheses were tested: (1) whether ADHD is associated with diminished prepulse inhibition during attended prestimuli, but not ignored prestimuli, and (2) whether methylphenidate selectively increases prepulse inhibition to attended prestimuli among boys with ADHD. Participants were 17 boys with ADHD and 14 controls. Participants completed a tone discrimination task in each of two sessions separated by 1 week. ADHD boys were administered methylphenidate (0.3 mg/kg) in one session and placebo in the other session in a randomized, double-blind fashion. During each series of 72 tones (75 dB; half 1200-Hz, half 400-Hz), participants were paid to attend to one pitch and ignore the other. Bilateral eyeblink electromyogram startle responses were recorded in response to acoustic probes (50-ms, 102-dB white noise) presented following the onset of two-thirds of tones, and during one-third of intertrial intervals. Relative to controls, boys with ADHD exhibited diminished prepulse inhibition 120 ms after onset of attended but not ignored prestimuli following placebo administration. Methylphenidate selectively increased prepulse inhibition to attended prestimuli at 120 ms among boys with ADHD to a level comparable to that of controls, who did not receive methylphenidate. These data are consistent with the hypothesis that ADHD involves diminished selective attention and suggest that methylphenidate ameliorates the symptoms of ADHD, at least in part, by altering an early attentional mechanism.

A New Statistical Approach for the Evaluation of Gap-prepulse Inhibition of the Acoustic Startle Reflex (GPIAS for Tinnitus Assessment

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Achim Schilling

2017-10-01

Full Text Available Background: An increasingly used behavioral paradigm for the objective assessment of a possible tinnitus percept in animal models has been proposed by Turner and coworkers in 2006. It is based on gap-prepulse inhibition (PPI of the acoustic startle reflex (ASR and usually referred to as GPIAS. As it does not require conditioning it became the method of choice to study neuroplastic phenomena associated with the development of tinnitus.Objective: It is still controversial if GPIAS is really appropriate for tinnitus screening, as the hypothesis that a tinnitus percept impairs the gap detection ability (“filling-in interpretation” is still questioned. Furthermore, a wide range of criteria for positive tinnitus detection in GPIAS have been used across different laboratories and there still is no consensus on a best practice for statistical evaluation of GPIAS results. Current approaches are often based on simple averaging of measured PPI values and comparisons on a population level without the possibility to perform valid statistics on the level of the single animal.Methods: A total number of 32 animals were measured using the standard GPIAS paradigm with varying number of measurement repetitions. Based on this data further statistical considerations were performed.Results: We here present a new statistical approach to overcome the methodological limitations of GPIAS. In a first step we show that ASR amplitudes are not normally distributed. Next we estimate the distribution of the measured PPI values by exploiting the full combinatorial power of all measured ASR amplitudes. We demonstrate that the amplitude ratios (1-PPI are approximately lognormally distributed, allowing for parametrical testing of the logarithmized values and present a new statistical approach allowing for a valid and reliable statistical assessment of PPI changes in GPIAS.Conclusion: Based on our statistical approach we recommend using a constant criterion, which does not

Inhibition of somatosensory-evoked cortical responses by a weak leading stimulus.

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Nakagawa, Kei; Inui, Koji; Yuge, Louis; Kakigi, Ryusuke

2014-11-01

We previously demonstrated that auditory-evoked cortical responses were suppressed by a weak leading stimulus in a manner similar to the prepulse inhibition (PPI) of startle reflexes. The purpose of the present study was to investigate whether a similar phenomenon was present in the somatosensory system, and also whether this suppression reflected an inhibitory process. We recorded somatosensory-evoked magnetic fields following stimulation of the median nerve and evaluated the extent by which they were suppressed by inserting leading stimuli at an intensity of 2.5-, 1.5-, 1.1-, or 0.9-fold the sensory threshold (ST) in healthy participants (Experiment 1). The results obtained demonstrated that activity in the secondary somatosensory cortex in the hemisphere contralateral to the stimulated side (cSII) was significantly suppressed by a weak leading stimulus with the intensity larger than 1.1-fold ST. This result implied that the somatosensory system had an inhibitory process similar to that of PPI. We then presented two successive leading stimuli before the test stimulus, and compared the extent of suppression between the test stimulus-evoked responses and those obtained with the second prepulse alone and with two prepulses (first and second) (Experiment 2). When two prepulses were preceded, cSII responses to the second prepulse were suppressed by the first prepulse, whereas the ability of the second prepulse to suppress the test stimulus remained unchanged. These results suggested the presence of at least two individual pathways; response-generating and inhibitory pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of combined exposure to pyridostigmine bromide and shaker stress on acoustic startle response, pre-pulse inhibition and open field behavior in mice.

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Dubovicky, M; Paton, S; Morris, M; Mach, M; Lucot, J B

2007-01-01

The present study investigated the effect of combined exposure of pyridostigmine bromide (PB) and chronic shaker stress on acoustic startle responses (ASR), pre-pulse inhibition (PPI) and open field behavior of adult C57BL/6J mice. PB (10 mg kg(-1) day(-1) for 7 days) or saline was administered subcutaneously using osmotic Alzet minipumps implanted under the skin on the back of the mice. At the same time, the mice were exposed to 7 days of intermittent shaker stress. They were tested for ASR (100 dB and 120 dB stimuli) and PPI (70 dB + 100 dB and 70 dB + 120 dB) in the acoustic startle monitor system. The mice were assessed during the shaker stress on days 2 and 7 and 7, 14, 21 and 28 days after discontinuation of treatment. Separate groups of mice were tested in the open field in 15 min sessions on days 1, 3 and 6 during shaker stress and PB treatment. Exposure of mice to PB resulted in an exaggerated ASR, reduced PPI and non-significant decrease in locomotor activity. These behavioral changes were apparent only during exposure to PB. Repeated shaker stress did not have any effect on sensorimotor functions or open field behavior of mice. There was no prolonged or delayed effect of PB and/or stress on individual behavioral variables. The study found C57BL/6J mice to be behaviorally sensitive to PB treatment. (c) 2007 John Wiley & Sons, Ltd.

White matter hyperintensities and prepulse inhibition in a mixed elderly population

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Salem, Lise C; Hejl, Anne-Mette; Garde, Ellen

2011-01-01

resonance imaging (MRI) in elderly subjects with and without cognitive impairment, may contribute to variations in PPI. A passive acoustic PPI paradigm was applied in 92 human subjects (53 healthy and 39 patients with Alzheimer's disease or mild cognitive impairment) between 60 and 85years of age. WMH were...... rated visually on craniel MRI FLAIR images using the Fazekas scale. WMH were identified in 70% of all subjects. The latency to peak of the startle response increased significantly with increasing WMH load, whereas the inhibition of the startle response (PPI) was neither significantly related...... to the degree of WMH nor to cognitive performance. We conclude that the presence of WMH in the fronto-striatal brain circuit may affect the latency of the startle response, but not information processing in elderly subjects....

Neuroligin 2 R215H Mutant Mice Manifest Anxiety, Increased Prepulse Inhibition, and Impaired Spatial Learning and Memory

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Chia-Hsiang Chen

2017-11-01

Full Text Available Neuroligin 2 (NLGN2 is a postsynaptic adhesion protein that plays an essential role in synaptogenesis and function of inhibitory neuron. We previously identified a missense mutation R215H of the NLGN2 in a patient with schizophrenia. This missense mutation was shown to be pathogenic in several cell-based assays. The objective of this study was to better understand the behavioral consequences of this mutation in vivo. We generated a line of transgenic mice carrying this mutation using a recombinant-based method. The mice were subjected to a battery of behavioral tests including open field locomotor activity assay, prepulse inhibition (PPI assay, accelerated rotarod test, novel location and novel recognition tests, elevated plus-maze (EPM test, and Morris water maze test. The transgenic animals were viable and fertile, but the Nlgn2 R215H knock-in (KI homozygous mice showed growth retardation, anxiety-like behavior, increased PPI, and impaired spatial learning and memory. There was no significant interaction between sex and genotype in most behavioral tests; however, we observed a significant interaction between sex and genotype in EPM test in this study. Also, we found that the Nlgn2 R215H homozygous KI mice did not express the NLGN2 protein, resembling Nlgn2 knockout mice. Our results demonstrate that Nlgn2 R215H KI homozygous mice manifest several behavioral abnormalities similar to those found in psychiatric patients carrying NLGN2 mutations, indicating that dysfunction of NLGN2 contributes to the pathogenesis of certain psychiatric symptoms commonly present in various mental disorders, not limited to schizophrenia.

An investigation into ‘two hit’ effects of BDNF deficiency and young-adult cannabinoid receptor stimulation on prepulse inhibition regulation and memory in mice

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Maren eKlug

2013-10-01

Full Text Available Reduced brain-derived neurotrophic factor (BDNF signalling has been shown in the frontal cortex and hippocampus in schizophrenia. The aim of the present study was to investigate whether a BDNF deficit would modulate effects of chronic cannabis intake, a well-described risk factor for schizophrenia development. BDNF heterozygous mice (HET and wild-type controls were chronically treated during weeks 6, 7 and 8 of life with the cannabinoid CB1 receptor agonist, CP55,940 (CP. After a 2-week delay, there were no CP-induced deficits in any of the groups in short-term spatial memory in a Y-maze task or novel object recognition memory. Baseline prepulse inhibition (PPI was lower but average startle was increased in BDNF HET compared to wild-type controls. Acute CP administration before the PPI session caused a marked increase in PPI in male HET mice pre-treated with CP but not in any of the other male groups. In females, there were small increases of PPI in all groups upon acute CP administration. Acute CP administration furthermore reduced startle and this effect was greater in HET mice irrespective of chronic CP pre-treatment. Analysis of the levels of [3H]CP55,940 binding by autoradiography revealed a significant increase in the nucleus accumbens of male BDNF HET mice previously treated with CP but not in any of the other groups or in the caudate nucleus.These results show that BDNF deficiency and chronic young-adult cannabinoid receptor stimulation do not interact in this model on learning and memory later in life. In contrast, male ‘two hit’ mice, but not females, were hypersensitive to the effect of acute CP on sensorimotor gating. These effects may be related to a selective increase of [3H]CP55,940 binding in the nucleus accumbens, reflecting up-regulation of CB1 receptor density in this region. These data could be of relevance to our understanding of differential ‘two hit’ neurodevelopmental mechanisms in schizophrenia.

Prepulse suppression and allowable prepulse voltage in Z-pinch experiments

International Nuclear Information System (INIS)

Xia Minghe; Xie Weiping; Li Hongtao

2004-01-01

The causes of prepulse origin in pulse power machine especially in Blumlein pulser are analyzed in this paper. A method that can reduce the prepulse by an inductance between Marx and zero voltage node has been presented while a calculation example used Pspice is provided. The prepulse switches can be used to reduce the prepulse effects in many fields. The prepulse requests for wire arrays in Z-pinch experiments are analyzed and explained by means of specific reaction quantity and vaporization heat, the results of the calculations are similar. In fact, the results of experiments indicate that the energy deposited in the wires is sufficient to bring the aluminium wires to partial or total vaporization. Because the value of prepulse current is larger than that of calculation, this indicates the calculation method is right

Structural brain correlates of sensorimotor gating in antipsychotic-naive men with first-episode schizophrenia

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Hammer, Trine B; Oranje, Bob; Skimminge, Arnold

2013-01-01

in the left rostral dorsal premotor cortex, the right presupplementary motor area and the anterior medial superior frontal gyrus bilaterally. Follow-up analyses suggested that the rostral dorsal premotor cortex and presupplementary motor area correlations were driven predominantly by the controls. Limitations......Background: Prepulse inhibition (PPI) of the startle reflex is modulated by a complex neural network. Prepulse inhibition impairments are found at all stages of schizophrenia. Previous magnetic resonance imaging (MRI) studies suggest that brain correlates of PPI differ between patients...... with schizophrenia and healthy controls; however, these studies included only patients with chronic illness and medicated patients. Our aim was to examine the structural brain correlates of PPI in antipsychotic-naive patients with first-episode schizophrenia. Methods: We performed acoustic PPI assessment...

Investigation of the effects of head irradiation with gamma rays and protons on startle and pre-pulse inhibition behavior in mice.

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Haerich, Paul; Eggers, Cara; Pecaut, Michael J

2012-05-01

With the increased international emphasis on manned space exploration, there is a growing need to understand the impact of the spaceflight environment on health and behavior. One particularly important aspect of this environment is low-dose radiation. In the present studies, we first characterized the γ- and proton-irradiation dose effect on acoustic startle and pre-pulse inhibition behaviors in mice exposed to 0-5 Gy brain-localized irradiation, and assessed these effects 2 days later. Subsequently, we used 2 Gy to assess the time course of γ- and proton-radiation effects on startle reactivity 0-8 days after exposure. Exposures targeted the brain to minimize the impact of peripheral inflammation-induced sickness behavior. The effects of radiation on startle were subtle and acute. Radiation reduced the startle response at 2 and 5 Gy. Following a 2-Gy exposure, the response reached a minimum at the 2-day point. Proton and γ-ray exposures did not differ in their impact on startle. We found there were no effects of radiation on pre-pulse inhibition of the startle response.

Interaction of reelin and stress on immobility in the forced swim test but not dopamine-mediated locomotor hyperactivity or prepulse inhibition disruption: Relevance to psychotic and mood disorders.

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Notaras, Michael J; Vivian, Billie; Wilson, Carey; van den Buuse, Maarten

2017-07-13

Psychotic disorders, such as schizophrenia, as well as some mood disorders, such as bipolar disorder, have been suggested to share common biological risk factors. One such factor is reelin, a large extracellular matrix glycoprotein that regulates neuronal migration during development as well as numerous activity-dependent processes in the adult brain. The current study sought to evaluate whether a history of stress exposure interacts with endogenous reelin levels to modify behavioural endophenotypes of relevance to psychotic and mood disorders. Heterozygous Reeler Mice (HRM) and wildtype (WT) controls were treated with 50mg/L of corticosterone (CORT) in their drinking water from 6 to 9weeks of age, before undergoing behavioural testing in adulthood. We assessed methamphetamine-induced locomotor hyperactivity, prepulse inhibition (PPI) of acoustic startle, short-term spatial memory in the Y-maze, and depression-like behaviour in the Forced-Swim Test (FST). HRM genotype or CORT treatment did not affect methamphetamine-induced locomotor hyperactivity, a model of psychosis-like behaviour. At baseline, HRM showed decreased PPI at the commonly used 100msec interstimulus interval (ISI), but not at the 30msec ISI or following challenge with apomorphine. A history of CORT exposure potentiated immobility in the FST amongst HRM, but not WT mice. In the Y-maze, chronic CORT treatment decreased novel arm preference amongst HRM, reflecting reduced short-term spatial memory. These data confirm a significant role of endogenous reelin levels on stress-related behaviour, supporting a possible role in both bipolar disorder and schizophrenia. However, an interaction of reelin deficiency with dopaminergic regulation of psychosis-like behaviour remains unclear. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessing the Comprehensive Soldier Fitness Program: Measuring Startle Response and Prepulse Inhibition

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2011-04-01

increase PPI, but dopamine agonists can have the opposite effect by reducing PPI. Fortunately, caffeine appears to have no significant effect on PPI...violent behavior, and sexual risk behavior. Landis, C., & Hunt, W.A. (1939). The Startle Pattern. New York: Farrar. An example of early research on

Inhibition in Parkinson’s disease: A focus on prepulse inhibition and Rapid eye movement sleep Behavior Disorder (RBD)

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Zoetmulder, Marielle

2014-01-01

Summary Background: α-synucleinopathies are characterized by degeneration of the nigrostriatal pathway and midbrain dopamine function. These disorders, including Parkinson’s disease (PD), are associated with sensorimotor gating deficits and show an increased prevalence of the parasomnia REM sleep...... with daytime motor function in Parkinsonism, the relation to the increased motor activity during REM sleep as seen in RBD is unclear. Aim: The objective of this thesis was 1) to examine prepulse inhibition of the acoustic blink reflex in patients with idiopathic REM sleep behaviour disorder (iRBD), Parkinson...... in the striatum. Moreover, our results support the hypothesis that increased EMG-activity during REM sleep in iRBD is associated with the nigrostriatal dopamine system, while EMG-activity during REM-sleep in PD is associated with dopaminergic medication....

Neural correlates of sensorimotor gating: A metabolic positron emission tomography study in awake rats

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Cathrin eRohleder

2014-05-01

Full Text Available Impaired sensorimotor gating occurs in neuropsychiatric disorders such as schizophrenia and can be measured using the prepulse inhibition (PPI paradigm of the acoustic startle response. This assay is frequently used to validate animal models of neuropsychiatric disorders and to explore the therapeutic potential of new drugs. The underlying neural network of PPI has been extensively studied with invasive methods and genetic modifications. However, its relevance for healthy untreated animals and the functional interplay between startle- and PPI-related areas during a PPI session is so far unknown. Therefore, we studied awake rats in a PPI paradigm, startle control and background noise control, combined with behavioral [18F]fluoro-2-deoxyglucose positron emission tomography (FDG-PET. Subtractive analyses between conditions were used to identify brain regions involved in startle and PPI processing in well-hearing Black hooded rats. For correlative analysis with regard to the amount of PPI we also included hearing-impaired Lister hooded rats that startled more often, because their hearing threshold was just below the lowest prepulses. Metabolic imaging showed that the brain areas proposed for startle and PPI mediation are active during PPI paradigms in healthy untreated rats. More importantly, we show for the first time that the whole PPI modulation network is active during passive PPI sessions, where no selective attention to prepulse or startle stimulus is required. We conclude that this reflects ongoing monitoring of stimulus significance and constant adjustment of sensorimotor gating.

Brief Report: Sensorimotor Gating in Idiopathic Autism and Autism Associated with Fragile X Syndrome

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Yuhas, Jennifer; Cordeiro, Lisa; Tassone, Flora; Ballinger, Elizabeth; Schneider, Andrea; Long, James M.; Ornitz, Edward M.; Hessl, David

2011-01-01

Prepulse inhibition (PPI) may useful for exploring the proposed shared neurobiology between idiopathic autism and autism caused by FXS. We compared PPI in four groups: typically developing controls (n = 18), FXS and autism (FXS+A; n = 15), FXS without autism spectrum disorder (FXS-A; n = 17), and idiopathic autism (IA; n = 15). Relative to…

Methodological optimization of tinnitus assessment using prepulse inhibition of the acoustic startle reflex.

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Longenecker, R J; Galazyuk, A V

2012-11-16

Recently prepulse inhibition of the acoustic startle reflex (ASR) became a popular technique for tinnitus assessment in laboratory animals. This method confers a significant advantage over the previously used time-consuming behavioral approaches utilizing basic mechanisms of conditioning. Although this technique has been successfully used to assess tinnitus in different laboratory animals, many of the finer details of this methodology have not been described enough to be replicated, but are critical for tinnitus assessment. Here we provide detail description of key procedures and methodological issues that provide guidance for newcomers with the process of learning to correctly apply gap detection techniques for tinnitus assessment in laboratory animals. The major categories of these issues include: refinement of hardware for best performance, optimization of stimulus parameters, behavioral considerations, and identification of optimal strategies for data analysis. This article is part of a Special Issue entitled: Tinnitus Neuroscience. Copyright © 2012. Published by Elsevier B.V.

Inhibition of 5a-reductase in the nucleus accumbens counters sensorimotor gating deficits induced by dopaminergic activation

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Devoto, Paola; Frau, Roberto; Bini, Valentina; Pillolla, Giuliano; Saba, Pierluigi; Flore, Giovanna; Corona, Marta; Marrosu, Francesco; Bortolato, Marco

2012-01-01

Summary Cogent evidence highlights a key role of neurosteroids and androgens in schizophrenia. We recently reported that inhibition of steroid 5α-reductase (5αR), the rate-limiting enzyme in neurosteroid synthesis and androgen metabolism, elicits antipsychotic-like effects in humans and animal models, without inducing extrapyramidal side effects. To elucidate the anatomical substrates mediating these effects, we investigated the contribution of peripheral and neural structures to the behavioral effects of the 5αR inhibitor finasteride (FIN) on the prepulse inhibition (PPI) of the acoustic startle reflex (ASR), a rat paradigm that dependably simulates the sensorimotor gating impairments observed in schizophrenia and other neuropsychiatric disorders. The potential effect of drug-induced ASR modifications on PPI was excluded by measuring this index both as percent (%PPI) and absolute values (ΔPPI). In both orchidectomized and sham-operated rats, FIN prevented the %PPI deficits induced by the dopamine (DA) receptor agonists apomorphine (APO, 0.25 mg/kg, SC) and d-amphetamine (AMPH, 2.5 mg/kg, SC), although the latter effect was not corroborated by ΔPPI analysis. Conversely, APO-induced PPI deficits were countered by FIN infusions in the brain ventricles (10 μg/1 μl) and in the nucleus accumbens (NAc) shell and core (0.5 μg/0.5 μl/side). No significant PPI-ameliorating effect was observed following FIN injections in other brain regions, including dorsal caudate, basolateral amygdala, ventral hippocampus and medial prefrontal cortex, although a statistical trend was observed for the latter region. The efflux of DA in NAc was increased by systemic, but not intracerebral FIN administration. Taken together, these findings suggest that the role of 5αR in gating regulation is based on post-synaptic mechanisms in the NAc, and is not directly related to alterations in DA efflux in this region. PMID:22029952

Ultrasonic vocalizations, predictability and sensorimotor gating in the rat.

Science.gov (United States)

Webber, Emily S; Mankin, David E; McGraw, Justin J; Beckwith, Travis J; Cromwell, Howard C

2013-09-15

Prepulse inhibition (PPI) is a measure of sensorimotor gating in diverse groups of animals including humans. Emotional states can influence PPI in humans both in typical subjects and in individuals with mental illness. Little is known about emotional regulation during PPI in rodents. We used ultrasonic vocalization recording to monitor emotional states in rats during PPI testing. We altered the predictability of the PPI trials to examine any alterations in gating and emotional regulation. We also examined PPI in animals selectively bred for high or low levels of 50kHz USV emission. Rats emitted high levels of 22kHz calls consistently throughout the PPI session. USVs were sensitive to prepulses during the PPI session similar to startle. USV rate was sensitive to predictability among the different levels tested and across repeated experiences. Startle and inhibition of startle were not affected by predictability in a similar manner. No significant differences for PPI or startle were found related to the different levels of predictability; however, there was a reduction in USV signals and an enhancement of PPI after repeated exposure. Animals selectively bred to emit high levels of USVs emitted significantly higher levels of USVs during the PPI session and a reduced ASR compared to the low and random selective lines. Overall, the results support the idea that PPI tests in rodents induce high levels of negative affect and that manipulating emotional styles of the animals alters the negative impact of the gating session as well as the intensity of the startle response. Copyright © 2013 Elsevier B.V. All rights reserved.

Sensorimotor gating deficits in multiple system atrophy

DEFF Research Database (Denmark)

Zoetmulder, Marielle; Biernat, Heidi Bryde; Nikolic, Miki

2014-01-01

Prepulse inhibition (PPI) of the auditory blink reflex is a measure of sensorimotor gating, which reflects an organism's ability to filter out irrelevant sensory information. PPI has never been studied in patients with multiple system atrophy (MSA), although sensorimotor deficits are frequently a...... associated with synucleinopathies. We investigated whether alterations in PPI were more pronounced in MSA compared with Parkinson's disease (PD), idiopathic rapid eye movement sleep behavior disorder (iRBD) and healthy controls....

GluN2C/GluN2D subunit-selective NMDA receptor potentiator CIQ reverses MK-801-induced impairment in prepulse inhibition and working memory in Y-maze test in mice

Science.gov (United States)

Suryavanshi, P S; Ugale, R R; Yilmazer-Hanke, D; Stairs, D J; Dravid, S M

2014-01-01

Background and Purpose Despite ample evidence supporting the N-methyl-d-aspartate receptor (NMDAR) hypofunction hypothesis of schizophrenia, progress in the development of effective therapeutics based on this hypothesis has been limited. Facilitation of NMDA receptor function by co-agonists (d-serine or glycine) only partially alleviates the symptoms in schizophrenia; other means to facilitate NMDA receptors are required. NMDA receptor sub-types differ in their subunit composition, with varied GluN2 subunits (GluN2A-GluN2D) imparting different physiological, biochemical and pharmacological properties. CIQ is a positive allosteric modulator that is selective for GluN2C/GluN2D-containing NMDA receptors (Mullasseril et al.). Experimental Approach The effect of systemic administration of CIQ was tested on impairment in prepulse inhibition (PPI), hyperlocomotion and stereotypy induced by i.p. administration of MK-801 and methamphetamine. The effect of CIQ was also tested on MK-801-induced impairment in working memory in Y-maze spontaneous alternation test. Key Results We found that systemic administration of CIQ (20 mg·kg−1, i.p.) in mice reversed MK-801 (0.15 mg·kg−1, i.p.)-induced, but not methamphetamine (3 mg·kg−1, i.p.)-induced, deficit in PPI. MK-801 increased the startle amplitude to pulse alone, which was not reversed by CIQ. In contrast, methamphetamine reduced the startle amplitude to pulse alone, which was reversed by CIQ. CIQ also partially attenuated MK-801- and methamphetamine-induced hyperlocomotion and stereotyped behaviours. Additionally, CIQ reversed the MK-801-induced working memory deficit in spontaneous alternation in a Y-maze. Conclusion and Implications Together, these results suggest that facilitation of GluN2C/GluN2D-containing receptors may serve as an important therapeutic strategy for treating positive and cognitive symptoms in schizophrenia. PMID:24236947

Measurements of low-level prepulse on Nike KrF laser

International Nuclear Information System (INIS)

Karasik, Max; Mostovych, A.N.; Lehmberg, R.H.; Chan, Y.; Weaver, J.L.; Obenschain, S.P.

2005-01-01

The krypton fluoride (KrF) laser is a leading candidate driver for inertial fusion energy. Some of the current fusion target designs call for targets with thin metallic coatings. These targets could be particularly susceptible to preheat by a low-level laser prepulse. Knowledge of the prepulse can be important in understanding and modeling the behavior of such targets. This paper presents measurements of low-level prepulse on target with the Nike KrF laser. Sources of prepulse are discussed and measurements are performed under several specific laser conditions in order to evaluate the relative contribution of these sources to the overall prepulse. Prepulse is found to be ∼2x10 -7 from peak intensity for approximately 120 ns prior to the main laser pulse. Prepulse energy density on target is ∼2 J/cm 2 . The first laser amplifier in the time- and angle-multiplexed section of the laser is found to be the dominant source of prepulse

Effects of Dopamine D2/D3 Blockade on Human Sensory and Sensorimotor Gating in Initially Antipsychotic-Naive, First-Episode Schizophrenia Patients

DEFF Research Database (Denmark)

Düring, Signe; Glenthøj, Birte Y; Andersen, Gitte Saltoft

2014-01-01

It has been suggested that psychophysiological measures of sensory and sensorimotor gating, P50 gating and prepulse inhibition of the startle reflex (PPI), underlie core features of schizophrenia and are linked to dopaminergic pathways in the striatum and prefrontal cortex. In the present study, ...

Sensorimotor gating and habituation in antipsychotic-naive, first-episode schizophrenia patients before and after 6 months' treatment with quetiapine

DEFF Research Database (Denmark)

Aggernaes, Bodil; Glenthøj, Birte Yding; Ebdrup, Bjorn H

2010-01-01

Impaired prepulse inhibition of the startle reflex (PPI) in schizophrenia has been replicated in many studies. However, previous results may have been influenced by course of illness, and antipsychotic medication. Studies on antipsychotic-naive, first-episode schizophrenia patients are lacking....... Treatment with quetiapine for 6 months increased male PPI to a level where it was no longer statistically different from the controls. The much smaller group of females did not show PPI deficits at baseline. In addition, compared to controls, patients appeared highly aroused and showed a strong yet non...

Disruption in a Neurodevelopmental Model of Schizophrenia

Directory of Open Access Journals (Sweden)

Benjamin Rolland

2012-01-01

Full Text Available Oxidative stress has been implicated in neurodevelopmental theories of schizophrenia. Antioxidant Peroxysome Proliferator-Activated Receptors α (PPARα agonist fenofibrate has neuroprotective properties and could reverse early preclinical infringements that could trigger the illness. We have evaluated the neuroprotective interest of fenofibrate in a neurodevelopmental rat model of schizophrenia. The oxidative lesion induced by Kainic Acid (KA injection at postnatal day (PND 7 has previously been reported to disrupt Prepulse Inhibition (PPI at PND56 but not at PND35. In 4 groups of 15 male rats each, KN (KA-PND7 + normal postweaning food, KF (KA-PND7 + fenofibrate 0.2% food, ON (saline-PND7 + normal food, and OF (saline + fenofibrate food, PPI was recorded at PND35 and PND56. Three levels of prepulse were used: 73 dB, 76 dB, and 82 dB for a pulse at 120 dB. Four PPI scores were analyzed: PPI73, PPI76, PPI82, and mean PPI (PPIm. Two-way ANOVAs were used to evaluate the effects of both factors (KA + fenofibrate, and, in case of significant results, intergroup Student’s t-tests were performed. We notably found a significant difference (P<0.05 in PPIm between groups KN and KF at PND56, which supposes that fenofibrate could be worthy of interest for early neuroprotection in schizophrenia.

Mice lacking collapsin response mediator protein 1 manifest hyperactivity, impaired learning and memory, and impaired prepulse inhibition

Directory of Open Access Journals (Sweden)

Naoya eYamashita

2013-12-01

Full Text Available Collapsin response mediator protein 1 (CRMP1 is one of the CRMP family members that are involved in various aspects of neuronal development such as axonal guidance and neuronal migration. Here we provide evidence that crmp1-/- mice exhibited behavioral abnormalities related to schizophrenia. The crmp1-/- mice exhibited hyperactivity and/or impaired emotional behavioral phenotype. These mice also exhibited impaired context-dependent memory and long-term memory retention. Furthermore, crmp1-/- mice exhibited decreased prepulse inhibition, and this phenotype was rescued by administration of chlorpromazine, a typical antipsychotic drug. In addition, in vivo microdialysis revealed that the methamphetamine-induced release of dopamine in prefrontal cortex was exaggerated in crmp1-/- mice, suggesting that enhanced mesocortical dopaminergic transmission contributes to their hyperactivity phenotype. These observations suggest that impairment of CRMP1 function may be involved in the pathogenesis of schizophrenia. We propose that crmp1-/- mouse may model endophenotypes present in this neuropsychiatric disorder.

Gestational chronic mild stress: Effects on acoustic startle in male offspring of rats

DEFF Research Database (Denmark)

Hougaard, K.S.; Mandrup, Karen; Kjaer, S.L.

2011-01-01

An increasing number of scientific studies indicate that maternal stress during pregnancy influences fetal development of the nervous system and thereby the behavioural phenotype. We have previously reported attenuated prepulse inhibition (PPI) of the startle reaction in adult female rats derived...... paradigm of stressors affected the PPI response pattern in male rats. In prenatally manipulated males, the PPI response differed statistically significantly, depending on prior exposure to an episode of postnatal acute stress (blood sampling under restraint). In contrast, the PPI response in control males...... was unaffected by this postnatal experience. The present work supports the hypothesis that the maternal environment is a long-term determinant of phenotypic differences in sensitivity to stressors....

Evaluation of the effect of prepulses on HF laser-target interactions

International Nuclear Information System (INIS)

Matzen, M.K.

1979-06-01

We have assessed the effect of multinanosecond, low-power-density prepulses on the interaction of multinanosecond, 10 14 W/cm 2 , approx. 3 -μm HF laser pulses with slab targets. The emphasis is on analyzing absorption and x-ray conversion efficiency. A survey of previous experiments gives no evidence that these prepulses will affect the total absorption. However, prepulses have been observed to cause qualitative changes in both the x-ray spectrum and conversion efficiency. Numerical simulations indicate that the laser-target interaction is effectively insensitive to low-power-density prepulses. These studies imply that basic laser-target experiments with multiplexed, HF laser pulses will provide an important characterization of the interaction of long pulse, multi-line, approx. 3 μm radiation with targets. Future wavelength comparison experiments will require prepulse suppression or target isolation

Sensorimotor gating impairments induced by MK-801 treatment may be reduced by tolerance effect and by familiarization in monkeys

Science.gov (United States)

Saletti, Patricia G.; Maior, Rafael S.; Hori, Etsuro; Nishijo, Hisao; Tomaz, Carlos

2015-01-01

Dizocilpine (MK-801) is a non-competitive NMDA antagonist that induces schizophreniclike effects. It is therefore widely used in experimental models of schizophrenia including prepulse inhibition (PPI) impairments in rodents. Nevertheless, MK-801 has never been tested in monkeys on a PPI paradigm. In order to evaluate MK-801 effects on monkeys’ PPI, we tested eight capuchin monkeys (Sapajus spp.) using three different doses of MK-801 (0.01; 0.02; 0.03 mg/kg). Results show PPI impairment in acute administration of the highest dose (0.03 mg/kg). PPI impairment induced by MK-801 was reversed by re-exposure to the PPI test throughout treatment trials, in contrast with rodent studies. These results indicate that tolerance effect and familiarization with PPI test may reduce the sensorimotor gating deficits induced by MK-801 in monkeys, suggesting a drug-training interaction. PMID:26441660

Repeated potentiation of the metabotropic glutamate receptor 5 and the alpha 7 nicotinic acetylcholine receptor modulates behavioural and GABAergic deficits induced by early postnatal phencyclidine (PCP) treatment

DEFF Research Database (Denmark)

Kjaerby, Celia; Bundgaard, Christoffer; Fejgin, Kim

2013-01-01

GluR5), ADX47273, and the partial agonist of the α7 nicotinic acetylcholine receptor (α7 nAChR), SSR180711. Adolescent rats (4-5 weeks) subjected to PCP treatment during the second postnatal week displayed a consistent deficit in prepulse inhibition (PPI), which was reversed by a one-week treatment...

Testing a decades' old assumption

DEFF Research Database (Denmark)

Bak, N; Mann, J; Fagerlund, B

2017-01-01

and attention. Parameters from the PPI and P50 suppression paradigms were significantly associated with the distractor effects on strategy formation, cognitive inhibition and flexibility, visual short-term memory, and the level of subjective distraction. Subjectively reported distraction was significantly...... to the effect of distraction on strategy formation, cognitive inhibition and flexibility, as well as visual short term memory. Future studies should investigate if gating deficits affect the distractibility of the same specific cognitive functions in patients with schizophrenia....... with the P50 suppression and pre-pulse inhibition of the startle reflex (PPI) paradigms. Additionally, a neurocognitive test battery was administered in a cross-over design: with/without auditory distraction. Significant effects of distraction were found in response inhibition, and verbal working memory...

A Gap in Time: Extending our Knowledge of Temporal Processing Deficits in the HIV-1 Transgenic Rat.

Science.gov (United States)

McLaurin, Kristen A; Moran, Landhing M; Li, Hailong; Booze, Rosemarie M; Mactutus, Charles F

2017-03-01

Approximately 50 % of HIV-1 seropositive individuals develop HIV-1 associated neurocognitive disorders (HAND), which commonly include alterations in executive functions, such as inhibition, set shifting, and complex problem solving. Executive function deficits in HIV-1 are fairly well characterized, however, relatively few studies have explored the elemental dimensions of neurocognitive impairment in HIV-1. Deficits in temporal processing, caused by HIV-1, may underlie the symptoms of impairment in higher level cognitive processes. Translational measures of temporal processing, including cross-modal prepulse inhibition (PPI), gap-prepulse inhibition (gap-PPI), and gap threshold detection, were studied in mature (ovariectomized) female HIV-1 transgenic (Tg) rats, which express 7 of the 9 HIV-1 genes constitutively throughout development. Cross-modal PPI revealed a relative insensitivity to the manipulation of interstimulus interval (ISI) in HIV-1 Tg animals in comparison to control animals, extending previously reported temporal processing deficits in HIV-1 Tg rats to a more advanced age, suggesting the permanence of temporal processing deficits. In gap-PPI, HIV-1 Tg animals exhibited a relative insensitivity to the manipulation of ISI in comparison to control animals. In gap-threshold detection, HIV-1 Tg animals displayed a profound differential sensitivity to the manipulation of gap duration. Presence of the HIV-1 transgene was diagnosed with 91.1 % accuracy using gap threshold detection measures. Understanding the generality and permanence of temporal processing deficits in the HIV-1 Tg rat is vital to modeling neurocognitive deficits observed in HAND and provides a key target for the development of a diagnostic screening tool.

Superhigh-resolution 200ppi series TFT-LCDs; Chokoseisai 200ppi ekisho display series

Energy Technology Data Exchange (ETDEWEB)

Kawamata, K.; Hirai, H. [Toshiba Corp., Tokyo (Japan)

2000-02-01

We have developed a 202 pixels per inch (ppi) thin-film transistor liquid crystal display (TFT-LCD) using low-temperature polycrystalline silicon (LTPS) technology. The superhigh resolution of 202 ppi offers the same image quality as printed matter such as magazines. The 200 ppi series TFT-LCDs are expected to support further developments in such areas as electronic books (e-books) and personal digital-picture viewers. Our lineup of 200 ppi TFT-LCDs includes a 4-inch display with VGA resolution, which is suitable for palmtop-size applications, and a 6.3-inch display with XGA resolution, which is suitable for typical photograph or paperback book-size applications. Larger size LCDs with 200 ppi resolution will be developed. (author)

Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers

Science.gov (United States)

Quednow, Boris B; Kometer, Michael; Geyer, Mark A; Vollenweider, Franz X

2012-01-01

The serotonin-2A receptor (5-HT2AR) has been implicated in the pathogenesis of schizophrenia and related inhibitory gating and behavioral inhibition deficits of schizophrenia patients. The hallucinogen psilocybin disrupts automatic forms of sensorimotor gating and response inhibition in humans, but it is unclear so far whether the 5-HT2AR or 5-HT1AR agonist properties of its bioactive metabolite psilocin account for these effects. Thus, we investigated whether psilocybin-induced deficits in automatic and controlled inhibition in healthy humans could be attenuated by the 5-HT2A/2CR antagonist ketanserin. A total of 16 healthy participants received placebo, ketanserin (40 mg p.o.), psilocybin (260 μg/kg p.o.), or psilocybin plus ketanserin in a double-blind, randomized, and counterbalanced order. Sensorimotor gating was measured by prepulse inhibition (PPI) of the acoustic startle response. The effects on psychopathological core dimensions and behavioral inhibition were assessed by the altered states of consciousness questionnaire (5D-ASC), and the Color-Word Stroop Test. Psilocybin decreased PPI at short lead intervals (30 ms), increased all 5D-ASC scores, and selectively increased errors in the interference condition of the Stroop Test. Stroop interference and Stroop effect of the response latencies were increased under psilocybin as well. Psilocybin-induced alterations were attenuated by ketanserin pretreatment, whereas ketanserin alone had no significant effects. These findings suggest that the disrupting effects of psilocybin on automatic and controlled inhibition processes are attributable to 5-HT2AR stimulation. Sensorimotor gating and attentional control deficits of schizophrenia patients might be due to changes within the 5-HT2AR system. PMID:21956447

The effects of increased central serotonergic activity on prepulse inhibition and habituation of the human startle response

DEFF Research Database (Denmark)

Jensen, Kristian S; Oranje, Bob; Wienberg, Malene

2007-01-01

modulation is currently inconsistent. In a double-blind placebo-controlled crossover design, 18 healthy male volunteers received either placebo or a dose of 10 mg of escitalopram (SSRI), after which they were tested in both PPI and habituation of the startle reflex paradigms. No significant differences...... between the two treatments were observed on PPI, although escitalopram was found to significantly delay habituation of the ASR. In the current study, escitalopram was found to delay habituation, but it did not affect PPI in healthy male volunteers. As escitalopram is a highly specific SSRI, the results...

Controlling output pulse and prepulse in a resonant microwave pulse compressor

International Nuclear Information System (INIS)

Shlapakovski, A.; Artemenko, S.; Chumerin, P.; Yushkov, Yu.

2013-01-01

A resonant microwave pulse compressor with a waveguide H-plane-tee-based energy extraction unit was studied in terms of its capability to produce output pulses that comprise a low-power long-duration (prepulse) and a high-power short-duration part. The application of such combined pulses with widely variable prepulse and high-power pulse power and energy ratios is of interest in the research area of electronic hardware vulnerability. The characteristics of output radiation pulses are controlled by the variation of the H-plane tee transition attenuation at the stage of microwave energy storage in the compressor cavity. Results of theoretical estimations of the parameters tuning range and experimental investigations of the prototype S-band compressor (1.5 MW, 12 ns output pulse; ∼13.2 dB gain) are presented. The achievable maximum in the prepulse power is found to be about half the power of the primary microwave source. It has been shown that the energy of the prepulse becomes comparable with that of the short-duration (nanosecond) pulse, while the power of the latter decreases insignificantly. The possible range of variation of the prepulse power and energy can be as wide as 40 dB. In the experiments, the prepulse level control within the range of ∼10 dB was demonstrated.

An analysis of inhibitory functioning in individuals with chronic posttraumatic stress disorder.

Science.gov (United States)

Echiverri-Cohen, Aileen M; Zoellner, Lori A; Ho, William; Husain, Jawad

2016-01-01

Cognitive abnormalities in posttraumatic stress disorder (PTSD) may be a function of underlying inhibitory deficits. Prepulse inhibition (PPI) and attentional blink (AB) are paradigms thought to assess inhibition. Using a sample of 28 individuals with PTSD compared to 20 trauma-exposed and 19 healthy individuals, PPI was examined using white noise that was preceded by a tone, and AB was examined using a presentation of letters in a stream of numbers. Relative to the control group, the PTSD and trauma-exposed groups did not follow the u-shaped pattern in AB, suggesting trauma-exposure and subsequent PTSD are associated with similar impairment in attention. Individuals with PTSD showed reduced PPI compared to trauma-exposed and healthy individuals, suggesting individuals with PTSD exhibit faulty automatic processing. For individuals with PTSD, PTSD severity was associated with a decline in PPI. These findings suggest a general faulty inhibitory mechanism associated with trauma exposure and PTSD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Surfing the Protein-Protein Interaction Surface Using Docking Methods: Application to the Design of PPI Inhibitors.

Science.gov (United States)

Sable, Rushikesh; Jois, Seetharama

2015-06-23

Blocking protein-protein interactions (PPI) using small molecules or peptides modulates biochemical pathways and has therapeutic significance. PPI inhibition for designing drug-like molecules is a new area that has been explored extensively during the last decade. Considering the number of available PPI inhibitor databases and the limited number of 3D structures available for proteins, docking and scoring methods play a major role in designing PPI inhibitors as well as stabilizers. Docking methods are used in the design of PPI inhibitors at several stages of finding a lead compound, including modeling the protein complex, screening for hot spots on the protein-protein interaction interface and screening small molecules or peptides that bind to the PPI interface. There are three major challenges to the use of docking on the relatively flat surfaces of PPI. In this review we will provide some examples of the use of docking in PPI inhibitor design as well as its limitations. The combination of experimental and docking methods with improved scoring function has thus far resulted in few success stories of PPI inhibitors for therapeutic purposes. Docking algorithms used for PPI are in the early stages, however, and as more data are available docking will become a highly promising area in the design of PPI inhibitors or stabilizers.

Psilocybin-induced deficits in automatic and controlled inhibition are attenuated by ketanserin in healthy human volunteers.

Science.gov (United States)

Quednow, Boris B; Kometer, Michael; Geyer, Mark A; Vollenweider, Franz X

2012-02-01

The serotonin-2A receptor (5-HT(2A)R) has been implicated in the pathogenesis of schizophrenia and related inhibitory gating and behavioral inhibition deficits of schizophrenia patients. The hallucinogen psilocybin disrupts automatic forms of sensorimotor gating and response inhibition in humans, but it is unclear so far whether the 5-HT(2A)R or 5-HT(1A)R agonist properties of its bioactive metabolite psilocin account for these effects. Thus, we investigated whether psilocybin-induced deficits in automatic and controlled inhibition in healthy humans could be attenuated by the 5-HT(2A/2C)R antagonist ketanserin. A total of 16 healthy participants received placebo, ketanserin (40 mg p.o.), psilocybin (260 μg/kg p.o.), or psilocybin plus ketanserin in a double-blind, randomized, and counterbalanced order. Sensorimotor gating was measured by prepulse inhibition (PPI) of the acoustic startle response. The effects on psychopathological core dimensions and behavioral inhibition were assessed by the altered states of consciousness questionnaire (5D-ASC), and the Color-Word Stroop Test. Psilocybin decreased PPI at short lead intervals (30 ms), increased all 5D-ASC scores, and selectively increased errors in the interference condition of the Stroop Test. Stroop interference and Stroop effect of the response latencies were increased under psilocybin as well. Psilocybin-induced alterations were attenuated by ketanserin pretreatment, whereas ketanserin alone had no significant effects. These findings suggest that the disrupting effects of psilocybin on automatic and controlled inhibition processes are attributable to 5-HT(2A)R stimulation. Sensorimotor gating and attentional control deficits of schizophrenia patients might be due to changes within the 5-HT(2A)R system.

Surfing the Protein-Protein Interaction Surface Using Docking Methods: Application to the Design of PPI Inhibitors

Directory of Open Access Journals (Sweden)

Rushikesh Sable

2015-06-01

Full Text Available Blocking protein-protein interactions (PPI using small molecules or peptides modulates biochemical pathways and has therapeutic significance. PPI inhibition for designing drug-like molecules is a new area that has been explored extensively during the last decade. Considering the number of available PPI inhibitor databases and the limited number of 3D structures available for proteins, docking and scoring methods play a major role in designing PPI inhibitors as well as stabilizers. Docking methods are used in the design of PPI inhibitors at several stages of finding a lead compound, including modeling the protein complex, screening for hot spots on the protein-protein interaction interface and screening small molecules or peptides that bind to the PPI interface. There are three major challenges to the use of docking on the relatively flat surfaces of PPI. In this review we will provide some examples of the use of docking in PPI inhibitor design as well as its limitations. The combination of experimental and docking methods with improved scoring function has thus far resulted in few success stories of PPI inhibitors for therapeutic purposes. Docking algorithms used for PPI are in the early stages, however, and as more data are available docking will become a highly promising area in the design of PPI inhibitors or stabilizers.

Using prepulsing: a useful way for increasing absorption efficiency of high intensity laser beam

International Nuclear Information System (INIS)

Peng Huimin; Zhang Guoping; Sheng Jiatian

1990-01-01

Using prepulse to irradiate target for increasing absorption efficiency of high intensity incident laser beam is considered and some theoretical simulations have been done. 1-D non-LTE radiative hydrodynamic code is used to simulate the interactions of laser beam with matter. A gaussian laser prepulse of wavelength 1.06 μm, FWHM 600 ps and peak intensity 1.5 x 10 12 W/cm 2 was used to irradiate 20 μm thick Au plate target, after 3ns a main gaussian pulse with wavelength 1.06 μm, FWHM 600 ps and peak intensity 3.0 x 10 14 W/cm 2 irradiated the expanding Au plasma. The responces of laser-produced plasma conditions are shown. By comparing with without prepulsing, under the condition of same main incident laser pulse, the absorption efficiency is increased from 0.36 to 0.60 and the laser-x-ray conversion efficiency is increased from 0.16 to 0.25. The electron temperature of hot plasma is also higher than without prepulsing, and the x-ray spectrum which is emitted from laser-produced hot plasma is harder and more intense than without prepulsing. The responces of laser-produced plasma for Fe target with prepulsing are shown as well. The conclusion is that using prepulsing is a useful way for getting high absorption laser beam

Low prepulse, high power density water dielectric switching

International Nuclear Information System (INIS)

Johnson, D.L.; VanDevender, J.P.; Martin, T.H.

1979-01-01

Prepulse voltage suppression has proven difficult in high power, high voltage accelerators employing self-breakdown water dielectric switches. A novel and cost effective water switch has been developed at Sandia Laboratories which reduces prepulse voltage by reducing the capacity across the switch. This prepulse suppression switch causes energy formerly stored in the switch capacity and dissipated in the arc to be useful output energy. The switching technique also allows the pulse forming lines to be stacked in parallel and electrically isolated from the load after the line has been discharged. The switch consists of a ground plane, with several holes, inserted between the switch electrodes. The output line switch electrodes extend through the holes and face electrodes on the pulse forming line (PFL). The capacity between the PFL and the output transmission line is reduced by about 80%. The gap spacing between the output line electrode and the hole in the ground plane is adjusted so that breakdown occurs after the main pulse and provides a crow bar between the load and the source. Performance data from the Proto II, Mite and Ripple test facilities are presented

PPI, paradoxes and Plato: who's sailing the ship?

Science.gov (United States)

Ives, Jonathan; Damery, Sarah; Redwod, Sabi

2013-03-01

Over the last decade, patient and public involvement (PPI) has become a requisite in applied health research. Some funding bodies demand explicit evidence of PPI, while others have made a commitment to developing PPI in the projects they fund. Despite being commonplace, there remains a dearth of engagement with the ethical and theoretical underpinnings of PPI processes and practices. More specifically, while there is a small (but growing) body of literature examining the effectiveness and impact of PPI, there has been relatively little reflection on whether the concept/practice of PPI is internally coherent. Here, the authors unpick a 'paradox' within PPI, which highlights a tension between its moral and pragmatic motivations and its implementation. The authors argue that this 'professionalisation paradox' means we need to rethink the practice, and purpose, of PPI in research.

The effects of prepulse-blink reflex trial repetition and prepulse change on blink reflex modification at short and long lead intervals.

Science.gov (United States)

Lipp, O V; Siddle, D A

1998-01-01

Prepulse inhibition and facilitation of the blink reflex are said to reflect different responses elicited by the lead stimulus, transient detection and orienting response respectively. Two experiments investigated the effects of trial repetition and lead stimulus change on blink modification. It was hypothesized that these manipulations will affect orienting and thus blink facilitation to a greater extent than they will affect transient detection and thus blink inhibition. In Experiment 1 (N = 64), subjects were trained with a sequence of 12 lead stimulus and 12 blink stimulus alone presentations, and 24 lead stimulus-blink stimulus pairings. Lead interval was 120 ms for 12 of the trials and 2000 ms for the other 12. For half the subjects this sequence was followed by a change in pitch of the lead stimulus. In Experiment 2 (N = 64), subjects were trained with a sequence of 36 blink alone stimuli and 36 lead stimulus-blink stimulus pairings. The lead interval was 120 ms for half the subjects and 2000 ms for the other half. The pitch of the lead stimulus on prestimulus trials 31-33 was changed for half the subjects in each group. In both experiments, the amount of blink inhibition decreased during training whereas the amount of blink facilitation remained unchanged. Lead stimulus change had no effect on blink modification in either experiment although it resulted in enhanced skin conductance responses and greater heart rate deceleration in Experiment 2. The present results are not consistent with the notion that blink facilitation is linked to orienting whereas blink inhibition reflects a transient detection mechanism.

The effects of insulating coatings and current prepulse on tungsten planar wire array Z-pinches

Energy Technology Data Exchange (ETDEWEB)

Li, M., E-mail: limo@nint.ac.cn; Li, Y. [State Key Laboratory of Electrical Insulation and Power Equipment, Xi' an Jiaotong University, Shaanxi 710049 (China); State Key Laboratory of Intense Pulsed Radiation Simulation and Effect, Northwest Institute of Nuclear Technology, Xi' an 710024 (China); Sheng, L.; Wang, L. P.; Zhao, C.; Yuan, Y.; Zhang, X. J.; Zhang, M.; Peng, B. D.; Zhang, J. H.; Zhang, S. G.; Qiu, M. T. [State Key Laboratory of Intense Pulsed Radiation Simulation and Effect, Northwest Institute of Nuclear Technology, Xi' an 710024 (China); Li, X. W. [State Key Laboratory of Electrical Insulation and Power Equipment, Xi' an Jiaotong University, Shaanxi 710049 (China)

2015-12-15

This paper presents experimental results on the effects of insulating coatings and current prepulse on tungsten planar wire array Z-pinches on ∼100 ns main current facility. Optical framing images indicated that without a current prepulse the wire ablation process was asymmetrical and the implosion was zippered. The x-ray peak power was ∼320 GW. By using insulating coatings on the wire surface the asymmetry remained, and the processes of ablation and implosion were delayed by ∼30 ns. The x-ray burst was narrow and decreased to ∼200 GW. When current prepulses were used on both standard and insulated wire arrays, implosion symmetry was improved and the x-ray burst was improved (to ∼520 GW peak power). In addition, there was a strong emitting precursor column for insulated loads with the current prepulse.

Sensorimotor gating characteristics of violent men with comorbid psychosis and dissocial personality disorder: Relationship with antisocial traits and psychosocial deprivation.

Science.gov (United States)

Sedgwick, Ottilie; Young, Susan; Greer, Ben; Arnold, Jack; Parsons, Aisling; Puzzo, Ignazio; Terracciano, Mariafatima; Das, Mrigendra; Kumari, Veena

2017-07-06

Evidence suggests violence amongst those with psychosis is not aetiologically homogeneous, and that a large proportion of those who engage in violent behaviour have a comorbid antisocial personality disorder. Initial investigations indicate that this subgroup has distinct historical and neuropsychological characteristics, which may indicate diverse treatment needs. This study investigated sensorimotor gating characteristics of violent men with diagnoses of both psychosis and dissocial personality disorder (DPD) (n=21) relative to violent men with psychosis alone (n=12), DPD alone (n=14) and healthy, non-violent male controls (n=27), using the prepulse inhibition (PPI) paradigm. The results indicated that, relative to the psychosis alone and healthy control groups, the comorbid group had lower PPI, especially at 60-ms prepulse-to-pulse interval. The DPD group took an intermediary position and did not differ from any group. Antisocial personality traits (factor two scores of the Psychopathy Checklist - Revised), and greater severity of childhood psychosocial deprivation (including physical and sexual abuse), were significantly correlated with poor PPI across the clinical sample. The findings suggest diverse sensorimotor gating profiles amongst subgroups of violent offenders, with comorbid psychosis and DPD showing most impairment. This is consistent with a 'double dose' of deficit explanation amongst those with both diagnoses, explained at least in part by presence of antisocial personality traits and childhood psychosocial deprivation. Copyright © 2017 Elsevier B.V. All rights reserved.

Plasma formation and target preheating by prepulse of PW laser light

Science.gov (United States)

Sentoku, Yasuhiko; Iwata, Natsumi; Koga, James; Dover, Nicholas; Nishiuchi, Mamiko

2017-10-01

An intense short pulse laser with intensity over 1021 W/cm2 has become available, i.e. J-KAREN-P at QST. Although the contrast of the short pulse is improved to be of the order of 10-11, there is an unavoidable prepulse, which has multiple spikes (ps) on top of an exponential profile with intensity greater than 1014 W/cm2 about 50 ps in front of the main pulse. The prepulse preheats the target and also produces tenuous plasmas in front of a target before the main pulse arrives. It is critical to understand such preheating of the target, where the nonlocal heat transport is essential at intensity >1014 W/cm2, since the target condition might totally change before the interaction with the main pulse. Using a hydro code, FLASH, and a collisional particle-in-cell code, PICLS, we study the preplasma formation and target preheating over tens of picoseconds timescale, and discuss the prepulse effects on the main pulse interaction. Work supported by the JSPS KAKENHI under Grant No. JP15K21767.

32 CFR 701.115 - Protected personal information (PPI).

Science.gov (United States)

2010-07-01

... Section 701.115 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY UNITED STATES... information (PPI). (a) Access/disclosure. Access to and disclosure of PPI such as SSN, date of birth, home... notice and understand PA rules. DON activities shall ensure that PPI (e.g., home address, date of birth...

Tolerance of laser-driven microshell targets to fluorescence and prepulse energy

International Nuclear Information System (INIS)

Leonard, T.; Moncur, N.K.; Sullivan, D.

1976-01-01

Glass-shell targets currently being used for laser-fusion experiments are susceptible to damage by preenergy from the laser. This energy can result from amplified spontaneous emission (ASE) throughout the laser chain during the period of high-population inversion or it can take the form of a short prepulse nanoseconds before the main laser pulse. We point out the energy levels which a typical target can tolerate in the form of ASE and prepulses. These energies are low enough that special precautions must be taken to prevent significant perturbations of the target or its environment before the main laser pulse

Psychophysiological deficits in young adolescents with psychosis or ADHD: Preliminary findings

DEFF Research Database (Denmark)

Rydkjær, Jacob; Jepsen, Jens Richardt Møllegaard; Fagerlund, Birgitte

add valuable information on how to differentiate premature stages of early onset psychosis from ADHD. Aim: To characterize psychophysiological deficits in young adolescents with psychosis or ADHD and compare the profiles of impariments between the two groups. Materials and methods: A cohort of young...... and low intensity prepulse trials, Mismatch Negativity (MMN), Selective Attention (SA) and P50. Results: Preliminary analyses of 18 patients with psychosis and 12 patients with ADHD showed significantly less PPI in the higher intensity prepulse trials in the psychosis group than in the ADHD group....... No significant group difference was found in the lower intensity prepulse trials. Conclusion: The preliminary results indicate lower levels of PPI in adolescents with early onset psychosis than in young patients with ADHD. If these results hold in the final analyses then this knowledge may contribute to better...

Sensory Gating Deficits in First-Episode Psychosis: Evidence From Neurophysiology, Psychophysiology, and Neuropsychology.

Science.gov (United States)

Morales-Muñoz, Isabel; Jurado-Barba, Rosa; Fernández-Guinea, Sara; Rodríguez-Jiménez, Roberto; Jiménez-Arriero, Miguel Ángel; Criado, José R; Rubio, Gabriel

2016-12-01

Sensory gating deficits are commonly found in patients with schizophrenia. However, there is still scarce research on this issue. Thirty-eight patients with first-episode psychosis (FEP) were compared to thirty-eight controls. A condition-test paradigm of event-related potentials (ERP), prepulse inhibition (PPI), and some specific tasks of the MATRICS Consensus Cognitive Battery (MCCB) were used (i.e., TMT, BACS-SC, and Fluency for processing speed and CPT-IP for attention and vigilance). The ERP components measured were P50, N1, and P2. The PPI intervals examined were 30, 60, and 120 msec. Regarding the MCCB, processing speed and attention/vigilance cognitive domains were selected. FEP patients showed significant deficits in N1 and P2 components, at 30 and 60 PPI levels and in all the MCCB subtests selected. We obtained significant relationships in N1 with PPI-60, and with one MCCB subtest for processing speed. In addition, this same subtest showed significant association with P2. Therefore, sensory gating functioning is widely impaired since the very early stages of schizophrenia.

Preparation and characterization of visible light-driven AgCl/PPy photocatalyst

International Nuclear Information System (INIS)

Gu Shuna; Li Bing; Zhao Chongjun; Xu Yunlong; Qian Xiuzhen; Chen, Guorong

2011-01-01

Graphical abstract: AgCl/PPy composite exhibits improved photocatalytic performance and high stability under visible light. Display Omitted Highlights: → AgCl/(PPy) nanocomposites as visible light driven photocatalyst. → Composites exhibited high visible light-driven photocatalytic activity and stability. → Photocatalytic process on MO followed photoreduction mechanisms. → Used photocatalyst can be regenerated in aqueous FeCl 3 solution. - Abstract: Visible light photoactive AgCl/polypyrrole (PPy) composites were prepared via the reaction between excessive Ag + and Cl - ions in the presence of PPy . The AgCl/PPy composites were systematically characterized using Fourier transform infrared (FTIR) spectroscopy, Raman spectra, X-ray diffraction (XRD), Scanning electron microscope (SEM), Transmission electron microscope (TEM) and Thermal gravity analysis (TGA). It was found that face-centered cubic AgCl nanocrystallite and 0.2 wt% PPy component existed in the composite and spherical AgCl/PPy nanoparticles were in the range of 200-600 nm. The AgCl/PPy composites showed higher visible light-driven photocatalytic activity and stability than that of AgCl. A photoreduction mechanism was postulated for AgCl/PPy photocatalyst on dye methyl orange (MO). The used AgCl/PPy photocatalyst was facilely regenerated by an oxidation process in aqueous FeCl 3 solution.

Preparation and characterization of visible light-driven AgCl/PPy photocatalyst

Energy Technology Data Exchange (ETDEWEB)

Gu Shuna; Li Bing [Key Laboratory for Ultrafine Materials of Ministry of Education, Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Zhao Chongjun, E-mail: chongjunzhao@ecust.edu.cn [Key Laboratory for Ultrafine Materials of Ministry of Education, Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Xu Yunlong; Qian Xiuzhen; Chen, Guorong [Key Laboratory for Ultrafine Materials of Ministry of Education, Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China)

2011-05-05

Graphical abstract: AgCl/PPy composite exhibits improved photocatalytic performance and high stability under visible light. Display Omitted Highlights: > AgCl/(PPy) nanocomposites as visible light driven photocatalyst. > Composites exhibited high visible light-driven photocatalytic activity and stability. > Photocatalytic process on MO followed photoreduction mechanisms. > Used photocatalyst can be regenerated in aqueous FeCl{sub 3} solution. - Abstract: Visible light photoactive AgCl/polypyrrole (PPy) composites were prepared via the reaction between excessive Ag{sup +} and Cl{sup -} ions in the presence of PPy{sub .} The AgCl/PPy composites were systematically characterized using Fourier transform infrared (FTIR) spectroscopy, Raman spectra, X-ray diffraction (XRD), Scanning electron microscope (SEM), Transmission electron microscope (TEM) and Thermal gravity analysis (TGA). It was found that face-centered cubic AgCl nanocrystallite and 0.2 wt% PPy component existed in the composite and spherical AgCl/PPy nanoparticles were in the range of 200-600 nm. The AgCl/PPy composites showed higher visible light-driven photocatalytic activity and stability than that of AgCl. A photoreduction mechanism was postulated for AgCl/PPy photocatalyst on dye methyl orange (MO). The used AgCl/PPy photocatalyst was facilely regenerated by an oxidation process in aqueous FeCl{sub 3} solution.

Use of pre-pulse in laser spot welding of materials with high optical reflection

Science.gov (United States)

Mys, Ihor; Geiger, Manfred

2003-11-01

Laser micro welding has become a standard manufacturing technique, particularly in industry sectors, such as automotive and aerospace electronics or medical devices, where the requirements for strength, miniaturization and temperature resistance are constantly rising. So far the use of laser micro welding is limited due to the fluctuation of the quality of the welded joints, because the welding results for material with high optical reflection and thermal conductivity, such as copper and copper alloys, depend very strongly on the condition of the material surface. This paper presents investigations on the use of a laser pre-pulse in spot welding of electronic materials with Nd:YAG laser. In order to achieve reproducible joining results two strategies are followed-up. The first one utilizes a reflection-based process control for measuring the reflection during the short pre-pulse. The intensity of the reflected light is used to calculate an appropriated welding pulse power, which corresponds to the measured relative absorption. Adjustment of laser parameters according to the condition of the surface is done in real time before laser main pulse. A second possibility for the stabilization of copper welding is the employment of a short and powerful laser pre-pulse before laser main pulse. This pre-pulse affects the workpiece surface and creates more reproducible absorption conditions for the main pulse, independent from the initial situation on material surface.

RADAR PPI Scope Overlay

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — RADAR PPI Scope Overlays are used to position a RADAR image over a station at the correct resolution. The archive maintains several different RADAR resolution types,...

Fabp7 Maps to a Quantitative Trait Locus for a Schizophrenia Endophenotype

Science.gov (United States)

Watanabe, Akiko; Toyota, Tomoko; Owada, Yuji; Hayashi, Takeshi; Iwayama, Yoshimi; Matsumata, Miho; Ishitsuka, Yuichi; Nakaya, Akihiro; Maekawa, Motoko; Ohnishi, Tetsuo; Arai, Ryoichi; Sakurai, Katsuyasu; Yamada, Kazuo; Kondo, Hisatake; Hashimoto, Kenji; Osumi, Noriko; Yoshikawa, Takeo

2007-01-01

Deficits in prepulse inhibition (PPI) are a biological marker for schizophrenia. To unravel the mechanisms that control PPI, we performed quantitative trait loci (QTL) analysis on 1,010 F2 mice derived by crossing C57BL/6 (B6) animals that show high PPI with C3H/He (C3) animals that show low PPI. We detected six major loci for PPI, six for the acoustic startle response, and four for latency to response peak, some of which were sex-dependent. A promising candidate on the Chromosome 10-QTL was Fabp7 (fatty acid binding protein 7, brain), a gene with functional links to the N-methyl-D-aspartic acid (NMDA) receptor and expression in astrocytes. Fabp7-deficient mice showed decreased PPI and a shortened startle response latency, typical of the QTL's proposed effects. A quantitative complementation test supported Fabp7 as a potential PPI-QTL gene, particularly in male mice. Disruption of Fabp7 attenuated neurogenesis in vivo. Human FABP7 showed altered expression in schizophrenic brains and genetic association with schizophrenia, which were both evident in males when samples were divided by sex. These results suggest that FABP7 plays a novel and crucial role, linking the NMDA, neurodevelopmental, and glial theories of schizophrenia pathology and the PPI endophenotype, with larger or overt effects in males. We also discuss the results from the perspective of fetal programming. PMID:18001149

OCD is associated with an altered association between sensorimotor gating and cortical and subcortical 5-HT1b receptor binding.

Science.gov (United States)

Pittenger, Christopher; Adams, Thomas G; Gallezot, Jean-Dominique; Crowley, Michael J; Nabulsi, Nabeel; James Ropchan; Gao, Hong; Kichuk, Stephen A; Simpson, Ryan; Billingslea, Eileen; Hannestad, Jonas; Bloch, Michael; Mayes, Linda; Bhagwagar, Zubin; Carson, Richard E

2016-05-15

Obsessive-compulsive disorder (OCD) is characterized by impaired sensorimotor gating, as measured using prepulse inhibition (PPI). This effect may be related to abnormalities in the serotonin (5-HT) system. 5-HT1B agonists can impair PPI, produce OCD-like behaviors in animals, and exacerbate OCD symptoms in humans. We measured 5-HT1B receptor availability using (11)C-P943 positron emission tomography (PET) in unmedicated, non-depressed OCD patients (n=12) and matched healthy controls (HC; n=12). Usable PPI data were obtained from 20 of these subjects (10 from each group). There were no significant main effects of OCD diagnosis on 5-HT1B receptor availability ((11)C-P943 BPND); however, the relationship between PPI and (11)C-P943 BPND differed dramatically and significantly between groups. 5-HT1B receptor availability in the basal ganglia and thalamus correlated positively with PPI in controls; these correlations were lost or even reversed in the OCD group. In cortical regions there were no significant correlations with PPI in controls, but widespread positive correlations in OCD patients. Positive correlations between 5-HT1B receptor availability and PPI were consistent across diagnostic groups only in two structures, the orbitofrontal cortex and the amygdala. Differential associations of 5-HT1B receptor availability with PPI in patients suggest functionally important alterations in the serotonergic regulation of cortical/subcortical balance in OCD. Copyright © 2016 Elsevier B.V. All rights reserved.

Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype.

Directory of Open Access Journals (Sweden)

Akiko Watanabe

2007-11-01

Full Text Available Deficits in prepulse inhibition (PPI are a biological marker for schizophrenia. To unravel the mechanisms that control PPI, we performed quantitative trait loci (QTL analysis on 1,010 F2 mice derived by crossing C57BL/6 (B6 animals that show high PPI with C3H/He (C3 animals that show low PPI. We detected six major loci for PPI, six for the acoustic startle response, and four for latency to response peak, some of which were sex-dependent. A promising candidate on the Chromosome 10-QTL was Fabp7 (fatty acid binding protein 7, brain, a gene with functional links to the N-methyl-D-aspartic acid (NMDA receptor and expression in astrocytes. Fabp7-deficient mice showed decreased PPI and a shortened startle response latency, typical of the QTL's proposed effects. A quantitative complementation test supported Fabp7 as a potential PPI-QTL gene, particularly in male mice. Disruption of Fabp7 attenuated neurogenesis in vivo. Human FABP7 showed altered expression in schizophrenic brains and genetic association with schizophrenia, which were both evident in males when samples were divided by sex. These results suggest that FABP7 plays a novel and crucial role, linking the NMDA, neurodevelopmental, and glial theories of schizophrenia pathology and the PPI endophenotype, with larger or overt effects in males. We also discuss the results from the perspective of fetal programming.

Synthesis and microwave absorption properties of PPy/Co nanocomposites

Energy Technology Data Exchange (ETDEWEB)

Luo, Juhua, E-mail: luojuhua@163.com [School of Materials Engineering, Yancheng Institute of Technology, Yancheng 224051 (China); Gao, Duoduo [School of Material Science and Engineering, Changzhou University, Changzhou 213164 (China)

2014-11-15

Polypyrrole (PPy)/cobalt (Co) nanocomposites were successfully prepared by an in-situ polymerization of pyrrole in the presence of synthesized Co nanoparticles. Characterization of the product was accomplished by XRD, TEM, FT-IR, VSM, and vector network analyzer techniques. XRD analysis revealed that characteristic diffraction peaks of polypyrrole and Co appeared at the same time in nanocomposites. FT-IR analysis indicated a successful conjugation of Co particles with polypyrrole. TEM confirmed the formation of a core-shell structure with a wide particle size distribution. Magnetization measurements showed that polypyrrole coating decreased the saturation magnetization of Co significantly. With the increase of the matching thickness, the absorption peak varied towards low frequency direction. When the matching thickness was 3.0 mm, the value of the maximum reflection loss (RL) was −20.0 dB at 13.8 GHz with the 7.2 GHz bandwidth. - Highlights: • The influence of PPy on the structure of Co is discussed. • The influence of PPy on the magnetic properties of Co is discussed. • The influence of PPy on the absorption property of Co is discussed. • PPy/Co possessed the excellent absorption property.

Chemically designed Pt/PPy nano-composite for effective LPG gas sensor.

Science.gov (United States)

Gaikwad, Namrata; Bhanoth, Sreenu; More, Priyesh V; Jain, G H; Khanna, P K

2014-03-07

Simultaneous in situ reduction of hexachloroplatinic acid by the amine group in the pyrrole monomer and oxidation of pyrrole to form polypyrrole (PPy) was examined. The reactions were performed at various temperatures to understand the degree of reduction of platinum precursor as well as doping of polypyrrole with Pt(II) chloro-complex. Spectroscopic images revealed different morphologies for the Pt/PPy nano-composite prepared at various temperatures. The as-prepared Pt/PPy nano-composite samples were tested for their ability to sense liquefied petroleum gas (LPG) which resulted in excellent sensing at relatively low temperature. The porous nature and ohmic contact between the PPy and platinum nanoparticles makes the as-prepared Pt/PPy nano-composite highly useful for sensors as well as electronic applications.

Pregnenolone rescues schizophrenia-like behavior in dopamine transporter knockout mice.

Directory of Open Access Journals (Sweden)

Peiyan Wong

Full Text Available Pregnenolone belongs to a class of endogenous neurosteroids in the central nervous system (CNS, which has been suggested to enhance cognitive functions through GABA(A receptor signaling by its metabolites. It has been shown that the level of pregnenolone is altered in certain brain areas of schizophrenic patients, and clozapine enhances pregnenolone in the CNS in rats, suggesting that pregnenolone could be used to treat certain symptoms of schizophrenia. In addition, early phase proof-of-concept clinical trials have indicated that pregnenolone is effective in reducing the negative symptoms and cognitive deficits of schizophrenia patients. Here, we evaluate the actions of pregnenolone on a mouse model for schizophrenia, the dopamine transporter knockout mouse (DAT KO. DAT KO mice mirror certain symptoms evident in patients with schizophrenia, such as the psychomotor agitation, stereotypy, deficits of prepulse inhibition and cognitive impairments. Following acute treatment, pregnenolone was found to reduce the hyperlocomotion, stereotypic bouts and pre-pulse inhibition (PPI deficits in DAT KO mice in a dose-dependent manner. At 60 mg/kg of pregnenolone, there were no significant differences in locomotor activities and stereotypy between wild-type and DAT KO mice. Similarly, acute treatment of 60 mg/kg of pregnenolone fully rescued PPI deficits of DAT KO mice. Following chronic treatment with pregnenolone at 60 mg/kg, the cognitive deficits of DAT KO mice were rescued in the paradigms of novel object recognition test and social transmission of food preference test. Pregnenolone thus holds promise as a therapeutic candidate in schizophrenia.

Sensitivity of PPI analysis to differences in noise reduction strategies.

Science.gov (United States)

Barton, M; Marecek, R; Rektor, I; Filip, P; Janousova, E; Mikl, M

2015-09-30

In some fields of fMRI data analysis, using correct methods for dealing with noise is crucial for achieving meaningful results. This paper provides a quantitative assessment of the effects of different preprocessing and noise filtering strategies on psychophysiological interactions (PPI) methods for analyzing fMRI data where noise management has not yet been established. Both real and simulated fMRI data were used to assess these effects. Four regions of interest (ROIs) were chosen for the PPI analysis on the basis of their engagement during two tasks. PPI analysis was performed for 32 different preprocessing and analysis settings, which included data filtering with RETROICOR or no such filtering; different filtering of the ROI "seed" signal with a nuisance data-driven time series; and the involvement of these data-driven time series in the subsequent PPI GLM analysis. The extent of the statistically significant results was quantified at the group level using simple descriptive statistics. Simulated data were generated to assess statistical improvement of different filtering strategies. We observed that different approaches for dealing with noise in PPI analysis yield differing results in real data. In simulated data, we found RETROICOR, seed signal filtering and the addition of data-driven covariates to the PPI design matrix significantly improves results. We recommend the use of RETROICOR, and data-driven filtering of the whole data, or alternatively, seed signal filtering with data-driven signals and the addition of data-driven covariates to the PPI design matrix. Copyright © 2015 Elsevier B.V. All rights reserved.

[Study on the land use optimization based on PPI].

Science.gov (United States)

Wu, Xiao-Feng; Li, Ting

2012-03-01

Land use type and managing method which is greatly influenced by human activities, is one of the most important factors of non-point pollution. Based on the collection and analysis of non-point pollution control methods and the concept of the three ecological fronts, 9 land use optimized scenarios were designed according to rationality analysis of the current land use situation in the 3 typed small watersheds in Miyun reservoir basin. Take Caojialu watershed for example to analyze and compare the influence to environment of different scenarios based on potential pollution index (PPI) and river section potential pollution index (R-PPI) and the best combination scenario was found. Land use scenario designing and comparison on basis of PPI and R-PPI could help to find the best combination scenario of land use type and managing method, to optimize space distribution and managing methods of land use in basin, to reduce soil erosion and to provide powerful support to formulation of land use planning and pollution control project.

Oxadiazole-carbazole polymer (POC)-Ir(ppy)3 tunable emitting composites

Science.gov (United States)

Bruno, Annalisa; Borriello, Carmela; Di Luccio, Tiziana; Sessa, Lucia; Concilio, Simona; Haque, Saif A.; Minarini, Carla

2017-04-01

POC polymer is an oxadiazole-carbazole copolymer we have previously synthetized and established as light emitting material in Organic Light Emitting Devices (OLEDs), although POC quantum yield emission efficiency and color purity still need to be enhanced. On the other hand, tris[2-phenylpyridinato-C2,N]iridium(III) (Ir(ppy)3) complexes, namely Ir(ppy)3 are among the brightest luminophores employed in green light emitting devices. Our aim, in this work, is to take advantage of Ir(ppy)3 bright emission by combining the Ir complex with blue emitting POC to obtain tunable light emitting composites over a wide range of the visible spectrum. Here we have investigated the optical proprieties POC based nanocomposites with different concentrations of Ir(ppy)3, ranging from 1 to 10 wt%. Both spectral and time resolved fluorescence measurements show an efficient energy transfer from the polymer to the dopants, resulting in white-emitting composites. The most intense and stable emission has been found when POC was doped with about 5 wt% concentration of Ir(ppy)3.

FMFinder: A Functional Module Detector for PPI Networks

Directory of Open Access Journals (Sweden)

M. Modi

2017-10-01

Full Text Available Bioinformatics is an integrated area of data mining, statistics and computational biology. Protein-Protein Interaction (PPI network is the most important biological process in living beings. In this network a protein module interacts with another module and so on, forming a large network of proteins. The same set of proteins which takes part in the organic courses of biological actions is detected through the Function Module Detection method. Clustering process when applied in PPI networks is made of proteins which are part of a larger communication network. As a result of this, we can define the limits for module detection as well as clarify the construction of a PPI network. For understating the bio-mechanism of various living beings, a detailed study of FMFinder detection by clustering process is called for.

Hohlraum glint and laser pre-pulse detector for NIF experiments using velocity interferometer system for any reflector.

Science.gov (United States)

Moody, J D; Clancy, T J; Frieders, G; Celliers, P M; Ralph, J; Turnbull, D P

2014-11-01

Laser pre-pulse and early-time laser reflection from the hohlraum wall onto the capsule (termed "glint") can cause capsule imprint and unwanted early-time shocks on indirect drive implosion experiments. In a minor modification to the existing velocity interferometer system for any reflector diagnostic on NIF a fast-response vacuum photodiode was added to detect this light. The measurements show evidence of laser pre-pulse and possible light reflection off the hohlraum wall and onto the capsule.

Does the Sustainable PPI Investments Promote Financial Market’s Sustainable Development?

Directory of Open Access Journals (Sweden)

Tong Fu

2016-01-01

Full Text Available Since the late 1980s, most developing countries adopt a policy of attracting investments for Private Participation in Infrastructure (PPI projects. With a perspective of sustainability, this paper offers a first attempt to examine whether the sustainable PPI investments promote financial market development. First, we demonstrate how the PPI policy enlargers the size of financial markets and then fosters the liquidity of financial markets in the static and dynamic conditions. Using the data from 33 developing countries during 1997–2012, we discover the significant promotion effect of PPI investments on the development of financial markets in the dimensions of size and liquidity. Additionally, we confirm the significant mediator effect of financial market size for the positive relationship between PPI investments and financial market liquidity. Both the promotion effect and mediation effect are robust to different control variables and estimation techniques used.

SnO2/PPy Screen-Printed Multilayer CO2 Gas Sensor

Directory of Open Access Journals (Sweden)

S.A. WAGHULEY

2007-05-01

Full Text Available Tin dioxide (SnO2 plays a dominant role in solid state gas sensors and exhibit sensitivity towards oxidizing and reducing gases by a variation of its electrical properties. The electrical conducting polymer-polypyrrole (PPy has high anisotropy of electrical conduction and used as a gas sensor. SnO2/PPy multilayer, pure SnO2, pure PPy sensors were prepared by screen-printing method on Al2O3 layer followed by glass substrate. The sensors were used for different concentration (ppm of CO2 gas investigation at room temperature (303 K. The sensitivity of SnO2/PPy multilayer sensor was found to be higher, compared with pure SnO2 and pure PPy sensors. The multilayer sensor exhibited improved stability. The response and recovery time of multilayer sensor were found to be ~2 min and ~10 min respectively.

Hopping conduction on PPy/SiO2 nanocomposites obtained via in situ emulsion polymerization

NARCIS (Netherlands)

Rubinger, C.P.L.; Costa, L.C.; Carvalho Esteves, de A.C.; Barros-Timmons, A.M.M.V.

2008-01-01

This work describes the preparation and electrical characterization of conducting polypyrrole (PPy) and silica nanocomposites. Four samples were investigated: (i) pure PPy, (ii) PPy-covered SiO2 spherical nanoparticles, (iii) PPy-covered SiO2 spherical nanoparticles modified with

Protein complex detection in PPI networks based on data integration and supervised learning method.

Science.gov (United States)

Yu, Feng; Yang, Zhi; Hu, Xiao; Sun, Yuan; Lin, Hong; Wang, Jian

2015-01-01

Revealing protein complexes are important for understanding principles of cellular organization and function. High-throughput experimental techniques have produced a large amount of protein interactions, which makes it possible to predict protein complexes from protein-protein interaction (PPI) networks. However, the small amount of known physical interactions may limit protein complex detection. The new PPI networks are constructed by integrating PPI datasets with the large and readily available PPI data from biomedical literature, and then the less reliable PPI between two proteins are filtered out based on semantic similarity and topological similarity of the two proteins. Finally, the supervised learning protein complex detection (SLPC), which can make full use of the information of available known complexes, is applied to detect protein complex on the new PPI networks. The experimental results of SLPC on two different categories yeast PPI networks demonstrate effectiveness of the approach: compared with the original PPI networks, the best average improvements of 4.76, 6.81 and 15.75 percentage units in the F-score, accuracy and maximum matching ratio (MMR) are achieved respectively; compared with the denoising PPI networks, the best average improvements of 3.91, 4.61 and 12.10 percentage units in the F-score, accuracy and MMR are achieved respectively; compared with ClusterONE, the start-of the-art complex detection method, on the denoising extended PPI networks, the average improvements of 26.02 and 22.40 percentage units in the F-score and MMR are achieved respectively. The experimental results show that the performances of SLPC have a large improvement through integration of new receivable PPI data from biomedical literature into original PPI networks and denoising PPI networks. In addition, our protein complexes detection method can achieve better performance than ClusterONE.

Use of microsecond current prepulse for dramatic improvements of wire array Z-pinch implosion

International Nuclear Information System (INIS)

Calamy, H.; Lassalle, F.; Loyen, A.; Zucchini, F.; Chittenden, J. P.; Hamann, F.; Maury, P.; Georges, A.; Bedoch, J. P.; Morell, A.

2008-01-01

The Sphinx machine [F. Lassalle et al., 'Status on the SPHINX machine based on the 1microsecond LTD technology'] based on microsecond linear transformer driver (LTD) technology is used to implode an aluminium wire array with an outer diameter up to 140 mm and maximum current from 3.5 to 5 MA. 700 to 800 ns implosion Z-pinch experiments are performed on this driver essentially with aluminium. Best results obtained before the improvement described in this paper were 1-3 TW radial total power, 100-300 kJ total yield, and 20-30 kJ energy above 1 keV. An auxiliary generator was added to the Sphinx machine in order to allow a multi microsecond current to be injected through the wire array load before the start of the main current. Amplitude and duration of this current prepulse are adjustable, with maxima ∼10 kA and 50 μs. This prepulse dramatically changes the ablation phase leading to an improvement of the axial homogeneity of both the implosion and the final radiating column. Total power was multiplied by a factor of 6, total yield by a factor of 2.5 with a reproducible behavior. This paper presents experimental results, magnetohydrodynamic simulations, and analysis of the effect of such a long current prepulse

A Generalized Form of Context-Dependent Psychophysiological Interactions (gPPI): A Comparison to Standard Approaches

Science.gov (United States)

McLaren, Donald G.; Ries, Michele L.; Xu, Guofan; Johnson, Sterling C.

2012-01-01

Functional MRI (fMRI) allows one to study task-related regional responses and task-dependent connectivity analysis using psychophysiological interaction (PPI) methods. The latter affords the additional opportunity to understand how brain regions interact in a task-dependent manner. The current implementation of PPI in Statistical Parametric Mapping (SPM8) is configured primarily to assess connectivity differences between two task conditions, when in practice fMRI tasks frequently employ more than two conditions. Here we evaluate how a generalized form of context-dependent PPI (gPPI; http://www.nitrc.org/projects/gppi), which is configured to automatically accommodate more than two task conditions in the same PPI model by spanning the entire experimental space, compares to the standard implementation in SPM8. These comparisons are made using both simulations and an empirical dataset. In the simulated dataset, we compare the interaction beta estimates to their expected values and model fit using the Akaike Information Criterion (AIC). We found that interaction beta estimates in gPPI were robust to different simulated data models, were not different from the expected beta value, and had better model fits than when using standard PPI (sPPI) methods. In the empirical dataset, we compare the model fit of the gPPI approach to sPPI. We found that the gPPI approach improved model fit compared to sPPI. There were several regions that became non-significant with gPPI. These regions all showed significantly better model fits with gPPI. Also, there were several regions where task-dependent connectivity was only detected using gPPI methods, also with improved model fit. Regions that were detected with all methods had more similar model fits. These results suggest that gPPI may have greater sensitivity and specificity than standard implementation in SPM. This notion is tempered slightly as there is no gold standard; however, data simulations with a known outcome support our

Limited Effect of Rebamipide in Addition to Proton Pump Inhibitor (PPI) in the Treatment of Post-Endoscopic Submucosal Dissection Gastric Ulcers: A Randomized Controlled Trial Comparing PPI Plus Rebamipide Combination Therapy with PPI Monotherapy

OpenAIRE

Nakamura, Kazuhiko; Ihara, Eikichi; Akiho, Hirotada; Akahoshi, Kazuya; Harada, Naohiko; Ochiai, Toshiaki; Nakamura, Norimoto; Ogino, Haruei; Iwasa, Tsutomu; Aso, Akira; Iboshi, Yoichiro; Takayanagi, Ryoichi

2016-01-01

Background/Aims The ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy. Methods In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups recei...

PPI finder: a mining tool for human protein-protein interactions.

Directory of Open Access Journals (Sweden)

Min He

Full Text Available BACKGROUND: The exponential increase of published biomedical literature prompts the use of text mining tools to manage the information overload automatically. One of the most common applications is to mine protein-protein interactions (PPIs from PubMed abstracts. Currently, most tools in mining PPIs from literature are using co-occurrence-based approaches or rule-based approaches. Hybrid methods (frame-based approaches by combining these two methods may have better performance in predicting PPIs. However, the predicted PPIs from these methods are rarely evaluated by known PPI databases and co-occurred terms in Gene Ontology (GO database. METHODOLOGY/PRINCIPAL FINDINGS: We here developed a web-based tool, PPI Finder, to mine human PPIs from PubMed abstracts based on their co-occurrences and interaction words, followed by evidences in human PPI databases and shared terms in GO database. Only 28% of the co-occurred pairs in PubMed abstracts appeared in any of the commonly used human PPI databases (HPRD, BioGRID and BIND. On the other hand, of the known PPIs in HPRD, 69% showed co-occurrences in the literature, and 65% shared GO terms. CONCLUSIONS: PPI Finder provides a useful tool for biologists to uncover potential novel PPIs. It is freely accessible at http://liweilab.genetics.ac.cn/tm/.

The feasibility and application of PPy in cathodic polarization antifouling.

Science.gov (United States)

Jia, Meng-Yang; Zhang, Zhi-Ming; Yu, Liang-Min; Wang, Jia; Zheng, Tong-Tong

2018-04-01

Cathodic polarization antifouling deserves attention because of its environmentally friendly nature and good sustainability. It has been proven that cathodic voltages applied on metal substrates exhibit outstanding antifouling effects. However, most metals immersed in marine environment are protected by insulated anticorrosive coatings, restricting the cathodic polarization applied on metals. This study developed a conducting polypyrrole (PPy)/acrylic resin coating (σ = 0.18 Scm -1 ), which can be applied in cathodic polarization antifouling. The good stability and electro-activity of PPy in the negative polarity zone in alkalescent NaCl solution were verified by linear sweep voltammetry (LSV), chronoamperometry (CA), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), demonstrating the feasibility of PPy as cathodic polarization material. Furthermore, the antifouling effects of PPy/acrylicresin coating on 24-h old Escherichia coli bacteria (E. coli) which formed on PPy/acrylic resin-coated plastic plate were measured under different cathodic potentials and treatment time, characterized by fluorescent microscope. The results suggest that at cathodic potential around -0.5 V (vs. saturated calomel electrode (SCE)), there was little trace of attached bacteria on the substrate after 20 min of treatment. PPy/acrylicresin-coated substrates were also subjected to repeated cycles of biofilm formation and electrochemical removal, where high removal efficiencies were maintained throughout the total polarization process. Under these conditions, the generation of hydrogen peroxide is believed to be responsible for the antifouling effects because of causing oxidative damage to cells, suggesting the potential of the proposed technology for application on insulated surfaces in various industrial settings. Copyright © 2018 Elsevier B.V. All rights reserved.

Influence of disordered morphology on electrochromic stability of WO{sub 3}/PPy

Energy Technology Data Exchange (ETDEWEB)

Gaikwad, Digambar K. [D. Y. Patil College of Engineering & Technology, Kasaba Bawada, Kolhapur, 416006, Maharashtra (India); Mali, Sawanta S.; Hong, Chang K. [Polymer Energy Materials Laboratory, Department of Advanced Chemical Engineering, Chonnam National University, Gwangju, 500-757 (Korea, Republic of); Kadam, Anamika V., E-mail: anamikasonavane@rediff.com [D. Y. Patil College of Engineering & Technology, Kasaba Bawada, Kolhapur, 416006, Maharashtra (India); D.Y. Patil Medical University, Kasaba Bawada, Kolhapur, 416006, Maharashtra (India)

2016-06-05

Tungsten oxide (WO{sub 3}) films are critical for smart windows because of their capacity of varying the throughput of visible light and solar energy. This study highlights the evolution of structural and morphological changes of electrodeposited WO{sub 3} thin films coated with polypyrrole (PPy) by using chemical bath deposition. The structural and surface properties of WO{sub 3} thin films were studied using X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and transmission electron microscopy. The electrochemical stability was inspected using repetitive cyclic voltammetry (CV) cycles for each sample in LiClO{sub 4}-PC electrolyte for prolonged periods. The results showed an improvement in the electrochemical stability after the CV study. - Graphical abstract: Mechanism: A schematic of the mechanism is proposed in above fig. The mechanism is based on three step process: (i) WO{sub 3} coated on ITO by electrodeposition followed by thermal treatment. It produces ordered nanoarrayed morphology. (ii) A second step involving deposition of PPy by chemical bath deposition on ITO. It possesses globular morphology. (iii) When PPy coated on WO{sub 3}, PPy applies shearing force on WO{sub 3} and produces disordered nanoarrayed morphology. - Highlights: • Nanoarrayed WO{sub 3}/PPy composite was synthesized. • Interplanar spacing enhances due to PPy coating. • PPy applies shearing force on WO{sub 3} produces disordered morphology. • Nanocomposite showed high stability in LiClO{sub 4}-PC.

Electrochemomechanical constrained multiobjective optimization of PPy/MWCNT actuators

International Nuclear Information System (INIS)

Khalili, N; Naguib, H E; Kwon, R H

2014-01-01

Polypyrrole (PPy) conducting polymers have shown a great potential for the fabrication of conjugated polymer-based actuating devices. Consequently, they have been a key point in developing many advanced emerging applications such as biomedical devices and biomimetic robotics. When designing an actuator, taking all of the related decision variables, their roles and relationships into consideration is of pivotal importance to determine the actuator’s final performance. Therefore, the central focus of this study is to develop an electrochemomechanical constrained multiobjective optimization model of a PPy/MWCNTs trilayer actuator. For this purpose, the objective functions are designed to capture the three main characteristics of these actuators, namely their tip vertical displacement, blocking force and response time. To obtain the optimum range of the designated decision variables within the feasible domain, a multiobjective optimization algorithm is applied while appropriate constraints are imposed. The optimum points form a Pareto surface on which they are consistently spread. The numerical results are presented; these results enable one to design an actuator with consideration to the desired output performances. For the experimental analysis, a multilayer bending-type actuator is fabricated, which is composed of a PVDF layer and two layers of PPy with an incorporated layer of multi-walled carbon nanotubes deposited on each side of the PVDF membrane. The numerical results are experimentally verified; in order to determine the performance of the fabricated actuator, its outputs are compared with a neat PPy actuator’s experimental and numerical counterparts. (paper)

Increased sensorimotor gating in recreational and dependent cocaine users is modulated by craving and attention-deficit/hyperactivity disorder symptoms.

Science.gov (United States)

Preller, Katrin H; Ingold, Nina; Hulka, Lea M; Vonmoos, Matthias; Jenni, Daniela; Baumgartner, Markus R; Vollenweider, Franz X; Quednow, Boris B

2013-02-01

Cocaine dependence has been associated with blunted dopamine and norepinephrine signaling, but it is unknown if recreational cocaine use is also associated with alterations of catecholamine systems. Prepulse inhibition (PPI) of the acoustic startle response-a measure of sensorimotor gating-is highly sensitive for manipulations of the catecholamine system. Therefore, we investigated whether relatively pure recreational users (RCU) and dependent cocaine users (DCU) display alterations of PPI, startle reactivity, and habituation. Moreover, the influences of methylenedioxymethamphetamine and cannabis co-use, craving, and attention-deficit/hyperactivity disorder (ADHD) symptoms on startle measures were examined. In 64 RCU, 29 DCU, and 66 stimulant-naïve control subjects, PPI of acoustic startle response, startle reactivity, habituation, ADHD symptoms, and cocaine craving were assessed. Drug use of all participants was controlled by hair and urine toxicologies. Both RCU and DCU showed increased PPI in comparison with control participants (Cohen's d=.38 and d=.67, respectively), while RCU and DCU did not differ in PPI measures (d=.12). No significant group differences were found in startle reactivity or habituation measures. In cocaine users, PPI was positively correlated with cumulative cocaine dose used, craving for cocaine, and ADHD symptoms. Users with a diagnosis of ADHD and strong craving symptoms displayed the highest PPI levels compared with control subjects (d=.78). The augmented PPI in RCU and DCU suggests that recreational use of cocaine is associated with altered catecholamine signaling, in particular if ADHD or craving symptoms are present. Finally, ADHD might be a critical risk factor for cocaine-induced changes of the catecholamine system. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

HomPPI: a class of sequence homology based protein-protein interface prediction methods

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Dobbs Drena

2011-06-01

Full Text Available Abstract Background Although homology-based methods are among the most widely used methods for predicting the structure and function of proteins, the question as to whether interface sequence conservation can be effectively exploited in predicting protein-protein interfaces has been a subject of debate. Results We studied more than 300,000 pair-wise alignments of protein sequences from structurally characterized protein complexes, including both obligate and transient complexes. We identified sequence similarity criteria required for accurate homology-based inference of interface residues in a query protein sequence. Based on these analyses, we developed HomPPI, a class of sequence homology-based methods for predicting protein-protein interface residues. We present two variants of HomPPI: (i NPS-HomPPI (Non partner-specific HomPPI, which can be used to predict interface residues of a query protein in the absence of knowledge of the interaction partner; and (ii PS-HomPPI (Partner-specific HomPPI, which can be used to predict the interface residues of a query protein with a specific target protein. Our experiments on a benchmark dataset of obligate homodimeric complexes show that NPS-HomPPI can reliably predict protein-protein interface residues in a given protein, with an average correlation coefficient (CC of 0.76, sensitivity of 0.83, and specificity of 0.78, when sequence homologs of the query protein can be reliably identified. NPS-HomPPI also reliably predicts the interface residues of intrinsically disordered proteins. Our experiments suggest that NPS-HomPPI is competitive with several state-of-the-art interface prediction servers including those that exploit the structure of the query proteins. The partner-specific classifier, PS-HomPPI can, on a large dataset of transient complexes, predict the interface residues of a query protein with a specific target, with a CC of 0.65, sensitivity of 0.69, and specificity of 0.70, when homologs of

Sensorimotor Gating in Neurotensin-1 Receptor Null Mice

Science.gov (United States)

Feifel, D.; Pang, Z.; Shilling, P.D.; Melendez, G.; Schreiber, R.; Button, D.

2009-01-01

BACKGROUND Converging evidence has implicated endogenous neurotensin (NT) in the pathophysiology of brain processes relevant to schizophrenia. Prepulse inhibition of the startle reflex (PPI) is a measure of sensorimotor gating and considered to be of strong relevance to neuropsychiatric disorders associated with psychosis and cognitive dysfunction. Mice genetically engineered to not express NT display deficits in PPI that model the PPI deficits seen in schizophrenia patients. NT1 receptors have been most strongly implicated in mediating the psychosis relevant effects of NT such as attenuating PPI deficits. To investigate the role of NT1 receptors in the regulation of PPI, we measured baseline PPI in wildtype (WT) and NT1 knockout (KO) mice. We also tested the effects of amphetamine and dizocilpine, a dopamine agonist and NMDA antagonist, respectively, that reduce PPI as well as the NT1 selective receptor agonist, PD149163, known to increase PPI in rats. METHODS Baseline PPI and acoustic startle response were measured in WT and NT1 knockout KO mice. After baseline testing, mice were tested again after receiving intraperatoneal (IP) saline or one of three doses of amphetamine (1.0, 3.0 and 10.0 mg/kg), dizocilpine (0.3, 1.0 and 3.0 mg/kg) and PD149163 (0.5, 2.0 and 6.0 mg/kg) on separate test days. RESULTS Baseline PPI and acoustic startle response in NT1 KO mice were not significantly different from NT1 WT mice. WT and KO mice exhibited similar responses to the PPI-disrupting effects of dizocilpine and amphetamine. PD149163 significantly facilitated PPI (P < 0.004) and decreased the acoustic startle response (P < 0.001) in WT but not NT1 KO mice. CONCLUSIONS The data does not support the regulation of baseline PPI or the PPI disruptive effects of amphetamine or dizocilpine by endogenous NT acting at the NT1 receptor, although they support the antipsychotic potential of pharmacological activation of NT1 receptors by NT1 agonists. PMID:19596359

PpiA, a surface PPIase of the cyclophilin family in Lactococcus lactis.

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Nicolas Trémillon

Full Text Available BACKGROUND: Protein folding in the envelope is a crucial limiting step of protein export and secretion. In order to better understand this process in Lactococcus lactis, a lactic acid bacterium, genes encoding putative exported folding factors like Peptidyl Prolyl Isomerases (PPIases were searched for in lactococcal genomes. RESULTS: In L. lactis, a new putative membrane PPIase of the cyclophilin subfamily, PpiA, was identified and characterized. ppiA gene was found to be constitutively expressed under normal and stress (heat shock, H(2O(2 conditions. Under normal conditions, PpiA protein was synthesized and released from intact cells by an exogenously added protease, showing that it was exposed at the cell surface. No obvious phenotype could be associated to a ppiA mutant strain under several laboratory conditions including stress conditions, except a very low sensitivity to H(2O(2. Induction of a ppiA copy provided in trans had no effect i on the thermosensitivity of an mutant strain deficient for the lactococcal surface protease HtrA and ii on the secretion and stability on four exported proteins (a highly degraded hybrid protein and three heterologous secreted proteins in an otherwise wild-type strain background. However, a recombinant soluble form of PpiA that had been produced and secreted in L. lactis and purified from a culture supernatant displayed both PPIase and chaperone activities. CONCLUSIONS: Although L. lactis PpiA, a protein produced and exposed at the cell surface under normal conditions, displayed a very moderate role in vivo, it was found, as a recombinant soluble form, to be endowed with folding activities in vitro.

The effect of prepulse on x-ray laser development using a powerful subpicosecond KrF* laser

International Nuclear Information System (INIS)

Nam, C.H.; Tighe, W.; Valeo, E.; Suckewer, S.

1990-03-01

A high power uv laser has been developed as a pump source for short wavelength (down to 1 nm) x-ray lasers. Various schemes are considered and theoretical analysis is discussed. Spectroscopic studies of laser-target interaction have been performed and, in particular, the effect of a prepulse on plasma generation has been investigated. Analysis of the observed spectra indicates that reduction of the prepulse energy results in a higher temperature plasma. Investigation of the interaction using thin layered targets is also presented. These data provide evidence for initially hot plasma conditions generated from target layers ≤150 angstrom. Discussions of proposed laser schemes at 1-5 nm are presented. 45 refs., 8 figs., 1 tab

Association of Proton Pump Inhibitor (PPI Use with Energy Intake, Physical Activity, and Weight Gain

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Jennifer L. Czwornog

2015-10-01

Full Text Available Studies suggest proton pump inhibitor (PPI use impacts body weight regulation, though the effect of PPIs on energy intake, energy extraction, and energy expenditure is unknown. We used data on 3073 eligible adults from the National Health and Nutrition Examination Survey (NHANES. Medication use, energy intake, diet composition, and physical activity were extracted from NHANES. Multivariate regression models included confounding variables. Daily energy intake was similar between PPI users and non-users (p = 0.41. Diet composition was similar between the two groups, except that PPI users consumed a slightly greater proportion of calories from fat (34.5% vs. 33.2%; p = 0.02. PPI users rated themselves as being as physically active as their age/gender-matched peers and reported similar frequencies of walking or biking. However, PPI users were less likely to have participated in muscle-strengthening activities (OR: 0.53; 95% CI: 0.30–0.95. PPI users reported similar sedentary behaviors to non-users. Male PPI users had an increase in weight (of 1.52 ± 0.59 kg; p = 0.021 over the previous year compared to non-users, while female PPI users had a non-significant increase in weight. The potential mechanisms for PPI-associated weight gain are unclear as we did not find evidence for significant differences in energy intake or markers of energy expenditure.

Lamotrigine effects sensorimotor gating in WAG/Rij rats

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Ipek Komsuoglu Celikyurt

2012-01-01

Full Text Available Introduction: Prepulse inhibition (PPI is a measurable form of sensorimotor gating. Disruption of PPI reflects the impairment in the neural filtering process of mental functions that are related to the transformation of an external stimuli to a response. Impairment of PPI is reported in neuropsychiatric illnesses such as schizophrenia, Huntington′s disease, Parkinson′s diseases, Tourette syndrome, obsessive compulsive disorder, and temporal lobe epilepsy with psychosis. Absence epilepsy is the most common type of primary generalized epilepsy. Lamotrigine is an antiepileptic drug that is preferred in absence epilepsy and acts by stabilizing the voltage-gated sodium channels. Aim: In this study, we have compared WAG-Rij rats (genetically absence epileptic rats with Wistar rats, in order to clarify if there is a deficient sensorimotor gating in absence epilepsy, and have examined the effects of lamotrigine (15, 30 mg/kg, i.p. on this phenomenon. Materials and Methods: Depletion in PPI percent value is accepted as a disruption in sensory-motor filtration function. The difference between the Wistar and WAG/Rij rats has been evaluated with the student t test and the effects of lamotrigine on the PPI percent have been evaluated by the analysis of variance (ANOVA post-hoc Dunnett′s test. Results: The PPI percent was low in the WAG/Rij rats compared to the controls (P<0.0001, t:9,612. Although the PPI percent value of the control rats was not influenced by lamotrigine, the PPI percent value of the WAG/Rij rats was raised by lamotrigine treatment (P<0.0001, F:861,24. Conclusions: As a result of our study, PPI was disrupted in the WAG/Rij rats and this disruption could be reversed by an antiepileptic lamotrigine.

77 FR 76303 - Notice of Availability of Producer Price Index (PPI) Data Users Survey

Science.gov (United States)

2012-12-27

...) Data Users Survey AGENCY: Bureau of Labor Statistics, Labor. ACTION: Notice of availability of survey... Index (PPI) data users. The survey is necessary to: Identify PPI data users, see how they use our data... conducted a survey of PPI data users in late 1976 through early 1977. Since that time, numerous new time...

Photocurrent and photothermal current of polypyrrole (PPy) film

Energy Technology Data Exchange (ETDEWEB)

Zhao Chongjun; Wang Haihong; Jiang Zhiyu

2003-02-28

The photoelectrochemical properties of polypyrrole (PPy) film in aqueous solutions in the potential region of -0.7 to 0.5 V (versus Ag/AgCl) were investigated by using photocurrent, photothermal and photothermal current methods under the irradiation of laser beams with wavelength of 532 and 632.8 nm, respectively. It was found that the photocurrent at more negative potential was caused by the p-type semiconductor properties, while the photocurrent at more positive potential was caused by the local temperature rather than the semiconductor properties of the films. The effect of the film thickness on the photocurrent of PPy films was studied in detail.

Photocurrent and photothermal current of polypyrrole (PPy) film

International Nuclear Information System (INIS)

Zhao Chongjun; Wang Haihong; Jiang Zhiyu

2003-01-01

The photoelectrochemical properties of polypyrrole (PPy) film in aqueous solutions in the potential region of -0.7 to 0.5 V (versus Ag/AgCl) were investigated by using photocurrent, photothermal and photothermal current methods under the irradiation of laser beams with wavelength of 532 and 632.8 nm, respectively. It was found that the photocurrent at more negative potential was caused by the p-type semiconductor properties, while the photocurrent at more positive potential was caused by the local temperature rather than the semiconductor properties of the films. The effect of the film thickness on the photocurrent of PPy films was studied in detail

Sex differences and serotonergic mechanisms in the behavioural effects of psilocin.

Science.gov (United States)

Tylš, Filip; Páleníček, Tomáš; Kadeřábek, Lukáš; Lipski, Michaela; Kubešová, Anna; Horáček, Jiří

2016-06-01

Psilocybin has recently attracted a great deal of attention as a clinical research and therapeutic tool. The aim of this paper is to bridge two major knowledge gaps regarding its behavioural pharmacology - sex differences and the underlying receptor mechanisms. We used psilocin (0.25, 1 and 4 mg/kg), an active metabolite of psilocybin, in two behavioural paradigms - the open-field test and prepulse inhibition (PPI) of the acoustic startle reaction. Sex differences were evaluated with respect to the phase of the female cycle. The contribution of serotonin receptors in the behavioural action was tested in male rats with selective serotonin receptor antagonists: 5-HT1A receptor antagonist (WAY100635 1 mg/kg), 5-HT2A receptor antagonist (MDL100907 0.5 mg/kg), 5-HT2B receptor antagonist (SB215505 1 mg/kg) and 5-HT2C receptor antagonist (SB242084 1 mg/kg). Psilocin induced dose-dependent inhibition of locomotion and suppression of normal behaviour in rats (behavioural serotonin syndrome, impaired PPI). The effects were more pronounced in male rats than in females. The inhibition of locomotion was normalized by 5-HT1A and 5-HT2B/C antagonists; however, PPI was not affected significantly by these antagonists. Our findings highlight an important issue of sex-specific reactions to psilocin and that apart from 5-HT2A-mediated effects 5-HT1A and 5-HT2C/B receptors also play an important role. These findings have implications for recent clinical trials.

Super high precision 200 ppi liquid crystal display series; Chokoseido 200 ppi ekisho display series

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-03-01

In mobile equipment, in demand is a high precision liquid crystal display (LCD) having the power of expression equivalent to printed materials like magazines because of the necessity of displaying a large amount of information on a easily potable small screen. In addition, with the spread and high-quality image of digital still cameras, it is strongly desired to display photographed digital image data in high quality. Toshiba Corp., by low temperature polysilicone (p-Si) technology, commercialized the liquid crystal display series of 200 ppi (pixels per inch) precision dealing with the rise of the high-precision high-image quality LCD market. The super high precision of 200 ppi enables the display of smooth beautiful animation comparable to printed sheets of magazines and photographs. The display series are suitable for the display of various information services such as electronic books and electronic photo-viewers including internet. The screen sizes lined up are No. 4 type VGA (640x480 pixels) of a small pocket notebook size and No. 6.3 type XGA (1,024x768 pixels) of a paperback size, with a larger screen to be furthered. (translated by NEDO)

Enduring sensorimotor gating abnormalities following predator exposure or corticotropin-releasing factor in rats: a model for PTSD-like information-processing deficits?

Science.gov (United States)

Bakshi, Vaishali P; Alsene, Karen M; Roseboom, Patrick H; Connors, Elenora E

2012-02-01

A deficit in prepulse inhibition (PPI) can be one of the clinically observed features of post-traumatic stress disorder (PTSD) that is seen long after the acute traumatic episode has terminated. Thus, reduced PPI may represent an enduring psychophysiological marker of this illness in some patients. PPI is an operational measure of sensorimotor gating and refers to the phenomenon in which a weak stimulus presented immediately before an intense startling stimulus inhibits the magnitude of the subsequent startle response. The effects of stress on PPI have been relatively understudied, and in particular, there is very little information on PPI effects of ethologically relevant psychological stressors. We aimed to develop a paradigm for evaluating stress-induced sensorimotor gating abnormalities by comparing the effects of a purely psychological stressor (predator exposure) to those of a nociceptive physical stressor (footshock) on PPI and baseline startle responses in rats over an extended period of time following stressor presentation. Male Sprague-Dawley rats were exposed (within a protective cage) to ferrets for 5 min or left in their homecage and then tested for PPI immediately, 24 h, 48 h, and 9 days after the exposure. The effects of footshock were evaluated in a separate set of rats. The effects seen with stressor presentation were compared to those elicited by corticotropin-releasing factor (CRF; 0.5 and 3 μg/6 μl, intracerebroventricularly). Finally, the effects of these stressors and CRF administration on plasma corticosterone were measured. PPI was disrupted 24 h after ferret exposure; in contrast, footshock failed to affect PPI at any time. CRF mimicked the predator stress profile, with the lowdose producing a PPI deficit 24 h after infusion. Interestingly, the high dose also produced a PPI deficit 24 h after infusion, but with this dose, the PPI deficit was evident even 9d later. Plasma corticosterone levels were elevated acutely (before PPI deficits

Easily fabricated and lightweight PPy/PDA/AgNW composites for excellent electromagnetic interference shielding.

Science.gov (United States)

Wang, Yan; Gu, Fu-Qiang; Ni, Li-Juan; Liang, Kun; Marcus, Kyle; Liu, Shu-Li; Yang, Fan; Chen, Jin-Ju; Feng, Zhe-Sheng

2017-11-30

Conductive polymer composites (CPCs) containing nanoscale conductive fillers have been widely studied for their potential use in various applications. In this paper, polypyrrole (PPy)/polydopamine (PDA)/silver nanowire (AgNW) composites with high electromagnetic interference (EMI) shielding performance, good adhesion ability and light weight are successfully fabricated via a simple in situ polymerization method followed by a mixture process. Benefiting from the intrinsic adhesion properties of PDA, the adhesion ability and mechanical properties of the PPy/PDA/AgNW composites are significantly improved. The incorporation of AgNWs endows the functionalized PPy with tunable electrical conductivity and enhanced EMI shielding effectiveness (SE). By adjusting the AgNW loading degree in the PPy/PDA/AgNW composites from 0 to 50 wt%, the electrical conductivity of the composites greatly increases from 0.01 to 1206.72 S cm -1 , and the EMI SE of the composites changes from 6.5 to 48.4 dB accordingly (8.0-12.0 GHz, X-band). Moreover, due to the extremely low density of PPy, the PPy/PDA/AgNW (20 wt%) composites show a superior light weight of 0.28 g cm -3 . In general, it can be concluded that the PPy/PDA/AgNW composites with tunable electrical conductivity, good adhesion properties and light weight can be used as excellent EMI shielding materials.

Developmental vitamin D deficiency alters MK 801-induced hyperlocomotion in the adult rat: An animal model of schizophrenia.

Science.gov (United States)

Kesby, James P; Burne, Thomas H J; McGrath, John J; Eyles, Darryl W

2006-09-15

Developmental vitamin D (DVD) deficiency has been proposed as a risk factor for schizophrenia. The behavioral phenotype of adult rats subjected to transient low prenatal vitamin D is characterized by spontaneous hyperlocomotion but normal prepulse inhibition of acoustic startle (PPI). The aim of this study was to examine the impact of selected psychotropic agents and one well-known antipsychotic agent on the behavioral phenotype of DVD deplete rats. Control versus DVD deplete adult rats were assessed on holeboard, open field and PPI. In the open field, animals were given MK-801 and/or haloperidol. For PPI, the animals were given apomorphine or MK-801. DVD deplete rats had increased baseline locomotion on the holeboard task and increased locomotion in response to MK-801 compared to control rats. At low doses, haloperidol antagonized the MK-801 hyperactivity of DVD deplete rats preferentially and, at a high dose, resulted in a more pronounced reduction in spontaneous locomotion in DVD deplete rats. DVD depletion did not affect either baseline or drug-mediated PPI response. These results suggest that DVD deficiency is associated with a persistent alteration in neuronal systems associated with motor function but not those associated with sensory motor gating. In light of the putative association between low prenatal vitamin D and schizophrenia, the discrete behavioral differences associated with the DVD model may help elucidate the neurobiological correlates of schizophrenia.

Nicotine ameliorates schizophrenia-like cognitive deficits induced by maternal LPS exposure: a study in rats

Directory of Open Access Journals (Sweden)

Uta Waterhouse

2016-10-01

Full Text Available Maternal exposure to infectious agents is a predisposing factor for schizophrenia with associated cognitive deficits in offspring. A high incidence of smoking in these individuals in adulthood might be, at least in part, due to the cognitive-enhancing effects of nicotine. Here, we have used prenatal exposure to maternal lipopolysaccharide (LPS, bacterial endotoxin at different time points as a model for cognitive deficits in schizophrenia to determine whether nicotine reverses any associated impairments. Pregnant rats were treated subcutaneously with LPS (0.5 mg/kg at one of three neurodevelopmental time periods [gestation days (GD 10-11, 15-16, 18-19]. Cognitive assessment in male offspring commenced in early adulthood [postnatal day (PND 60] and included: prepulse inhibition (PPI, latent inhibition (LI and delayed non-matching to sample (DNMTS. Following PND 100, daily nicotine injections (0.6 mg/kg, subcutaneously were administered, and animals were re-tested in the same tasks (PND 110. Only maternal LPS exposure early during fetal neurodevelopment (GD 10-11 resulted in deficits in all tests compared to animals that had been prenatally exposed to saline at the same gestational time point. Repeated nicotine treatment led to global (PPI and selective (LI improvements in performance. Early but not later prenatal LPS exposure induced consistent deficits in cognitive tests with relevance for schizophrenia. Nicotine reversed the LPS-induced deficits in selective attention (LI and induced a global enhancement of sensorimotor gating (PPI.

Safety of long-term PPI therapy

DEFF Research Database (Denmark)

Reimer, Christina

2013-01-01

Proton pump inhibitors have become the mainstay of medical treatment of acid-related disorders. Long-term use is becoming increasingly common, in some cases without a proper indication. A large number of mainly observational studies on a very wide range of possible associations have been publishe...... to a careful evaluation of the indication for PPI treatment....

Neonatal disruption of serine racemase causes schizophrenia-like behavioral abnormalities in adulthood: clinical rescue by d-serine.

Directory of Open Access Journals (Sweden)

Hiroko Hagiwara

Full Text Available D-Serine, an endogenous co-agonist of the N-methyl-D-aspartate (NMDA receptor, is synthesized from L-serine by serine racemase (SRR. Given the role of D-serine in both neurodevelopment and the pathophysiology of schizophrenia, we examined whether neonatal disruption of D-serine synthesis by SRR inhibition could induce behavioral abnormalities relevant to schizophrenia, in later life.Neonatal mice (7-9 days were injected with vehicle or phenazine methosulfate (Met-Phen: 3 mg/kg/day, an SRR inhibitor. Behavioral evaluations, such as spontaneous locomotion, novel object recognition test (NORT, and prepulse inhibition (PPI were performed at juvenile (5-6 weeks old and adult (10-12 weeks old stages. In addition, we tested the effects of D-serine on PPI deficits in adult mice after neonatal Met-Phen exposure. Finally, we assessed whether D-serine could prevent the onset of schizophrenia-like behavior in these mice. Neonatal Met-Phen treatment reduced D-serine levels in the brain, 24 hours after the final dose. Additionally, this treatment caused behavioral abnormalities relevant to prodromal symptoms in juveniles and to schizophrenia in adults. A single dose of D-serine improved PPI deficits in adult mice. Interestingly, chronic administration of D-serine (900 mg/kg/day from P35 to P70 significantly prevented the onset of PPI deficits after neonatal Met-Phen exposure.This study shows that disruption of D-serine synthesis during developmental stages leads to behavioral abnormalities relevant to prodromal symptoms and schizophrenia, in later life. Furthermore, early pharmacological intervention with D-serine may prevent the onset of psychosis in adult.

Electrochemical Behaviour of a PPy(DBS)/Polyacrylonitrile (PAN):LITF:EC:PC/ Li Cell

DEFF Research Database (Denmark)

Vidanapathirana, K.; Careem, M.A.; Skaarup, Steen

2006-01-01

The electrochemical behaviour of Li rechargeable cells with Polypyrrole (PPy) as the cathode material was investigated using cyclic voltammetry. The PPy used was doped with the large surfactant anion dodecyl benzenesulphonate (DBS-). The cells were constructed with PAN:LiTF:EC:PC gel electrolyte...... with Li as anode. The results indicate that during the first reduction, cations are inserted into the PPy film forming LiDBS neutral salt. During the next oxidation/reduction cycles, the mechanism then switches to anion movement. Cyclic voltammetry studies also verified that complete electrochemical...

Disrupted sensory gating in pathological gambling.

Science.gov (United States)

Stojanov, Wendy; Karayanidis, Frini; Johnston, Patrick; Bailey, Andrew; Carr, Vaughan; Schall, Ulrich

2003-08-15

Some neurochemical evidence as well as recent studies on molecular genetics suggest that pathologic gambling may be related to dysregulated dopamine neurotransmission. The current study examined sensory (motor) gating in pathologic gamblers as a putative measure of endogenous brain dopamine activity with prepulse inhibition of the acoustic startle eye-blink response and the auditory P300 event-related potential. Seventeen pathologic gamblers and 21 age- and gender-matched healthy control subjects were assessed. Both prepulse inhibition measures were recorded under passive listening and two-tone prepulse discrimination conditions. Compared to the control group, pathologic gamblers exhibited disrupted sensory (motor) gating on all measures of prepulse inhibition. Sensory motor gating deficits of eye-blink responses were most profound at 120-millisecond prepulse lead intervals in the passive listening task and at 240-millisecond prepulse lead intervals in the two-tone prepulse discrimination task. Sensory gating of P300 was also impaired in pathologic gamblers, particularly at 500-millisecond lead intervals, when performing the discrimination task on the prepulse. In the context of preclinical studies on the disruptive effects of dopamine agonists on prepulse inhibition, our findings suggest increased endogenous brain dopamine activity in pathologic gambling in line with previous neurobiological findings.

Feasibility of MR Imaging/MR Spectroscopy-Planned Focal Partial Salvage Permanent Prostate Implant (PPI) for Localized Recurrence After Initial PPI for Prostate Cancer

International Nuclear Information System (INIS)

Hsu, Charles C.; Hsu, Howard; Pickett, Barby; Crehange, Gilles; Hsu, I-Chow Joe; Dea, Ryan; Weinberg, Vivian; Gottschalk, Alexander R.; Kurhanewicz, John; Shinohara, Katsuto; Roach, Mack

2013-01-01

Purpose: To assess the feasibility of magnetic resonance imaging (MRI)-planned partial salvage permanent prostate implant (psPPI) among patients with biopsy-proven local recurrence after initial PPI without evidence of distant disease. Methods and Materials: From 2003-2009, 15 patients underwent MRI/magnetic resonance spectroscopy (MRS) planning for salvage brachytherapy (psPPI, I-125 [n=14; 144 Gy]; Pd-103 [n=1; 125 Gy]) without hormone therapy. Full dose was prescribed to areas of recurrence and underdosage, without entire prostate implantation. Limiting urethral and rectal toxicity was prioritized. Follow-up was from salvage date to prostate-specific antigen (PSA) concentration failure (Phoenix criteria = nadir + 2.0; ASTRO = 3 consecutive rises), recurrence, distant metastases, or last follow-up PSA level. Progression-free survival (PFS) was defined as no PSA failure or biopsy-proven recurrence without all-cause mortality. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Results: At salvage, median age was 68 years, and PSA concentration was 3.5 ng/mL (range, 0.9-5.6 ng/mL). Abnormal MRI/MRS findings were evident in 40% of patients. Biopsy-proven recurrences consisted of a single focus (80%) or 2 foci (20%). At recurrence, Gleason score was 6 (67%) or ≥7 (27%). Median interval between initial and salvage implantation was 69 months (range, 28-132 months). psPPI planning characteristics limited doses to the rectum (mean V100 = 0.5% [0.07 cc]) and urethra (V100 = 12% [0.3 cc]). At median follow-up (23.3 months; range, 8-88 months), treatment failure (n=2) resulted only in localized recurrence; both patients underwent second psPPI with follow-up PSA tests at 12 and 26 months, resulting in 0.6 and 0.7 ng/mL, respectively. American Society for Radiation Oncology PFS rates at 1, 2, and 3 years were 86.7%, 78.4%, and 62.7%, respectively, with 5 patients for whom treatment failed (n=3 with negative transrectal ultrasound

Feasibility of MR Imaging/MR Spectroscopy-Planned Focal Partial Salvage Permanent Prostate Implant (PPI) for Localized Recurrence After Initial PPI for Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Hsu, Charles C., E-mail: hsucc@radonc.ucsf.edu [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Hsu, Howard [Department of Radiation Oncology, New York University, New York, New York (United States); Pickett, Barby [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Crehange, Gilles [Department of Radiation Oncology, Dijon University, Dijon (France); Hsu, I-Chow Joe; Dea, Ryan [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Weinberg, Vivian [Biostatistics and Computational Biology Core, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Gottschalk, Alexander R. [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Kurhanewicz, John [Department of Radiology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Shinohara, Katsuto [Department of Urology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Roach, Mack [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States)

2013-02-01

Purpose: To assess the feasibility of magnetic resonance imaging (MRI)-planned partial salvage permanent prostate implant (psPPI) among patients with biopsy-proven local recurrence after initial PPI without evidence of distant disease. Methods and Materials: From 2003-2009, 15 patients underwent MRI/magnetic resonance spectroscopy (MRS) planning for salvage brachytherapy (psPPI, I-125 [n=14; 144 Gy]; Pd-103 [n=1; 125 Gy]) without hormone therapy. Full dose was prescribed to areas of recurrence and underdosage, without entire prostate implantation. Limiting urethral and rectal toxicity was prioritized. Follow-up was from salvage date to prostate-specific antigen (PSA) concentration failure (Phoenix criteria = nadir + 2.0; ASTRO = 3 consecutive rises), recurrence, distant metastases, or last follow-up PSA level. Progression-free survival (PFS) was defined as no PSA failure or biopsy-proven recurrence without all-cause mortality. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Results: At salvage, median age was 68 years, and PSA concentration was 3.5 ng/mL (range, 0.9-5.6 ng/mL). Abnormal MRI/MRS findings were evident in 40% of patients. Biopsy-proven recurrences consisted of a single focus (80%) or 2 foci (20%). At recurrence, Gleason score was 6 (67%) or {>=}7 (27%). Median interval between initial and salvage implantation was 69 months (range, 28-132 months). psPPI planning characteristics limited doses to the rectum (mean V100 = 0.5% [0.07 cc]) and urethra (V100 = 12% [0.3 cc]). At median follow-up (23.3 months; range, 8-88 months), treatment failure (n=2) resulted only in localized recurrence; both patients underwent second psPPI with follow-up PSA tests at 12 and 26 months, resulting in 0.6 and 0.7 ng/mL, respectively. American Society for Radiation Oncology PFS rates at 1, 2, and 3 years were 86.7%, 78.4%, and 62.7%, respectively, with 5 patients for whom treatment failed (n=3 with negative transrectal ultrasound

A patient and public involvement (PPI) toolkit for meaningful and flexible involvement in clinical trials - a work in progress.

Science.gov (United States)

Bagley, Heather J; Short, Hannah; Harman, Nicola L; Hickey, Helen R; Gamble, Carrol L; Woolfall, Kerry; Young, Bridget; Williamson, Paula R

2016-01-01

Funders of research are increasingly requiring researchers to involve patients and the public in their research. Patient and public involvement (PPI) in research can potentially help researchers make sure that the design of their research is relevant, that it is participant friendly and ethically sound. Using and sharing PPI resources can benefit those involved in undertaking PPI, but existing PPI resources are not used consistently and this can lead to duplication of effort. This paper describes how we are developing a toolkit to support clinical trials teams in a clinical trials unit. The toolkit will provide a key 'off the shelf' resource to support trial teams with limited resources, in undertaking PPI. Key activities in further developing and maintaining the toolkit are to: ● listen to the views and experience of both research teams and patient and public contributors who use the tools; ● modify the tools based on our experience of using them; ● identify the need for future tools; ● update the toolkit based on any newly identified resources that come to light; ● raise awareness of the toolkit and ● work in collaboration with others to either develop or test out PPI resources in order to reduce duplication of work in PPI. Background Patient and public involvement (PPI) in research is increasingly a funder requirement due to the potential benefits in the design of relevant, participant friendly, ethically sound research. The use and sharing of resources can benefit PPI, but available resources are not consistently used leading to duplication of effort. This paper describes a developing toolkit to support clinical trials teams to undertake effective and meaningful PPI. Methods The first phase in developing the toolkit was to describe which PPI activities should be considered in the pathway of a clinical trial and at what stage these activities should take place. This pathway was informed through review of the type and timing of PPI activities within

Surprising volume change in PPy(DBS): An atomic force microscopy study

DEFF Research Database (Denmark)

Smela, E.; Gadegaard, N.

1999-01-01

Communication: Conjugated polymers such as polypyrrole (PPy) have potential use as artificial muscles or in microsystems such as valves for micro-fluid handling. One of the most important parameters in such uses is the magnitude of volume change during associated redox processes; however, until now...... estimates have varied greatly. Atomic force microscopy is reported here as allowing direct measurement of the in situ thickness change during oxidation and reduction of thin films of PPy doped with dodecylbenzenesulfonate....

Femtosecond laser-plasma interaction with prepulse-generated liquid metal microjets

International Nuclear Information System (INIS)

Uryupina, D. S.; Ivanov, K. A.; Savel'ev, A. B.; Volkov, R. V.; Brantov, A. V.; Bychenkov, V. Yu.; Povarnitsyn, M. E.; Tikhonchuk, V. T.

2012-01-01

Ultrashort laser pulse interaction with a microstructured surface of a melted metal is a promising source of hard x-ray radiation. Microstructuring is achieved by a weak prepulse that produces narrow high-density microjets. As an x-ray source, the interaction of the main laser pulse with such jets is shown to be nearly two orders of magnitude more efficient than the interaction with ordinary metal targets. This paper presents the results of optical and x-ray studies of laser-plasma interaction physics under such conditions supported by numerical simulations of microjet formation and fast-electron generation.

Femtosecond laser-plasma interaction with prepulse-generated liquid metal microjets

Energy Technology Data Exchange (ETDEWEB)

Uryupina, D. S.; Ivanov, K. A.; Savel' ev, A. B.; Volkov, R. V. [Faculty of Physics and International Laser Center of M.V. Lomonosov Moscow State University, 119991 Moscow, Leninskie Gory (Russian Federation); Brantov, A. V.; Bychenkov, V. Yu. [P. N. Lebedev Physical Institute, Russian Academy of Sciences, 119991 Moscow (Russian Federation); Povarnitsyn, M. E. [Joint Institute for High Temperatures, Russian Academy of Sciences, 125412 Moscow (Russian Federation); Tikhonchuk, V. T. [CELIA, University of Bordeaux - CNRS - CEA, 33405 Talence (France)

2012-01-15

Ultrashort laser pulse interaction with a microstructured surface of a melted metal is a promising source of hard x-ray radiation. Microstructuring is achieved by a weak prepulse that produces narrow high-density microjets. As an x-ray source, the interaction of the main laser pulse with such jets is shown to be nearly two orders of magnitude more efficient than the interaction with ordinary metal targets. This paper presents the results of optical and x-ray studies of laser-plasma interaction physics under such conditions supported by numerical simulations of microjet formation and fast-electron generation.

Polypyrrole-poly(3,4-ethylenedioxythiophene)-Ag (PPy-PEDOT-Ag) nanocomposite films for label-free electrochemical DNA sensing.

Science.gov (United States)

Radhakrishnan, S; Sumathi, C; Umar, Ahmad; Jae Kim, Sang; Wilson, J; Dharuman, V

2013-09-15

The electrochemical DNA hybridization sensing of bipolymer polypyrrole and poly(3,4-ethylenedioxythiophene) (PPy-PEDOT) nanotubes functionalized with Ag nanoparticles has been investigated. The bipolymer nanotubes are prepared by simple chemical route and silver nanoparticles (Ag) further deposited over the PPy-PEDOT nanotubes to form PPy-PEDOT-Ag nanocomposite films. DNA labeled at 5'end using 6-mercapto-1-hexhane (HS-ssDNA) is immobilized on the PPy-PEDOT-Ag surface to form PPy-PEDOT-Ag-S-ssDNA and hybridization sensing is done in phosphate buffer. The presence of Ag nanoparticles (~28±5nm) well dispersed in the polymer composite with high surface area, high electrical conductivity and catalytic activity provides desirable microenvironment for the immobilization of probe DNA with controlled orientation leading to increased hybridization efficiency with target DNA. The morphological and structural characterizations by a scanning electron microscope (SEM) and X-ray diffraction (XRD) confirm the nanotube structure of composite polymer while Raman measurements indicate the efficient interactions between the PPy, PEDOT, Ag and HS-ssDNA. The sensor effectively discriminates different target DNA sequences with PPy-PEDOT-Ag-S-ssDNA substrate. The observed dynamic detection range is found between 1×10(-11)M and 1×10(-14)M with the lowest detection limit (3 σ/b) of 5.4×10(-15)M. This observed value is of higher sensitivity than that for MWCNT-Ag, PANi-Au, MWCNT-PPy-Au and PPy-PANi-Au composites reported previously. Copyright © 2013 Elsevier B.V. All rights reserved.

Spatial hearing ability of the pigmented Guinea pig (Cavia porcellus): Minimum audible angle and spatial release from masking in azimuth.

Science.gov (United States)

Greene, Nathaniel T; Anbuhl, Kelsey L; Ferber, Alexander T; DeGuzman, Marisa; Allen, Paul D; Tollin, Daniel J

2018-08-01

Despite the common use of guinea pigs in investigations of the neural mechanisms of binaural and spatial hearing, their behavioral capabilities in spatial hearing tasks have surprisingly not been thoroughly investigated. To begin to fill this void, we tested the spatial hearing of adult male guinea pigs in several experiments using a paradigm based on the prepulse inhibition (PPI) of the acoustic startle response. In the first experiment, we presented continuous broadband noise from one speaker location and switched to a second speaker location (the "prepulse") along the azimuth prior to presenting a brief, ∼110 dB SPL startle-eliciting stimulus. We found that the startle response amplitude was systematically reduced for larger changes in speaker swap angle (i.e., greater PPI), indicating that using the speaker "swap" paradigm is sufficient to assess stimulus detection of spatially separated sounds. In a second set of experiments, we swapped low- and high-pass noise across the midline to estimate their ability to utilize interaural time- and level-difference cues, respectively. The results reveal that guinea pigs can utilize both binaural cues to discriminate azimuthal sound sources. A third set of experiments examined spatial release from masking using a continuous broadband noise masker and a broadband chirp signal, both presented concurrently at various speaker locations. In general, animals displayed an increase in startle amplitude (i.e., lower PPI) when the masker was presented at speaker locations near that of the chirp signal, and reduced startle amplitudes (increased PPI) indicating lower detection thresholds when the noise was presented from more distant speaker locations. In summary, these results indicate that guinea pigs can: 1) discriminate changes in source location within a hemifield as well as across the midline, 2) discriminate sources of low- and high-pass sounds, demonstrating that they can effectively utilize both low-frequency interaural

A review on comparative study of PPI and PAMAM dendrimers

International Nuclear Information System (INIS)

Kaur, Daljeet; Jain, Keerti; Mehra, Neelesh Kumar; Kesharwani, Prashant; Jain, Narendra K.

2016-01-01

Dendrimers are hyperbranched, monodispersed macromolecules with multivalent functional end groups. Dendrimers have been explored as carrier for many drugs like anticancer, antiviral, antimalarial, antiprotozoal, anti tubercular drugs. Although a number of different types of dendrimers containing different core molecules, branching monomers and surface functional groups have been designed till date for drug delivery applications, yet the poly(propyleneimine) (PPI) and poly(amidoamine) (PAMAM) dendrimers have been the most explored dendrimers in this regard. In this review, we have summarized a comparative data on PPI and PAMAM dendrimers particularly relevant to their properties, synthesis, toxicity, biomedical applications and drug delivery attributes.

A review on comparative study of PPI and PAMAM dendrimers

Energy Technology Data Exchange (ETDEWEB)

Kaur, Daljeet; Jain, Keerti, E-mail: keertijain02@gmail.com; Mehra, Neelesh Kumar [ISF College of Pharmacy, Pharmaceutical Nanotechnology Research Laboratory (India); Kesharwani, Prashant [Wayne State University, Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences (United States); Jain, Narendra K., E-mail: jnarendr@yahoo.co.in, E-mail: dr.jnarendr@gmail.com [ISF College of Pharmacy, Pharmaceutical Nanotechnology Research Laboratory (India)

2016-06-15

Dendrimers are hyperbranched, monodispersed macromolecules with multivalent functional end groups. Dendrimers have been explored as carrier for many drugs like anticancer, antiviral, antimalarial, antiprotozoal, anti tubercular drugs. Although a number of different types of dendrimers containing different core molecules, branching monomers and surface functional groups have been designed till date for drug delivery applications, yet the poly(propyleneimine) (PPI) and poly(amidoamine) (PAMAM) dendrimers have been the most explored dendrimers in this regard. In this review, we have summarized a comparative data on PPI and PAMAM dendrimers particularly relevant to their properties, synthesis, toxicity, biomedical applications and drug delivery attributes.

Structural and electrochemical studies of PPy/PEG-LiFePO4 cathode material for Li-ion batteries

International Nuclear Information System (INIS)

Fedorkova, Andrea; Nacher-Alejos, Ana; Gomez-Romero, Pedro; Orinakova, Renata; Kaniansky, Dusan

2010-01-01

A simple chemical oxidative polymerization of pyrrole (Py) directly onto the surface of LiFePO 4 particles was applied to the synthesis of polypyrrole-LiFePO 4 (PPy-LiFePO 4 ) powder. The LiFePO 4 sample without carbon coating was synthesized by a solvothermal method. The polyethylene glycol (PEG) was used as additive during Py polymerization for increasing the PPy-LiFePO 4 conductivity. Properties of resulting LiFePO 4 , PPy-LiFePO 4 and PPy/PEG-LiFePO 4 samples were characterized by XRD, SEM, TGA and galvanostatic charge-discharge measurements. These methods confirmed the presence of polypyrrole on LiFePO 4 particles and its homogeneous distribution in the resulting powder material. The PPy/PEG-LiFePO 4 composites show higher discharge capacity than pure LiFePO 4 , as PPy/PEG network improves the electron conductivity. It presents specific discharge capacity of 153 mAh/g at C/5 rate.

Control of laser-beam propagation and absorption in a nanoplasma gas by programming of a transient complex refractive index with a prepulse

International Nuclear Information System (INIS)

Chu, H.-E.; Xiao, Y.-F.; Tsai, H.-E.; Lee, C.-H.; Lin, J.-Y.; Wang, J.; Chen, S.-Y.

2004-01-01

By utilizing the intensity- and duration-dependent heating and expansion rate of nanoplasma to generate a transient transverse gradient of the refractive index, prepulse controlled laser-beam propagation is demonstrated. The dynamical response of the macroscopic optical refractive index is traced back to the microscopic polarizability of nanoplasmas experimentally, in accordance with hydrodynamic nanoplasma models. In particular, the delay between the prepulse and the main pulse for maximum Rayleigh scattering is found to be longer than that for maximum x-ray emission, supporting the more refined one-dimensional self-consistent hydrodynamic nanoplasma model

Significant enhancement in volumetric and gravimetric capacitance of Cu-TiO2/PPY composite for supercapacitor application

Science.gov (United States)

Purty, B.; Choudhary, R. B.

2018-04-01

Copper doped titanium dioxide-polypyrrole (Cu-TiO2/PPY) composite was successfully synthesized via chemical oxidative in-situ polymerization process. The structural and morphological properties of Cu-TiO2/PPY composite were investigated using X-ray diffractometer (XRD), field emission electron microscopy (FESEM) and transmission electron microscopy(TEM) techniques. The electrochemical properties of as-synthesized composite were studied using cyclic voltammetry (CV), galvanostatic charge discharge (GCD) and electrochemical impedance spectroscopic (EIS) techniques. The novel Cu-TiO2/PPY composite showed enhanced volumetric capacitance ˜714 F cm-1 and gravimetric capacitance ˜674 F g-1 at 1 A g-1. In addition an excellent coulombic efficiency and comparabley low charge transfer resistance than pure PPY suggests improved supercapacitive performance of Cu-TiO2/PPY composite as an electrode material.

Nano-silver mediated polymerization of pyrrole: synthesis and gas sensing properties of polypyrrole (PPy)/Ag nano-composite.

Science.gov (United States)

Kate, Kunal H; Damkale, Shubhangi R; Khanna, P K; Jain, G H

2011-09-01

Thermal polymerization of pyrrole was performed using silver nitrate as source of silver ions followed by its conversion to Polypyrrole (PPy)/Ag nano-comoposites without using any external oxidizing agent or solvent. The formation of PPy was monitored by UV-Visible absorption spectroscopy showing a band at approximately 464 nm. XRD measurement confirmed characteristic peaks for face centered cubic (fcc) silver and presence of PPy at 2 theta of approximately 23 degrees suggesting the formation of PPy/Ag nanocomposite. Transmission electron microscopy (TEM) images showed non-aggregated spherical Ag nano-particles of about 5-10 nm. PPy/Ag thick film acts as a NH3 sensor at 100 degrees C, a H2S sensor at 250 degrees C and CO2 sensor at 350 degrees C. The thick films showed capability to recognize various gases at different operating temperature.

Ionic motion in PEDOT and PPy conducting polymer bilayers

DEFF Research Database (Denmark)

Zainudeen, Umer L.; Careem, M.A.; Skaarup, Steen

2006-01-01

Conducting polymer bilayers with poly(3,4-ethylenedioxythiophene) (PEDOT) and polypyrrole (PPy), each containing dodecyl benzenesulfonate (DBS) as immobile dopant species, were synthesized galvanostatically. The electrochemical behaviour of the bilayers was investigated using cyclic voltammetry...

BDNF Val66Met Genotype Interacts With a History of Simulated Stress Exposure to Regulate Sensorimotor Gating and Startle Reactivity.

Science.gov (United States)

Notaras, Michael J; Hill, Rachel A; Gogos, Joseph A; van den Buuse, Maarten

2017-05-01

Reduced expression of Brain-Derived Neurotrophic Factor (BDNF) has been implicated in the pathophysiology of schizophrenia. The BDNF Val66Met polymorphism, which results in deficient activity-dependent secretion of BDNF, is associated with clinical features of schizophrenia. We investigated the effect of this polymorphism on Prepulse Inhibition (PPI), a translational model of sensorimotor gating which is disrupted in schizophrenia. We utilized humanized BDNFVal66Met (hBDNFVal66Met) mice which have been modified to carry the Val66Met polymorphism, as well as express humanized BDNF in vivo. We also studied the long-term effect of chronic corticosterone (CORT) exposure in these animals as a model of history of stress. PPI was assessed at 30ms and 100ms interstimulus intervals (ISI). Analysis of PPI at the commonly used 100ms ISI identified that, irrespective of CORT treatment, the hBDNFVal/Met genotype was associated with significantly reduced PPI. In contrast, PPI was not different between hBDNFMet/Met and hBDNFVal/Val genotype mice. At the 30ms ISI, CORT treatment selectively disrupted sensorimotor gating of hBDNFVal/Met heterozygote mice but not hBDNFVal/Val or hBDNFMet/Met mice. Analysis of startle reactivity revealed that chronic CORT reduced startle reactivity of hBDNFVal/Val male mice by 51%. However, this was independent of the effect of CORT on PPI. In summary, we provide evidence of a distinct BDNFVal66Met heterozygote-specific phenotype using the sensorimotor gating endophenotype of schizophrenia. These data have important implications for clinical studies where, if possible, the BDNFVal/Met heterozygote genotype should be distinguished from the BDNFMet/Met genotype. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Performance of the Chemical and Electrochemical Composites of PPy/CNT as Electrodes in Type I Supercapacitors

Directory of Open Access Journals (Sweden)

S. C. Canobre

2015-01-01

Full Text Available Polypyrrole (PPy is one of the most studied conducting polymers and a very promising material for various applications such as lithium-ion secondary batteries, light-emitting devices, capacitors, and supercapacitors, owing to its many advantages, including good processability, easy handling, and high electronic conductivity. In this work, PPy films were chemically and electrochemically synthesized, both in and around carbon nanotubes (CNTs. The cyclic voltammograms of the device, composed of the electrochemically synthesized PPy/CNT composites as working and counter electrodes (Type I supercapacitor with p-type doping, showed a predominantly capacitive profile with low impedance values and good electrochemical stability, with the anodic charge remaining almost constant (11.38 mC, a specific capacitance value of 530 F g−1 after 50 charge and discharge cycles, and a coulombic efficiency of 99.2%. The electrochemically synthesized PPy/CNT composite exhibited better electrochemical properties compared to those obtained for the chemically synthesized composite. Thus, the electrochemically synthesized PPy/CNT composite is a promising material to be used as electrodes in Type I supercapacitors.

Prenatal immune challenge in rats: altered responses to dopaminergic and glutamatergic agents, prepulse inhibition of acoustic startle, and reduced route-based learning as a function of maternal body weight gain after prenatal exposure to poly IC.

Science.gov (United States)

Vorhees, Charles V; Graham, Devon L; Braun, Amanda A; Schaefer, Tori L; Skelton, Matthew R; Richtand, Neil M; Williams, Michael T

2012-08-01

Prenatal maternal immune activation has been used to test the neurodevelopmental hypothesis of schizophrenia. Most of the data are in mouse models; far less is available for rats. We previously showed that maternal weight change in response to the immune activator polyinosinic-polycytidylic acid (Poly IC) in rats differentially affects offspring. Therefore, we treated gravid Harlan Sprague-Dawley rats i.p. on embryonic day 14 with 8 mg/kg of Poly IC or Saline. The Poly IC group was divided into those that lost or gained the least weight, Poly IC (L), versus those that gained the most weight, Poly IC (H), following treatment. The study design controlled for litter size, litter sampling, sex distribution, and test experience. We found no effects of Poly IC on elevated zero maze, open-field activity, object burying, light-dark test, straight channel swimming, Morris water maze spatial acquisition, reversal, or shift navigation or spatial working or reference memory, or conditioned contextual or cued fear or latent inhibition. The Poly IC (H) group showed a significant decrease in the rate of route-based learning when visible cues were unavailable in the Cincinnati water maze and reduced prepulse inhibition of acoustic startle in females, but not males. The Poly IC (L) group exhibited altered responses to acute pharmacological challenges: exaggerated hyperactivity in response to (+)-amphetamine and an attenuated hyperactivity in response to MK-801. This model did not exhibit the cognitive, or latent inhibition deficits reported in Poly IC-treated rats but showed changes in response to drugs acting on neurotransmitter systems implicated in the pathophysiology of schizophrenia (dopaminergic hyperfunction and glutamatergic hypofunction). Copyright © 2012 Wiley Periodicals, Inc.

Pedot and PPy Conducting Polymer Bilayer and Trilayer Actuators

DEFF Research Database (Denmark)

Zainudeen, Umer Lebbe; Careem, Mohamed Abdul; Skaarup, Steen

2008-01-01

attempts have been made to improve the actuator performance. We report electromechanical measurements on actuators of bilayer and trilayer free standing films prepared with polypyrrole (PPy) and poly(3,4-ethylenedioxythiophene) (PEDOT) conducting polymers. Both types of conducting polymer are pre...

Frequency of reporting on patient and public involvement (PPI) in research studies published in a general medical journal: a descriptive study.

Science.gov (United States)

Price, Amy; Schroter, Sara; Snow, Rosamund; Hicks, Melissa; Harmston, Rebecca; Staniszewska, Sophie; Parker, Sam; Richards, Tessa

2018-03-23

While documented plans for patient and public involvement (PPI) in research are required in many grant applications, little is known about how frequently PPI occurs in practice. Low levels of reported PPI may mask actual activity due to limited PPI reporting requirements. This research analysed the frequency and types of reported PPI in the presence and absence of a journal requirement to include this information. A before and after comparison of PPI reported in research papers published in The BMJ before and 1 year after the introduction of a journal policy requiring authors to report if and how they involved patients and the public within their papers. Between 1 June 2013 and 31 May 2014, The BMJ published 189 research papers and 1 (0.5%) reported PPI activity. From 1 June 2015 to 31 May 2016, following the introduction of the policy, The BMJ published 152 research papers of which 16 (11%) reported PPI activity. Patients contributed to grant applications in addition to designing studies through to coauthorship and participation in study dissemination. Patient contributors were often not fully acknowledged; 6 of 17 (35%) papers acknowledged their contributions and 2 (12%) included them as coauthors. Infrequent reporting of PPI activity does not appear to be purely due to a failure of documentation. Reporting of PPI activity increased after the introduction of The BMJ 's policy, but activity both before and after was low and reporting was inconsistent in quality. Journals, funders and research institutions should collaborate to move us from the current situation where PPI is an optional extra to one where PPI is fully embedded in practice throughout the research process. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Packaged Au-PPy valves for drug delivery systems

Science.gov (United States)

Tsai, Han-Kuan A.; Ma, Kuo-Sheng; Zoval, Jim; Kulinsky, Lawrence; Madou, Marc

2006-03-01

The most common methods for the drug delivery are swallowing pills or receiving injections. However, formulations that control the rate and period of medicine (i.e., time-release medications) are still problematic. The proposed implantable devices which include batteries, sensors, telemetry, valves, and drug storage reservoirs provide an alternative method for the responsive drug delivery system [1]. Using this device, drug concentration can be precisely controlled which enhances drug efficiency and decreases the side effects. In order to achieve responsive drug delivery, a reliable release valve has to be developed. Biocompatibility, low energy consumption, and minimized leakage are the main requirements for such release method. A bilayer structure composed of Au/PPy film is fabricated as a flap to control the release valve. Optimized potentiostatic control to synthesize polypyrrole (PPy) is presented. The release of miniaturize valve is tested and showed in this paper. A novel idea to simultaneously fabricate the device reservoirs as well as protective packaging is proposed in this paper. The solution of PDMS permeability problem is also mentioned in this article.

A single high dose of escitalopram disrupts sensory gating and habituation, but not sensorimotor gating in healthy volunteers

DEFF Research Database (Denmark)

Oranje, Bob; Wienberg, Malene; Glenthøj, Birte Yding

2011-01-01

Early mechanisms to limit the input of sensory information to higher brain areas are important for a healthy individual. In previous studies, we found that a low dose of 10mg escitalopram (SSRI) disrupts habituation, without affecting sensory and sensorimotor gating in healthy volunteers. In the ......Early mechanisms to limit the input of sensory information to higher brain areas are important for a healthy individual. In previous studies, we found that a low dose of 10mg escitalopram (SSRI) disrupts habituation, without affecting sensory and sensorimotor gating in healthy volunteers....... In the current study a higher dose of 15mg was used. The hypothesis was that this higher dose of escitalopram would not only disrupt habituation, but also sensory and sensorimotor gating. Twenty healthy male volunteers received either placebo or 15mg escitalopram, after which they were tested in a P50...... suppression, and a habituation and prepulse inhibition (PPI) of the startle reflex paradigm. Escitalopram significantly decreased P50 suppression and habituation, but had no effect on PPI. The results indicate that habituation and sensory gating are disrupted by increased serotonergic activity, while...

A validity assessment of the Progress out of Poverty Index (PPI)™.

Science.gov (United States)

Desiere, Sam; Vellema, Wytse; D'Haese, Marijke

2015-04-01

Development organisations need easy-to-use and quick-to-implement indicators to quantify poverty when requested to measure program impact. In this paper we assess the validity of the Progress out of Poverty Index (PPI)™, a country-specific indicator based on ten closed questions on directly observable household characteristics, by its compliance to the SMART criteria. Each response receives a pre-determined score, such that the sum of these scores can be converted into the likelihood the household is living below the poverty line. We focus on the PPI scorecard for Rwanda, which was validated using two national household surveys conducted in 2005/06 and 2010/11. The PPI is Specific, Measurable, Available cost effectively, and Timely available. Yet, its Relevance depends on the way it is used. Although it accurately distinguishes poor from non-poor households, making it a useful reporting tool, its limited sensitivity to changes in poverty status restricts its usefulness for evaluating the impact of development projects. Copyright © 2014 Elsevier Ltd. All rights reserved.

Identifying protein complex by integrating characteristic of core-attachment into dynamic PPI network.

Directory of Open Access Journals (Sweden)

Xianjun Shen

Full Text Available How to identify protein complex is an important and challenging task in proteomics. It would make great contribution to our knowledge of molecular mechanism in cell life activities. However, the inherent organization and dynamic characteristic of cell system have rarely been incorporated into the existing algorithms for detecting protein complexes because of the limitation of protein-protein interaction (PPI data produced by high throughput techniques. The availability of time course gene expression profile enables us to uncover the dynamics of molecular networks and improve the detection of protein complexes. In order to achieve this goal, this paper proposes a novel algorithm DCA (Dynamic Core-Attachment. It detects protein-complex core comprising of continually expressed and highly connected proteins in dynamic PPI network, and then the protein complex is formed by including the attachments with high adhesion into the core. The integration of core-attachment feature into the dynamic PPI network is responsible for the superiority of our algorithm. DCA has been applied on two different yeast dynamic PPI networks and the experimental results show that it performs significantly better than the state-of-the-art techniques in terms of prediction accuracy, hF-measure and statistical significance in biology. In addition, the identified complexes with strong biological significance provide potential candidate complexes for biologists to validate.

Oesophageal narrowing on barium oesophagram is more common in adult patients with eosinophilic oesophagitis than PPI-responsive oesophageal eosinophilia.

Science.gov (United States)

Podboy, A; Katzka, D A; Enders, F; Larson, J J; Geno, D; Kryzer, L; Alexander, J

2016-06-01

To date there have been no clear features that aid in differentiating patients with eosinophilic oesophagitis (EoE) from PPI-responsive oesophageal eosinophilia (PPI-REE). However, barium swallow roentgenography is a more sensitive and specific measure to detect subtle fibrostenotic remodeling changes present in EoE. We aim to characterise any clinical, endoscopic, histiological or barium roentgenographic differences between EoE and PPI-REE. To characterise any clinical, endoscopic, histiological or barium roentgenographic differences between EoE and PPI-REE. We performed a retrospective cohort analysis on data collected from a tertiary referral centre population from 2010 to 2015. Data from 66 patients with EoE and 28 patients with PPI-REE were analysed. Cases were adults who met consensus guidelines for EOE, and had a barium swallow study within 6 months of the index endoscopy. Clinical, endoscopic, histiological and barium swallow findings were collected. Patients with EoE reported similar characteristics as PPI-REE patients, except EoE patients were younger (35.6 vs. 46.6 years; P = 0.011), had earlier symptom onset (29.0 vs. 38.0 years; P = 0.026), and smaller oesophageal diameters on barium swallow (19.5 mm vs. 20; P = 0.042). Patients with EoE were more likely to have distal strictures (EoE 77% vs. 25%; P = 0.02) and, importantly, a greater likelihood of small calibre oesophagus (51.5% vs. 17.9%; P = 0.002). Moreover, EoE patients had a higher probability of developing small calibre oesophagus after 20 years of symptoms (72.3% vs. 30.2%; P = 0.074) compared to PPI-REE patients. When compared with eosinophilic oesophagitis, PPI-REE patients demonstrate findings that suggest PPI-responsive oesophageal eosinophilia to be a later onset, less aggressive form of oesophageal stricturing disease than eosinophilic oesophagitis. © 2016 John Wiley & Sons Ltd.

Evolutionary, kinetic and thermodynamic aspects on the bioenergetics of inorganic pyrophosphate (PPi) and adenosine triphosphate (ATP)

International Nuclear Information System (INIS)

Baltscheffsky, H.; Baltscheffsky, M.

1995-01-01

Energy barriers for energy carriers are of fundamental significance for the successful operation of the bioenergetic reactions in living cells. PPi and ATP are outstanding ''energy-rich'' examples of molecular ''energy currencies'' in biological systems, with kinetic barriers preventing excessively fast thermodynamically feasible hydrolysis from occurring. The barriers may be considered to facilitate the energy coupling roles of these phosphate compounds, which are to secure growth and maintain numerous other energy requiring functions. The enzymes involved in overcoming the energies of activation of the bioenergetic reactions have evolved to be very well tuned for their roles. Three aspects will be discussed in some detail. The first is the fact that ATP at neutral pH is considerably more energy-rich than PPi, which thus has been called a ''poor man's ATP''. This is exemplified by the kinetic and thermodynamic differences observed between the requirements for the photosynthetic formation of PPi and ATP in certain photobacterial chromatophores by varying levels of energy supply. At lower pH, PPi and ATP are equally energy-rich, which may be of significance for acidophiles. The second concerns the possible evolutionary significance of the finding that, in the dark, a pH gradient suffices to drive extensive PPi synthesis, whereas ATP synthesis requires both a pH gradient and a membrane potential (Strid et al, Biochim. Biophys. Acta 892 (1987) 236-244). Thirdly, PPi as the most plausible predecessor to ATP in the origin and early evolution of life, will be discussed. (author). Abstract only

Prepulse and amplified spontaneous emission effects on the interaction of a petawatt class laser with thin solid targets

Energy Technology Data Exchange (ETDEWEB)

Esirkepov, Timur Zh. [QuBS, Japan Atomic Energy Agency, Kizugawa, Kyoto 619-0215 (Japan); Koga, James K., E-mail: koga.james@jaea.go.jp [QuBS, Japan Atomic Energy Agency, Kizugawa, Kyoto 619-0215 (Japan); Sunahara, Atsushi [Institute for Laser Technology, 2-6 Yamadaoka Suita, Osaka 565-0871 (Japan); Morita, Toshimasa; Nishikino, Masaharu [QuBS, Japan Atomic Energy Agency, Kizugawa, Kyoto 619-0215 (Japan); Kageyama, Kei [Graduate School of Engineering, Osaka University, Osaka 565-0871 (Japan); Nagatomo, Hideo; Nishihara, Katsunobu [Institute of Laser Engineering, 2-6 Yamadaoka Suita, Osaka 565-0871 (Japan); Sagisaka, Akito; Kotaki, Hideyuki; Nakamura, Tatsufumi; Fukuda, Yuji; Okada, Hajime; Pirozhkov, Alexander S.; Yogo, Akifumi; Nishiuchi, Mamiko; Kiriyama, Hiromitsu; Kondo, Kiminori; Kando, Masaki [QuBS, Japan Atomic Energy Agency, Kizugawa, Kyoto 619-0215 (Japan); Bulanov, Sergei V. [QuBS, Japan Atomic Energy Agency, Kizugawa, Kyoto 619-0215 (Japan); A.M. Prokhorov Institute of General Physics of RAS, Vavilova st. 38, Moscow 117942 (Russian Federation); Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region 141700 (Russian Federation)

2014-05-01

When a finite contrast petawatt laser pulse irradiates a micron-thick foil, a prepulse (including amplified spontaneous emission) creates a preplasma, where an ultrashort relativistically strong portion of the laser pulse (the main pulse) acquires higher intensity due to relativistic self-focusing and undergoes fast depletion transferring energy to fast electrons. If the preplasma thickness is optimal, the main pulse can reach the target accelerating fast ions more efficiently than an ideal, infinite contrast, laser pulse. A simple analytical model of a target with preplasma formation is developed and the radiation pressure dominant acceleration of ions in this target is predicted. The preplasma formation by a nanosecond prepulse is analyzed with dissipative hydrodynamic simulations. The main pulse interaction with the preplasma is studied with multi-parametric particle-in-cell simulations. The optimal conditions for hundreds of MeV ion acceleration are found with accompanying effects important for diagnostics, including high-order harmonics generation.

Tautomeric forms of PPI dendrimers functionalized with 4-(4′-ethoxybenzoyloxy)salicylaldehyde chromophores

International Nuclear Information System (INIS)

Franckevičius, M.; Vaišnoras, R.; Marcos, M.; Serrano, J.L.; Gruodis, A.; Galikova, N.; Gulbinas, V.

2012-01-01

Highlights: ► SA chromophore groups are formed by bonding terminal groups to PPI dendrimers. ► SA chromophore groups reveal four most stable tautomeric forms. ► Tautomeric properties of SA groups depend on the dendrimer generation and solvent. ► Aggregation of SA chromophores facilitates formation of the trans-keto tautomers. ► Fluorescence of PPI SA dendrimers is attributed to nπ ∗ states of keto tautomers. -- Abstract: Bonding of the promesogenic unit derived from 4-(4′-ethoxybenzoyloxy)salicylaldehyde to the amino terminated PPI dendrimer chains results in formation of the salicylidenimine chromophore groups. Absorption and fluorescence investigations of the dendrimer solutions supported by the quantum chemistry calculations revealed that the chromophore groups may exist in enol and keto tautomeric forms with relative concentrations depending on the dendrimer generation and solvent. The dendrimer fluorescence is attributed to nπ ∗ states of keto tautomers which may also be formed from excited enol tautomers.

Preparation of stable magnetic nanofluids containing Fe3O4@PPy nanoparticles by a novel one-pot route

Directory of Open Access Journals (Sweden)

Zhao Baobao

2011-01-01

Full Text Available Abstract Stable magnetic nanofluids containing Fe3O4@Polypyrrole (PPy nanoparticles (NPs were prepared by using a facile and novel method, in which one-pot route was used. FeCl3·6H2O was applied as the iron source, and the oxidizing agent to produce PPy. Trisodium citrate (Na3cit was used as the reducing reagent to form Fe3O4 NPs. The as-prepared nanofluid can keep long-term stability. The Fe3O4@PPy NPs can still keep dispersing well after the nanofluid has been standing for 1 month and no sedimentation is found. The polymerization reaction of the pyrrole monomers took place with Fe3+ ions as the initiator, in which these Fe3+ ions remained in the solution adsorbed on the surface of the Fe3O4 NPs. Thus, the core-shell NPs of Fe3O4@PPy were obtained. The particle size of the as-prepared Fe3O4@PPy can be easily controlled from 7 to 30 nm by the polymerization reaction of the pyrrole monomers. The steric stabilization and weight of the NPs affect the stability of the nanofluids. The as-prepared Fe3O4@PPy NPs exhibit superparamagnetic behavior.

PPI-IRO: A two-stage method for protein-protein interaction extraction based on interaction relation ontology

KAUST Repository

Li, Chuanxi

2014-01-01

Mining Protein-Protein Interactions (PPIs) from the fast-growing biomedical literature resources has been proven as an effective approach for the identifi cation of biological regulatory networks. This paper presents a novel method based on the idea of Interaction Relation Ontology (IRO), which specifi es and organises words of various proteins interaction relationships. Our method is a two-stage PPI extraction method. At fi rst, IRO is applied in a binary classifi er to determine whether sentences contain a relation or not. Then, IRO is taken to guide PPI extraction by building sentence dependency parse tree. Comprehensive and quantitative evaluations and detailed analyses are used to demonstrate the signifi cant performance of IRO on relation sentences classifi cation and PPI extraction. Our PPI extraction method yielded a recall of around 80% and 90% and an F1 of around 54% and 66% on corpora of AIMed and Bioinfer, respectively, which are superior to most existing extraction methods. Copyright © 2014 Inderscience Enterprises Ltd.

Status On Multi-microsecond Prepulse Technique On Sphinx Machine Going From Nested To Single Wire Array For 800 ns Implosion Time Z-pinch

Science.gov (United States)

Maury, P.; Calamy, H.; Grunenwald, J.; Lassalle, F.; Zucchini, F.; Loyen, A.; Georges, A.; Morell, A.; Bedoch, J. P.

2009-01-01

The Sphinx machine[1] is a 6 MA, 1 μS driver based on the LTD technology, used for Z-pinch experiments. Important improvements of Sphinx radiation output were recently obtained using a multi-microsecond current prepulse[2]. Total power per unit of length is multiplied by a factor of 6 and FWHM divided by a factor of 2.5. Early breakdown of the wires during the prepulse phase dramatically changes the ablation phase leading to an improvement of axial homogeneity of both the implosion and the final radiating column. As a consequence, the cathode bubble observed on classical shots is definitively removed. The implosion is then centered and zippering effect is reduced, leading to simultaneous x-ray emission of the whole length. A great reproducibility is obtained. Nested arrays were used before to mitigate the Rayleigh-Taylor instabilities during the implosion phase. Further experiments with pre-pulse technique are described here were inner array was removed. The goal of these experiments was to see if long prepulse could give stable enough implosion with single array and at the same time increase the η parameter by reducing the mass of the load. Experimental results of single wire array loads of typical dimension 5 cm in height with implosion time between 700 and 900 ns and diameter varying between 80 and 140 mm are given. Parameters of the loads were varying in term of radius and number of wires. Comparisons with nested wire array loads are done and trends are proposed. Characteristics of both the implosion and the final radiating column are shown. 2D MHD numerical simulations of single wire array become easier as there is no interaction between outer and inner array anymore. A systematic study was done using injection mass model to benchmark simulation with experiments.

Status On Multi-microsecond Prepulse Technique On Sphinx Machine Going From Nested To Single Wire Array For 800 ns Implosion Time Z-pinch

International Nuclear Information System (INIS)

Maury, P.; Calamy, H.; Grunenwald, J.; Lassalle, F.; Zucchini, F.; Loyen, A.; Georges, A.; Morell, A.; Bedoch, J. P.

2009-01-01

The Sphinx machine [1] is a 6 MA, 1 μS driver based on the LTD technology, used for Z-pinch experiments. Important improvements of Sphinx radiation output were recently obtained using a multi-microsecond current prepulse [2] . Total power per unit of length is multiplied by a factor of 6 and FWHM divided by a factor of 2.5. Early breakdown of the wires during the prepulse phase dramatically changes the ablation phase leading to an improvement of axial homogeneity of both the implosion and the final radiating column. As a consequence, the cathode bubble observed on classical shots is definitively removed. The implosion is then centered and zippering effect is reduced, leading to simultaneous x-ray emission of the whole length. A great reproducibility is obtained. Nested arrays were used before to mitigate the Rayleigh-Taylor instabilities during the implosion phase. Further experiments with pre-pulse technique are described here were inner array was removed. The goal of these experiments was to see if long prepulse could give stable enough implosion with single array and at the same time increase the η parameter by reducing the mass of the load. Experimental results of single wire array loads of typical dimension 5 cm in height with implosion time between 700 and 900 ns and diameter varying between 80 and 140 mm are given. Parameters of the loads were varying in term of radius and number of wires. Comparisons with nested wire array loads are done and trends are proposed. Characteristics of both the implosion and the final radiating column are shown. 2D MHD numerical simulations of single wire array become easier as there is no interaction between outer and inner array anymore. A systematic study was done using injection mass model to benchmark simulation with experiments.

Synthesis and characterization of a novel tube-in-tube nanostructured PPy/MnO2/CNTs composite for supercapacitor

International Nuclear Information System (INIS)

Li, Juan; Que, Tingli; Huang, Jianbin

2013-01-01

Graphical abstract: A novel tube-in-tube nanostructured PPy/MnO 2 /CNTs composite have been successfully fabricated. Its inner tubules are CNTs and the outer tubules are template-synthesized PPy. Most MnO 2 nanoparticles are sandwiched between the inner and outer wall, some relatively large particles are also latched onto the outside wall of the PPy tube. The composite yields a good electrochemical reversibility through 1000 cycles’ cyclic voltammogram (CV) test and galvanostatic charge–discharge experiments at different current densities. Display Omitted Highlights: ► We fabricate a ternary organic–inorganic complex of PPy/MnO 2 /CNTs composite. ► We characterize its morphological structures and properties by several techniques. ► The composite possesses the typical tube-in-tube nanostructures. ► Most MnO 2 nanoparticles are sandwiched between the inner CNTs and outer PPy wall. ► The composite has good electrochemical reversibility for supercapacitor. -- Abstract: Ternary organic–inorganic complex of polypyrrole/manganese dioxide/carbon nanotubes (PPy/MnO 2 /CNTs) composite was prepared by in situ chemical oxidation polymerization of pyrrole in the host of inorganic matrix of MnO 2 and CNTs, using complex of methyl orange (MO)/FeCl 3 was used as a reactive self-degraded soft-template. The morphological structures of the composite were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopic (HRTEM), Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD), respectively. All the results indicate that the PPy/MnO 2 /CNTs composite possesses the typical tube-in-tube nanostructures: the inner tubules are CNTs and the outer tubules are template-synthesized PPy. MnO 2 nanoparticles may either sandwich the space between the inner and outer tubules or directly latch onto the wall of the PPy tubes. The composite yields a good electrochemical

Electrochemomechanical Behaviour of Bilayer and Trilayer Films with PEDOT and PPY Conducting Polymers

DEFF Research Database (Denmark)

Zainudeen, Umer L.; Careem, M.A.; Skaarup, Steen

2008-01-01

a constant load of 1.5 g. The cyclic voltammograms as well as the UV-visible spectra of PEDOT and PPy are very different, pointing towards the possibility of being able to separate the two layers experimentally – even when combined in a single film. Bilayer results show combined characteristics of each...... layer is very thin compared to that of the PPy layer, and characterized using cyclic voltammetry, optical absorption spectroscopy and electrochemical quartz crystal microbalance (EQCM) techniques. Actuators of bilayer and trilayer free standing films were characterized electromechanically under...

Negative Effect of Proton-pump Inhibitors (PPIs) on Helicobacter pylori Growth, Morphology, and Urease Test and Recovery after PPI Removal--An In vitro Study.

Science.gov (United States)

Saniee, Parastoo; Shahreza, Somayeh; Siavoshi, Farideh

2016-04-01

Proton-pump inhibitor (PPI) consumption does lead to false-negative results of Helicobacter pylori diagnostic tests such as biopsy culture and rapid urease test (RUT). Helicobacter pylori isolates from 112 dyspeptic patients with (56.5%) or without (43.5%) PPI consumption were recruited for examining the negative effects of omeprazole (OMP), lansoprazole (LPZ), and pantoprazole (PAN) on H. pylori viability, morphology, and urease, in vitro. The effect of a sublethal concentration of OMP on bacterial features and their recovery after removal of OMP was also assessed. Of 112 culture-positive gastric biopsies, 87.5% were RUT positive and 12.5% RUT negative. There was a significant correlation between negative RUT results and PPI consumption (p urease of 90.3% of isolates between 0 and 40 minutes and 54.4% between 20 and 40 minutes, respectively. PAN did not inhibit H. pylori growth and urease. Three 3-day (9 days) consecutive subcultures of H. pylori on brucella blood agar (BBA) supplemented with OMP resulted in reduced bacterial viability (1+), compared with control (4+), change of spiral morphology to coccoid, and reduction in pink color intensity in urea agar. Bacterial growth (1+), morphology, and urease test did not improve after the first 3-day and second 3-day (6 days) subcultures on BBA. However, relative recovery occurred after the third 3-day (9 days) subculture and complete recovery was observed after the fourth 3-day (12 days) subculture, as confluent growth (4+), 100% spiral cells, and strong urease test. Proton-pump Inhibitors exert transient negative effects on H. pylori viability, morphology, and urease test. Accordingly, cessation of PPI consumption at least 12 days before endoscopy could help avoiding false-negative results of H. pylori diagnostic tests. © 2015 John Wiley & Sons Ltd.

Prepulse dependence in hard x-ray generation from microdroplets

International Nuclear Information System (INIS)

Anand, M.; Kahaly, S.; Kumar, G. Ravindra; Sandhu, A. S.; Gibbon, P.; Krishnamurthy, M.

2006-01-01

We report on experiments which show that liquid microdroplets are very efficient in hard x-ray generation. We make a comparative study of hard x-ray emission from 15 μm methanol microdroplets and a plain slab target of similar atomic composition at similar laser intensities. The hard X-ray yield from droplet plasmas is about 35 times more than that obtained from solid plasmas. A prepulse that is about 10ns and at least 2% in intensity of the main pulse is essential for hard x-ray generation from the droplets at about 1015 W cm-2. A hot electron temperature of 36 keV is measured from the droplets at 8 x 1014 W cm-2; three times higher intensity is needed to obtain similar hot electron temperature from solid plasmas that have similar atomic composition. We use 1D-PIC simulation to obtain qualitative correlation to the experimental observations

Synthesis and characterization of a novel tube-in-tube nanostructured PPy/MnO{sub 2}/CNTs composite for supercapacitor

Energy Technology Data Exchange (ETDEWEB)

Li, Juan, E-mail: lj-panpan@163.com [College of Chemistry and Chemical Engineering, Xinjiang University, Urumqi 830046 (China); Beijing National Laboratory for Molecular Sciences (BNLMS), State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871 (China); Que, Tingli [College of Chemistry and Chemical Engineering, Xinjiang University, Urumqi 830046 (China); Huang, Jianbin, E-mail: JBhuang@pku.edu.cn [College of Chemistry and Chemical Engineering, Xinjiang University, Urumqi 830046 (China); Beijing National Laboratory for Molecular Sciences (BNLMS), State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871 (China)

2013-02-15

Graphical abstract: A novel tube-in-tube nanostructured PPy/MnO{sub 2}/CNTs composite have been successfully fabricated. Its inner tubules are CNTs and the outer tubules are template-synthesized PPy. Most MnO{sub 2} nanoparticles are sandwiched between the inner and outer wall, some relatively large particles are also latched onto the outside wall of the PPy tube. The composite yields a good electrochemical reversibility through 1000 cycles’ cyclic voltammogram (CV) test and galvanostatic charge–discharge experiments at different current densities. Display Omitted Highlights: ► We fabricate a ternary organic–inorganic complex of PPy/MnO{sub 2}/CNTs composite. ► We characterize its morphological structures and properties by several techniques. ► The composite possesses the typical tube-in-tube nanostructures. ► Most MnO{sub 2} nanoparticles are sandwiched between the inner CNTs and outer PPy wall. ► The composite has good electrochemical reversibility for supercapacitor. -- Abstract: Ternary organic–inorganic complex of polypyrrole/manganese dioxide/carbon nanotubes (PPy/MnO{sub 2}/CNTs) composite was prepared by in situ chemical oxidation polymerization of pyrrole in the host of inorganic matrix of MnO{sub 2} and CNTs, using complex of methyl orange (MO)/FeCl{sub 3} was used as a reactive self-degraded soft-template. The morphological structures of the composite were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopic (HRTEM), Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD), respectively. All the results indicate that the PPy/MnO{sub 2}/CNTs composite possesses the typical tube-in-tube nanostructures: the inner tubules are CNTs and the outer tubules are template-synthesized PPy. MnO{sub 2} nanoparticles may either sandwich the space between the inner and outer tubules or directly latch onto the wall of the PPy tubes. The composite

Three-dimensional (3D α-Fe2O3/polypyrrole (PPy nanocomposite for effective electromagnetic absorption

Directory of Open Access Journals (Sweden)

Wanchun Jiang

2016-06-01

Full Text Available The lightweight and 3-dimensional reticulated α-Fe2O3/PPy hybrids were successfully fabricated via a facile one-pot polyreaction. The measured complex permittivity and microwave attenuation performance suggest that the dielectric properties of PPy can be regulated by the mass ratio of added α-Fe2O3. The two dielectric resonance peaks of complex permittivity can be ascribed to the interface capacitor-like structure. An equivalent circuit model was established to explain the nonlinear resonance behavior of the α-Fe2O3/PPy wax composites. The addition of α-Fe2O3 properly tuned the dielectric constant to endow the composites with highly efficient microwave absorption. The minimum reflection loss of α-Fe2O3/PPy wax composites were enhanced to nearly −29dB with an effective bandwidth (RL≤ − 10dB up to 5.0GHz. The numerical method was proposed to calculate the optimum thickness for minimum RL at expected frequency by detailed investigation on the transmission formula. Moreover, the required thickness for optimum absorption efficiency at expected frequency can be obtained directly.

Reflux parameters as modified by laparoscopic fundoplication in 40 patients with heartburn/regurgitation persisting despite PPI therapy: a study using impedance-pH monitoring.

Science.gov (United States)

Frazzoni, Marzio; Conigliaro, Rita; Melotti, Gianluigi

2011-04-01

Patients with typical reflux symptoms (heartburn/regurgitation) persisting despite proton pump inhibitor (PPI) therapy are not uncommon. Impedance-pH monitoring detects gastroesophageal reflux at all pH levels and may establish if ongoing symptoms on PPI therapy are associated with acid/nonacid reflux. Laparoscopic fundoplication is a therapeutic option in such patients but reflux parameters on PPI therapy and after intervention and their relationship with symptom persistence/remission have been scarcely studied. The aim of this study was to assess reflux parameters and their relationship with symptoms before and after laparoscopic fundoplication, on and off PPI therapy, respectively, in patients with PPI-unresponsive heartburn/regurgitation and with a positive symptom-reflux association and/or abnormal reflux parameters detected on PPI therapy. Impedance-pH monitoring was performed on high-dose PPI therapy and 3 months after laparoscopic fundoplication, off PPI therapy, in 40 patients with PPI-unresponsive heartburn/regurgitation. Symptoms were scored by a validated questionnaire. Esophageal acid exposure time as well as the number of total and proximal reflux events and of acid and weakly acidic refluxes decreased significantly after surgery: normal values were found in 100, 77, 95, 92 and 65% of cases, respectively. Weakly alkaline refluxes increased significantly postoperatively but neither before nor after intervention were associated with symptoms. All patients reported total/subtotal remission of heartburn/regurgitation 3 months after surgery. Laparoscopic fundoplication improves acid and weakly acidic reflux parameters when compared with PPI therapy. This improvement justifies the very high post-surgical symptom remission rate that we observed. Prolonged follow-up is warranted but our findings strongly support the surgical option in PPI failures.

Selective Phosphonylation of 5'-Adenosine Monophosphate (5'-AMP) via Pyrophosphite [PPi(III)].

Science.gov (United States)

Kaye, Karl; Bryant, David E; Marriott, Katie E R; Ohara, Shohei; Fishwick, Colin W G; Kee, Terence P

2016-11-01

We describe here experiments which demonstrate the selective phospho-transfer from a plausibly prebiotic condensed phosphorus (P) salt, pyrophosphite [H 2 P 2 O 5 2- ; PPi(III)], to the phosphate group of 5'-adenosine mono phosphate (5'-AMP). We show further that this P-transfer process is accelerated both by divalent metal ions (M 2+ ) and by organic co-factors such as acetate (AcO - ). In this specific case of P-transfer from PPi(III) to 5'-AMP, we show a synergistic enhancement of transfer in the combined presence of M 2+ & AcO - . Isotopic labelling studies demonstrate that hydrolysis of the phosphonylated 5'-AMP, [P(III)P(V)-5'-AMP], proceeds via nuceophilic attack of water at the Pi(III) terminus.

Preparation of PPy-Coated MnO2 Hybrid Micromaterials and Their Improved Cyclic Performance as Anode for Lithium-Ion Batteries.

Science.gov (United States)

Feng, Lili; Zhang, Yinyin; Wang, Rui; Zhang, Yanli; Bai, Wei; Ji, Siping; Xuan, Zhewen; Yang, Jianhua; Zheng, Ziguang; Guan, Hongjin

2017-09-02

MnO 2 @PPy core-shell micromaterials are prepared by chemical polymerization of pyrrole on the MnO 2 surface. The polypyrrole (PPy) is formed as a homogeneous organic shell on the MnO 2 surface. The thickness of PPy shell can be adjusted by the usage of pyrrole. The analysis of SEM, FT-IR, X-ray photoelectron spectroscopy (XPS), thermo-gravimetric analysis (TGA), and XRD are used to confirm the formation of PPy shell. Galvanostatic cell cycling and electrochemical impedance spectroscopy (EIS) are used to evaluate the electrochemical performance as anode for lithium-ion batteries. The results show that after formation of MnO 2 @PPy core-shell micromaterials, the cyclic performance as anode for lithium-ion batteries is improved. Fifty microliters of PPy-coated caddice-clew-like MnO 2 has the best cyclic performances as has 620 mAh g -1 discharge specific capacities after 300 cycles. As a comparison, the discharge specific capacity of bare MnO 2 materials falls to below 200 mAh g -1 after 10 cycles. The improved lithium-storage cyclic stability of the MnO 2 @PPy samples attributes to the core-shell hybrid structure which can buffer the structural expansion and contraction of MnO 2 caused by the repeated embedding and disengagement of Li ions and can prevent the pulverization of MnO 2 . This experiment provides an effective way to mitigate the problem of capacity fading of the transition metal oxide materials as anode materials for (lithium-ion batteries) LIBs.

The Arabidopsis ppi1 Mutant Is Specifically Defective in the Expression, Chloroplast Import, and Accumulation of Photosynthetic ProteinsW⃞

Science.gov (United States)

Kubis, Sybille; Baldwin, Amy; Patel, Ramesh; Razzaq, Azam; Dupree, Paul; Lilley, Kathryn; Kurth, Joachim; Leister, Dario; Jarvis, Paul

2003-01-01

The import of nucleus-encoded proteins into chloroplasts is mediated by translocon complexes in the envelope membranes. A component of the translocon in the outer envelope membrane, Toc34, is encoded in Arabidopsis by two homologous genes, atTOC33 and atTOC34. Whereas atTOC34 displays relatively uniform expression throughout development, atTOC33 is strongly upregulated in rapidly growing, photosynthetic tissues. To understand the reason for the existence of these two related genes, we characterized the atTOC33 knockout mutant ppi1. Immunoblotting and proteomics revealed that components of the photosynthetic apparatus are deficient in ppi1 chloroplasts and that nonphotosynthetic chloroplast proteins are unchanged or enriched slightly. Furthermore, DNA array analysis of 3292 transcripts revealed that photosynthetic genes are moderately, but specifically, downregulated in ppi1. Proteome differences in ppi1 could be correlated with protein import rates: ppi1 chloroplasts imported the ribulose-1,5-bisphosphate carboxylase/oxygenase small subunit and 33-kD oxygen-evolving complex precursors at significantly reduced rates, but the import of a 50S ribosomal subunit precursor was largely unaffected. The ppi1 import defect occurred at the level of preprotein binding, which is consistent with a role for atToc33 during preprotein recognition. The data suggest that atToc33 is involved preferentially in the import of photosynthetic proteins and, by extension, that atToc34 is involved in the import of nonphotosynthetic chloroplast proteins. PMID:12897258

kW-class picosecond thin-disc prepulse laser Perla for efficient EUV generation

Czech Academy of Sciences Publication Activity Database

Endo, Akira; Smrž, Martin; Mužík, Jiří; Novák, Ondřej; Chyla, Michal; Mocek, Tomáš

2017-01-01

Roč. 16, č. 4 (2017), s. 1-6, č. článku 041011. ISSN 1932-5150 R&D Projects: GA MŠk LO1602; GA ČR GA16-12960S; GA MŠk LM2015086 EU Projects: European Commission(XE) 739573 - HiLASE CoE Grant - others:OP VVV - HiLASE-CoE(XE) CZ.02.1.01/0.0/0.0/15_006/0000674 Institutional support: RVO:68378271 Keywords : EUV source * laser produced plasma * FEL * prepulse * thin-disc laser Subject RIV: BH - Optics, Masers, Laser s OBOR OECD: Optics (including laser optics and quantum optics) Impact factor: 1.350, year: 2016

Blast-Induced Tinnitus and Elevated Central Auditory and Limbic Activity in Rats: A Manganese-Enhanced MRI and Behavioral Study.

Science.gov (United States)

Ouyang, Jessica; Pace, Edward; Lepczyk, Laura; Kaufman, Michael; Zhang, Jessica; Perrine, Shane A; Zhang, Jinsheng

2017-07-07

Blast-induced tinitus is the number one service-connected disability that currently affects military personnel and veterans. To elucidate its underlying mechanisms, we subjected 13 Sprague Dawley adult rats to unilateral 14 psi blast exposure to induce tinnitus and measured auditory and limbic brain activity using manganese-enhanced MRI (MEMRI). Tinnitus was evaluated with a gap detection acoustic startle reflex paradigm, while hearing status was assessed with prepulse inhibition (PPI) and auditory brainstem responses (ABRs). Both anxiety and cognitive functioning were assessed using elevated plus maze and Morris water maze, respectively. Five weeks after blast exposure, 8 of the 13 blasted rats exhibited chronic tinnitus. While acoustic PPI remained intact and ABR thresholds recovered, the ABR wave P1-N1 amplitude reduction persisted in all blast-exposed rats. No differences in spatial cognition were observed, but blasted rats as a whole exhibited increased anxiety. MEMRI data revealed a bilateral increase in activity along the auditory pathway and in certain limbic regions of rats with tinnitus compared to age-matched controls. Taken together, our data suggest that while blast-induced tinnitus may play a role in auditory and limbic hyperactivity, the non-auditory effects of blast and potential traumatic brain injury may also exert an effect.

Involvement of posterior cingulate cortex in ketamine-induced psychosis relevant behaviors in rats.

Science.gov (United States)

Ma, Jingyi; Leung, L Stan

2018-02-15

The involvement of posterior cingulate cortex (PCC) on ketamine-induced psychosis relevant behaviors was investigated in rats. Bilateral infusion of muscimol, a GABA A receptor agonist, into the PCC significantly antagonized ketamine-induced deficit in prepulse inhibition of a startle reflex (PPI), deficit in gating of hippocampal auditory evoked potentials, and behavioral hyperlocomotion in a dose dependent manner. Local infusion of ketamine directly into the PCC also induced a PPI deficit. Systemic injection of ketamine (3mg/kg,s.c.) induced an increase in power of electrographic activity in the gamma band (30-100Hz) in both the PCC and the hippocampus; peak theta (4-10Hz) power was not significantly altered, but peak theta frequency was increased by ketamine. In order to exclude volume conduction from the hippocampus to PCC, inactivation of the hippocampus was made by local infusion of muscimol into the hippocampus prior to ketamine administration. Muscimol in the hippocampus effectively blocked ketamine-induced increase of gamma power in the hippocampus but not in the PCC, suggesting independent generation of gamma waves in PCC and hippocampus. It is suggested that the PCC is part of the brain network mediating ketamine-induced psychosis related behaviors. Copyright © 2017 Elsevier B.V. All rights reserved.

Modification of Screen Printed Carbon Electrode (SPCE with Polypyrrole (Ppy-SiO2 for Phenol Determination

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Ani Mulyasuryani

2018-01-01

Full Text Available Electrode modification on screen printed carbon electrode (SPCE with polypyrrole (Ppy-SiO2 was done by electropolymerization. Polypyrrole (Ppy-SiO2 was used for phenol determination. The analysis of this material was done by using Scanning Electron Microscopy (SEM, cyclic voltammetry method and differential pulse voltammetry. In a cyclic voltammetry analysis, we used potential range of -1 to 1 V with Ag/AgCl comparator electrode at scan rate of 100 mV/sec, while in differential pulse voltammetry method the potential range was 0 to 1 V toward Ag/AgCl, the scan rate of 50 mV/sec, the pulse rate is 0,2 V and the pulse width is 50 ms. From the analysis result with SEM, cyclic voltammetry and differential pulse voltammetry method, Polypyrrole (Ppy -SiO2 is the best material and can be used as phenol measurement.

Fabrication of conductive and high-dispersed Ppy@Ag/g-C{sub 3}N{sub 4} composite photocatalysts for removing various pollutants in water

Energy Technology Data Exchange (ETDEWEB)

Zhu, Zhi; Tang, Xu [School of Chemistry and Chemical Engineering, Jiangsu University (China); Ma, Changchang [School of the Environment and Safety Engineering, Jiangsu University (China); Song, Minshan [School of Mathematics and Physics, Jiangsu University of Science and Technology (China); Gao, Nailing; Wang, Youshan; Huo, Pengwei [School of Chemistry and Chemical Engineering, Jiangsu University (China); Lu, Ziyang, E-mail: mrzhuzhi007@163.com [School of the Environment and Safety Engineering, Jiangsu University (China); Yan, Yongsheng, E-mail: gchxz206@126.com [School of Chemistry and Chemical Engineering, Jiangsu University (China)

2016-11-30

Highlights: • The high-dispersed Ag modified g-C{sub 3}N{sub 4} (Ag/g-C{sub 3}N{sub 4}) was successfully synthesized in situ deposited on the surface of g-C{sub 3}N{sub 4} during calcined melamine. • The as-prepared Ppy@Ag/g-C{sub 3}N{sub 4} could remove of various organic pollutants in water. • The enhanced photocatalytic activity of Ppy@Ag/g-C{sub 3}N{sub 4} comes from π conjugated electronic structures of Ppy and Ag species as the electron transfer mediator between Ppy and g-C{sub 3}N{sub 4}. • The Ppy@Ag/g-C{sub 3}N{sub 4} sample also showed a relatively good recycling stability. - Abstract: The ternary conductive Ppy@Ag/g-C{sub 3}N{sub 4} composite photocatalysts was successfully synthesized by polymerization process and surface polymerization technique. And the as-prepared Ppy@Ag/g-C{sub 3}N{sub 4} sample exhibited the higher photocatalytic activity for various pollutant (MO, DM, TC, CIP, GFLX and EH) remove than that of pure g-C{sub 3}N{sub 4} and Ag/g-C{sub 3}N{sub 4} under visible light irradiation. It mainly originated from the Ag nanoparticles anchored between g-C{sub 3}N{sub 4} and Ppy acted as electron transfer mediator that facilitated the charge carrier separation and then expending the lifetime of the carriers. Meanwhile, the obtained Ppy@Ag/g-C{sub 3}N{sub 4} sample also showed a relatively good recycling stability which was the crucial factor for photocatalyst practical application. This work provided a new facile strategy for improving photo-degradation activity of g-C{sub 3}N{sub 4} photocatalyst.

Evaluation of a New Biosensor Based on in Situ Synthesized PPy-Ag-PVP Nanohybrid for Selective Detection of Dopamine.

Science.gov (United States)

Vellaichamy, Balakumar; Periakaruppan, Prakash; Paulmony, Tharmaraj

2017-02-09

In the present work, in situ synthesis of polypyrrole-silver-polyvinylpyrrolidone (PPy-Ag-PVP) nanohybrid using AgNO 3 as an oxidant and polyvinylpyrrolidone (PVP) as a stabilizer and surfactant is demonstrated. The obtained ternary PPy-Ag-PVP nanohybrid was characterized by UV-vis, FT-IR, XRD, Raman, TGA, SEM, and HR-TEM analysis. Further the synthesized PPy-Ag-PVP has been investigated for its selective and sensitive sensing of dopamine (DA). The PPy-Ag-PVP modified glassy carbon electrode shows a reversible electrochemical behavior with superior response for DA. The limit of detection and limit of quantification are found to be 0.0126 and 0.042 μM (S/N = 3 and 10), respectively, with remarkable sensitivity (7.26 μA mM -1 cm -2 ). The practical application of the present modified electrode has been validated by determining the concentration of DA in human urine samples of different age group.

Synthesis and characterization of novel PPy/Bi{sub 2}O{sub 2}CO{sub 3} composite with improved photocatalytic activity for degradation of Rhodamine-B

Energy Technology Data Exchange (ETDEWEB)

Wang, Qizhao, E-mail: wangqizhao@163.com [College of Chemistry and Chemical Engineering, Northwest Normal University, Key Laboratory of Eco-Environment-Related Polymer Materials, Ministry of Education of China, Key Laboratory of Gansu Polymer Materials, Lanzhou 730070 (China); Zheng, Longhui; Chen, Yutao; Fan, Jiafeng [College of Chemistry and Chemical Engineering, Northwest Normal University, Key Laboratory of Eco-Environment-Related Polymer Materials, Ministry of Education of China, Key Laboratory of Gansu Polymer Materials, Lanzhou 730070 (China); Huang, Haohao, E-mail: scuthhh@hotmail.com [College of Materials Science and Engineering, South China University of Technology, Guangzhou 510640 (China); Su, Bitao [College of Chemistry and Chemical Engineering, Northwest Normal University, Key Laboratory of Eco-Environment-Related Polymer Materials, Ministry of Education of China, Key Laboratory of Gansu Polymer Materials, Lanzhou 730070 (China)

2015-07-15

Highlights: • A new photocatalyst PPy/Bi{sub 2}O{sub 2}CO{sub 3} was synthesized by a simple hydrothermal method. • The PPy/Bi{sub 2}O{sub 2}CO{sub 3} photocatalyst shows enhanced degradation activity of RhB under UV light irradiation. • A photocatalytic mechanism is proposed based on the synergistic effect of PPy and Bi{sub 2}O{sub 2}CO{sub 3}. - Abstract: Photocatalyst Bi{sub 2}O{sub 2}CO{sub 3} modified by polypyrrole (PPy) was synthesized via a facile hydrothermal method. As-prepared PPy/Bi{sub 2}O{sub 2}CO{sub 3} composites were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and UV–vis diffuse reflectance spectroscopy (DRS). Presence of PPy did not affect the crystal structure, but exerted great influence on the photocatalytic activity of Bi{sub 2}O{sub 2}CO{sub 3} and enhanced absorption band of pure Bi{sub 2}O{sub 2}CO{sub 3}. The photocatalytic activities of the PPy/Bi{sub 2}O{sub 2}CO{sub 3} samples were determined by photocatalytic degradation of Rhodamine-B (RhB) under ultra violet (UV) irradiation and 0.75 wt.% PPy/Bi{sub 2}O{sub 2}CO{sub 3} composite showed the highest photocatalytic activity. The enhanced photocatalytic performance could be attributed to the synergistic effect of PPy and Bi{sub 2}O{sub 2}CO{sub 3}. A possible photocatalytic mechanism of the PPy/Bi{sub 2}O{sub 2}CO{sub 3} photocatalysts was proposed in order to guide the further improvement of its photocatalytic performance.

GLYX-13 Ameliorates Schizophrenia-Like Phenotype Induced by MK-801 in Mice: Role of Hippocampal NR2B and DISC1

Science.gov (United States)

Zhou, Dongsheng; Lv, Dan; Wang, Zhen; Zhang, Yanhua; Chen, Zhongming; Wang, Chuang

2018-01-01

Background: Evidence supports that the hypofunction of N-methyl-D-aspartate receptor (NMDAR) and downregulation of disrupted-in-schizophrenia 1 (DISC1) contribute to the pathophysiology of schizophrenia. N-Methyl D-aspartate receptor subtype 2B (NR2B)-containing NMDAR are associated with cognitive dysfunction in schizophrenia. GLYX-13 is an NMDAR glycine-site functional partial agonist and cognitive enhancer that does not induce psychotomimetic side effects. However, it remains unclear whether NR2B plays a critical role in the GLYX-13-induced alleviation of schizophrenia-like behaviors in mice. Methods: The effect of GLYX-13 was tested by observing changes in locomotor activity, novel object recognition ability, and prepulse inhibition (PPI) induced by dizocilpine (known as MK-801) in mice. Lentivirus-mediated NR2B knockdown in the hippocampus was assessed to confirm the role of NR2B in GLYX-13 pathophysiology, using Western blots and immunohistochemistry. Results: The systemic administration of GLYX-13 (0.5 and 1 mg/kg, i.p.) ameliorates MK-801 (0.5 mg/kg, i.p.)-induced hyperlocomotion, deficits in memory, and PPI in mice. Additionally, GLYX-13 normalized the MK-801-induced alterations in signaling molecules, including NR2B and DISC1 in the hippocampus. Furthermore, we found that NR2B knockdown produced memory and PPI deficits without any changes in locomotor activity. Notably, DISC1 levels significantly decreased by NR2B knockdown. However, the effective dose of GLYX-13 did not alleviate the memory and PPI dysfunctions or downregulation of DISC1 induced by NR2B knockdown. Conclusion: Our results suggest GLYX-13 as a candidate for schizophrenia treatment, and NR2B and DISC1 in the hippocampus may account for the molecular mechanisms of GLYX-13. PMID:29695955

Discovering functional interdependence relationship in PPI networks for protein complex identification.

Science.gov (United States)

Lam, Winnie W M; Chan, Keith C C

2012-04-01

Protein molecules interact with each other in protein complexes to perform many vital functions, and different computational techniques have been developed to identify protein complexes in protein-protein interaction (PPI) networks. These techniques are developed to search for subgraphs of high connectivity in PPI networks under the assumption that the proteins in a protein complex are highly interconnected. While these techniques have been shown to be quite effective, it is also possible that the matching rate between the protein complexes they discover and those that are previously determined experimentally be relatively low and the "false-alarm" rate can be relatively high. This is especially the case when the assumption of proteins in protein complexes being more highly interconnected be relatively invalid. To increase the matching rate and reduce the false-alarm rate, we have developed a technique that can work effectively without having to make this assumption. The name of the technique called protein complex identification by discovering functional interdependence (PCIFI) searches for protein complexes in PPI networks by taking into consideration both the functional interdependence relationship between protein molecules and the network topology of the network. The PCIFI works in several steps. The first step is to construct a multiple-function protein network graph by labeling each vertex with one or more of the molecular functions it performs. The second step is to filter out protein interactions between protein pairs that are not functionally interdependent of each other in the statistical sense. The third step is to make use of an information-theoretic measure to determine the strength of the functional interdependence between all remaining interacting protein pairs. Finally, the last step is to try to form protein complexes based on the measure of the strength of functional interdependence and the connectivity between proteins. For performance evaluation

Peripubertal exposure to environmental enrichment prevents schizophrenia-like behaviors in the SHR strain animal model.

Science.gov (United States)

Santos, Camila Mauricio; Peres, Fernanda Fiel; Diana, Mariana Cepollaro; Justi, Veronica; Suiama, Mayra Akimi; Santana, Marcela Gonçalves; Abílio, Vanessa Costhek

2016-10-01

Schizophrenia is a highly disabling mental disorder, in which genetics and environmental factors interact culminating in the disease. The treatment of negative symptoms and cognitive deficits with antipsychotics is currently inefficient and is an important field of research. Environmental enrichment (EE) has been suggested to improve some cognitive deficits in animal models of various psychiatric disorders. In this study, we aimed to evaluate a possible beneficial effect of early and long-term exposure to EE on an animal model of schizophrenia, the SHR strain. Young male Wistar rats (control strain) and SHRs (21 post-natal days) were housed for 6weeks in two different conditions: in large cages (10 animals per cage) containing objects of different textures, forms, colors and materials that were changed 3 times/week (EE condition) or in standard cages (5 animals per cage - Control condition). Behavioral evaluations - social interaction (SI), locomotion, prepulse inhibition of startle (PPI) and spontaneous alternation (SA) - were performed 6weeks after the end of EE. SHRs presented deficits in PPI (a sensorimotor impairment), SI (mimicking the negative symptoms) and SA (a working memory deficit), and also hyperlocomotion (modeling the positive symptoms). EE was able to reduce locomotion and increase PPI in both strains, and to prevent the working memory deficit in SHRs. EE also increased the number of neurons in the CA1 and CA3 of the hippocampus. In conclusion, EE can be a potential nonpharmacological strategy to prevent some behavioral deficits associated with schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Quantifying esophagogastric junction contractility with a novel HRM topographic metric, the EGJ-Contractile Integral: normative values and preliminary evaluation in PPI non-responders.

Science.gov (United States)

Nicodème, F; Pipa-Muniz, M; Khanna, K; Kahrilas, P J; Pandolfino, J E

2014-03-01

Despite its obvious pathophysiological relevance, the clinical utility of measures of esophagogastric junction (EGJ) contractility is unsubstantiated. High-resolution manometry (HRM) may improve upon this with its inherent ability to integrate the magnitude of contractility over time and length of the EGJ. This study aimed to develop a novel HRM metric summarizing EGJ contractility and test its ability distinguish among subgroups of proton pump inhibitor non-responders (PPI-NRs). 75 normal controls and 88 PPI-NRs were studied. All underwent HRM. PPI-NRs underwent pH-impedance monitoring on PPI therapy scored in terms of acid exposure, number of reflux events, and reflux-symptom correlation and grouped as meeting all criteria, some criteria, or no criteria of abnormality. Control HRM studies were used to establish normal values for candidate EGJ contractility metrics, which were then compared in their ability to differentiate among PPI-NR subgroups. The EGJ contractile integral (EGJ-CI), a metric integrating contractility across the EGJ for three respiratory cycles, best distinguished the All Criteria PPI-NR subgroup from controls and other PPI-NR subgroups. Normal values (median, [IQR]) for this measure were 39 mmHg-cm [25-55 mmHg-cm]. The correlation between the EGJ-CI and a previously proposed metric, the lower esophageal sphincter-pressure integral, that used a fixed 10 s time frame and an atmospheric as opposed to gastric pressure reference was weak. Among HRM metrics tested, the EGJ-CI was best in distinguishing PPI-NRs meeting all criteria of abnormality on pH-impedance testing. Future prospective studies are required to explore its utility in management of broader groups of gastroesophageal reflux disease patients. © 2013 John Wiley & Sons Ltd.

Decorating MOF-Derived Nanoporous Co/C in Chain-Like Polypyrrole (PPy Aerogel: A Lightweight Material with Excellent Electromagnetic Absorption

Directory of Open Access Journals (Sweden)

Xiaodong Sun

2018-05-01

Full Text Available To clear away the harmful effects of the increment of electromagnetic pollution, high performance absorbers with appropriate impedance matching and strong attenuation capacity are strongly desired. In this study, a chain-like PPy aerogel decorated with MOF-derived nanoporous Co/C (Co/C@PPy has been successfully prepared by a self-assembled polymerization method. With a filler loading ratio of 10 wt %, the composite of Co/C@PPy could achieve a promising electromagnetic absorption performance both in intensity and bandwidth. An optimal reflection loss value of −44.76 dB is achieved, and the effective bandwidth (reflection loss lower than −10 dB is as large as 6.56 GHz. Furthermore, a composite only loaded with 5 wt % Co/C@PPy also achieves an effective bandwidth of 5.20 GHz, which is even better than numerous reported electromagnetic absorption (EA materials. The result reveals that the as-fabricated Co/C@PPy—with high absorption intensity, broad bandwidth, and light weight properties—can be utilized as a competitive absorber.

High Operating Voltage Supercapacitor Using PPy/AC Composite Electrode Based on Simple Dipping Method

Directory of Open Access Journals (Sweden)

Kyoungho Kim

2015-01-01

Full Text Available As various wearable devices are emerging, self-generated power sources, such as piezoelectric generators, triboelectric generators, and thermoelectric generators, are of interest. To adapt self-generated power sources for application devices, a supercapacitor is necessary because of the short generation times (1–10 ms and low generated power (1–100 μW of self-generated power sources. However, to date, supercapacitors are too large to be adapted for wearable devices. There have been many efforts to reduce the size of supercapacitors by using polypyrrole (PPy for high energy supercapacitor electrodes. However, these supercapacitors have several disadvantages, such as a low operating voltage due to the use of an aqueous electrolyte, and complex manufacturing methods, such as the hydrogel and aerosol methods. In particular, the low operating voltage (~1.0 V is a significant issue because most electronic components operate above 3.0 V. In this study, we successfully demonstrated the high operating voltage (3.0 V of a supercapacitor using a PPy/activated carbon (AC composite electrode based on the chemical polymerization of the PPy by simple dipping. In addition, a twofold enhancement of its energy density was achieved compared with conventional supercapacitors using AC electrodes.

Dielectric and AC Conductivity Studies in PPy-Ag Nanocomposites

OpenAIRE

Praveenkumar, K.; Sankarappa, T.; Ashwajeet, J. S.; Ramanna, R.

2015-01-01

Polypyrrole and silver nanoparticles have been synthesized at 277 K by chemical route. Nanoparticles of polypyrrole-silver (PPy-Ag) composites were prepared by mixing polypyrrole and silver nanoparticles in different weight percentages. Dielectric properties as a function of temperature in the range from 300 K to 550 K and frequency in the range from 50 Hz to 1 MHz have been measured. Dielectric constant decreased with increase in frequency and temperature. Dielectric loss decreased with incr...

Immobilization of Tyrosinase from Avocado Crude Extract in Polypyrrole Films for Inhibitive Detection of Benzoic Acid

Directory of Open Access Journals (Sweden)

André Brisolari

2014-07-01

Full Text Available Inhibition-based biosensors were developed by immobilizing tyrosinase (Tyr, polyphenol oxidase from the crude extract of avocado fruit on electrochemically prepared polypyrrole (PPy films. The biosensors were prepared during the electropolymerization of pyrrole in a solution containing a fixed volume of the crude extract of avocado. The dependence of the biosensor responses on the volume used from the crude extract, values of pH and temperature was studied, and a substrate, catechol, at different concentrations, was amperometrically detected by these biosensors. Benzoic acid, a competitive inhibitor of Try, was added to the catechol solutions at specific concentrations aimed at obtaining the inhibition constant, K’m, which ranged from 1.7 to 4.6 mmol∙L−1 for 0.0 and 60 µmol∙L−1 of benzoic acid, respectively. Studies on the inhibition caused by benzoic acid by using PPy/Try films, and catechol as a substrate, allowed us propose how to develop, under optimized conditions, simple and low-cost biosensors based on the use of avocado fruit.

Targeting Hsp90-Cdc37: A Promising Therapeutic Strategy by Inhibiting Hsp90 Chaperone Function.

Science.gov (United States)

Wang, Lei; Li, Li; Gu, Kai; Xu, Xiao-Li; Sun, Yuan; You, Qi-Dong

2017-01-01

The Hsp90 chaperone protein regulates the folding, maturation and stability of a wide variety of oncoproteins. In recent years, many Hsp90 inhibitors have entered into the clinical trials while all of them target ATPase showing similar binding capacity and kinds of side-effects so that none have reached to the market. During the regulation progress, numerous protein- protein interactions (PPI) such as Hsp90 and client proteins or cochaperones are involved. With the Hsp90-cochaperones PPI networks being more and more clear, many cancerous proteins have been reported to be tightly correlated to Hsp90-cochaperones PPI. Among them, Hsp90-Cdc37 PPI has been widely reported to associate with numerous protein kinases, making it a novel target for the treatment of cancers. In this paper, we briefly review the strategies and modulators targeting Hsp90-Cdc37 complex including direct and indirect regulation mechanism. Through these discussions we expect to present inspirations for new insights into an alternative way to inhibit Hsp90 chaperone function. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

True-color 640 ppi OLED arrays patterned by CA i-line photolithography

NARCIS (Netherlands)

Malinowski, P.E.; Ke, T.; Nakamura, A.; Chang, T.-Y.; Gokhale, P.; Steudel, S.; Janssen, D.; Kamochi, Y.; Koyama, I.; Iwai,Y.; Heremans, P.

2015-01-01

In this paper, side-by-side patterning of red, green and blue OLEDs is demonstrated. To achieve 640 ppi arrays with 20 µm subpixel pitch, chemically amplified, i-line photoresist system with submicron resolution was used. These results show feasibility of obtaining full-color displays with

Luminescent sensitization and blue shift emission of Ir(ppy){sub 2}(VPHD) by copolymerization with MMA

Energy Technology Data Exchange (ETDEWEB)

An Baoli, E-mail: blan@staff.shu.edu.cn [Department of Chemistry, College of Science, Shanghai University, Shanghai 200444 (China); Dai Fanzeng; Zhang Yanling; Song Jian; Huang, Xiao-Di [Department of Chemistry, College of Science, Shanghai University, Shanghai 200444 (China); Xu, Jia-Qiang, E-mail: xujiaqiang@shu.edu.cn [Department of Chemistry, College of Science, Shanghai University, Shanghai 200444 (China); State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050 (China)

2011-08-15

Ir(ppy){sub 2}(VPHD) (ppy=2-phenyl pyridine, VPHD=6-(4-vinylphenyl)-2,4-hexanedione) was copolymerized with methyl methacrylate (MMA). The copolymer had high quantum yield of 52.3{+-}0.5% in dilute ethyl acetate solution, and the yield increased around 45% than that of the iridium monomer. The maximum emission peaks for the copolymers shifted from 515 to 489 nm while the iridium complex content was less than 0.005 mol% in the feed. The blue emission at 489 nm and the green emission at 520 nm were analyzed by Lorenz function. They are attributed to {sup 1}MLCT and {sup 3}MLCT emissions, respectively. - Highlights: > PMMA-Ir(ppy){sub 2}(VPHD) as luminescent material with high yield of 53%. > The blue color emission at 489 nm from {sup 1}MLCT in conformity with Lorenz function. > The quantum yield for the copolymer increases 45% than that of the iridium monomer. > The {sup 3}MLCT Ex. intensity versus the monomer concentration is in conformity with Boltzmann function.

Fabricate BC/Fe3O4@PPy 3D nanofiber film as flexible electrode for supercapacitor application

Science.gov (United States)

Lv, Xvdan; Li, Guohui; Pang, Zengyuan; Li, Dawei; Lei, Luo; Lv, Pengfei; Mushtaq, Muhammad; Wei, Qufu

2018-05-01

For flexible film supercapacitor, high areal capacitance is a main evaluating indicator. In this paper, bacterial cellulose (BC) with special three-dimensional structure was used as the natural flexible base material. Fe3O4 nanoparticles with average diameter of 20 nm were synthesized on the surface of BC fibers. The conductive path polypyrrole (PPy) was introduced as shell of BC/Fe3O4 fibers to further improve the pseudo capacitance in 1 mol/L H2SO4 solution. Besides, the BC/Fe3O4@PPy was used for supercapacitor application in acid electrolyte, and delivered higher areal capacitance compared to other Fe3O4 composites in previous reports. The obtained BC/Fe3O4@PPy film showed excellent mechanical strength (tensile strength reached 11 MPa), high areal specific capacitance (5.4 F cm-2 at active mass of 8.4 mg cm-2), and long cycle life (1.95 F cm-2 over 3500 cycles).

Choice vs. voice? PPI policies and the re-positioning of the state in England and Wales.

Science.gov (United States)

Hughes, David; Mullen, Caroline; Vincent-Jones, Peter

2009-09-01

CONTEXT AND THESIS: Changing patient and public involvement (PPI) policies in England and Wales are analysed against the background of wider National Health Service (NHS) reforms and regulatory frameworks. We argue that the growing divergence of health policies is accompanied by a re-positioning of the state vis-à-vis PPI, characterized by different mixes of centralized and decentralized regulatory instruments. Analysis of legislation and official documents, and interviews with policy makers. In England, continued hierarchical control is combined with the delegation of responsibilities for the oversight and organization of PPI to external institutions such as the Care Quality Commission and local involvement networks, in support of the government's policy agenda of increasing marketization. In Wales, which has rejected market reforms and economic regulation, decentralization is occurring through the use of mixed regulatory approaches and networks suited to the small-country governance model, and seeks to benefit from the close proximity of central and local actors by creating new forms of engagement while maintaining central steering of service planning. Whereas English PPI policies have emerged in tandem with a pluralistic supply-side market and combine new institutional arrangements for patient 'choice' with other forms of involvement, the Welsh policies focus on 'voice' within a largely publicly-delivered service. While the English reforms draw on theories of economic regulation and the experience of independent regulation in the utilities sector, the Welsh model of local service integration has been more influenced by reforms in local government. Such transfers of governance instruments from other public service sectors to the NHS may be problematic.

Delocalization of π electrons and trapping action of ZnO nanoparticles in PPY matrix for hybrid solar cell application

Science.gov (United States)

Singh, Rajinder; Choudhary, Ram Bilash; Kandulna, Rohit

2018-03-01

Polypyrrole (PPY)-Zinc Oxide (ZnO) nanocomposites with varying concentration of ZnO (1:1-1:4) were prepared via in-situ polymerization technique by using pyrrole monomer in the presence of ammonium persulphate (APS) as oxidant. Globular morphology of PPY and sheet like structure of ZnO was examined using FESEM and EDAX. FTIR showed the presence of vibration modes in fingerprint region (1500 cm-1-500 cm-1) for metal oxides confirming the presence and interaction of ZnO with the polymer matrix in nanocomposites. Amorphous nature of PPY and hexagonal wurtzite structure of ZnO was confirmed using XRD with average crystallite size within 20 nm-30 nm. PANI-ZnO (1:1) exhibited blue shift in comparison to PPY (neat) and optimized optical band gap ∼ 1.81 eV. The effect of carrier concentration was investigated using electrochemical analyzer and maximum current was recorded for PANI-ZnO (1:1). The highest conductance was calculated for PANI-ZnO (1:1) ∼ 7.3242 × 10-3 S using current -voltage characteristics. Thermal stability was found to be increasing with the increase in ZnO concentration PANI-ZnO nanocomposite.

Prenatal phencyclidine treatment induces behavioral deficits through impairment of GABAergic interneurons in the prefrontal cortex.

Science.gov (United States)

Toriumi, Kazuya; Oki, Mika; Muto, Eriko; Tanaka, Junko; Mouri, Akihiro; Mamiya, Takayoshi; Kim, Hyoung-Chun; Nabeshima, Toshitaka

2016-06-01

We previously reported that prenatal treatment with phencyclidine (PCP) induces glutamatergic dysfunction in the prefrontal cortex (PFC), leading to schizophrenia-like behavioral deficits in adult mice. However, little is known about the prenatal effect of PCP treatment on other types of neurons. We focused on γ-aminobutyric acid (GABA)-ergic interneurons and evaluated the effect of prenatal PCP exposure on the neurodevelopment of GABAergic interneurons in the PFC. PCP was administered at the dose of 10 mg/kg/day to pregnant dams from embryonic day 6.5 to 18.5. After the pups were reared to adult, we analyzed their GABAergic system in the PFC using immunohistological, biochemical, and behavioral analyses in adulthood. The prenatal PCP treatment decreased the density of parvalbumin-positive cells and reduced the expression level of glutamic acid decarboxylase 67 (GAD67) and GABA content of the PFC in adults. Additionally, prenatal PCP treatment induced behavioral deficits in adult mice, such as hypersensitivity to PCP and prepulse inhibition (PPI) deficits. These behavioral deficits were ameliorated by pretreatment with the GABAB receptor agonist baclofen. Furthermore, the density of c-Fos-positive cells was decreased after the PPI test in the PFC of mice treated with PCP prenatally, and this effect was ameliorated by pretreatment with baclofen. These findings suggest that prenatal treatment with PCP induced GABAergic dysfunction in the PFC, which caused behavioral deficits.

Does prenatal valproate interact with a genetic reduction in the serotonin transporter?A rat study on anxiety and cognition

Directory of Open Access Journals (Sweden)

Bart A Ellenbroek

2016-09-01

Full Text Available There is ample evidence that prenatal exposure to valproate (or valproic acid, VPA enhances the risk of developing Autism Spectrum Disorders (ASD. In line with this, a single injection of VPA induces a multitude of ASD-like symptoms in animals such as rats and mice. However, there is equally strong evidence that genetic factors contribute significantly to the risk of ASD and indeed, like most other psychiatric disorders, ASD is now generally thought to results from an interaction between genetic and environmental factors. Given that VPA significantly impacts on the serotonergic system, and serotonin has strong biochemical and genetic links to ASD, we aimed to investigate the interaction between genetic reduction in the serotonin transporter and prenatal valproate administration. More specifically, we exposed both wildtype (SERT+/+ rats and rats heterozygous for the serotonin transporter deletion (SERT+/- to a single injection of 400 mg/kg VPA at gestational day (GD 12. The offspring, in adulthood, was assessed in four different tests: Elevated Plus Maze and Novelty Suppressed Feeding as measures for anxiety and prepulse inhibition (PPI and latent inhibition as measures for cognition and information processing. The results show that prenatal VPA significantly increased anxiety in both paradigm, reduced PPI and reduced conditioning in the latent inhibition paradigm. However, we failed to find a significant gene – environment interaction. We propose that this may be related to the timing of the VPA injection and suggest that whereas GD12 might be optimal for affecting normal rat, rats with a genetically compromised serotonergic system may be more sensitive to VPA at earlier time points during gestation. Overall our data are the first to investigate gene * environmental interactions in a genetic rat model for ASD suggest that timing may be of crucial importance to the long-term outcome.

The prototypical ranitidine analog JWS-USC-75-IX improves information processing and cognitive function in animal models.

Science.gov (United States)

Terry, Alvin V; Buccafusco, Jerry J; Herman, Elizabeth J; Callahan, Patrick M; Beck, Wayne D; Warner, Samantha; Vandenhuerk, Leah; Bouchard, Kristy; Schwarz, Gary M; Gao, Jie; Chapman, James M

2011-03-01

This study was designed to evaluate further a prototypical ranitidine analog, JWS-USC-75-IX, [(3-[[[2-[[(5-dimethylaminomethyl)-2-furanyl]methyl]thio]ethyl]amino]-4-nitropyridazine, JWS], for neuropharmacologic properties that would theoretically be useful for treating cognitive and noncognitive behavioral symptoms of neuropsychiatric disorders. JWS was previously found to inhibit acetylcholinesterase (AChE) activity, serve as a potent ligand at muscarinic M₂ acetylcholine receptors, and elicit positive effects on spatial learning, passive avoidance, and working memory in rodents. In the current study, JWS was evaluated for binding activity at more than 60 neurotransmitter receptors, transporters, and ion channels, as well as for inhibitory activity at AChE and butyrylcholinesterase (BChE). The results indicate that JWS inhibits AChE and BChE at low (micromolar) concentrations and that it is a functional antagonist at M₂ receptors (K(B) = 320 nM). JWS was subsequently evaluated orally across additional behavioral assays in rodents (dose range, 0.03-10.0 mg/kg) as well as nonhuman primates (dose range, 0.05-2.0 mg/kg). In rats, JWS improved prepulse inhibition (PPI) of the acoustic startle response in nonimpaired rats and attenuated PPI deficits in three pharmacologic impairment models. JWS also attenuated scopolamine and (-)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801)-related impairments in a spontaneous novel object recognition task and a five-choice serial reaction time task, respectively. In monkeys, JWS elicited dose-dependent improvements of a delayed match-to-sample task as well as an attention-related version of the task where randomly presented (task-relevant) distractors were presented. Thus, JWS (potentially via effects at several drug targets) improves information processing, attention, and memory in animal models and could potentially treat the cognitive and behavioral symptoms of some neuropsychiatric illnesses.

Synthesis and characterization of LDH/Ppi composite and its application as adsorbent of 2,4-dichlorophenoxyacetic (herbicide); Sintese e caracterizacao do composito HDL/Ppi e sua aplicacao como adsorvente do 2,4-diclorofenoxiacetico (herbicida)

Energy Technology Data Exchange (ETDEWEB)

Pacheco, I.S.; Oliveira, R.S.; Girotto, L.G.; Freitas, L.L. de; Amaral, F.A. do; Canobre, S.C., E-mail: ingrid_1194@hotmail.com [Universidade Federal de Uberlandia (UFU), MG (Brazil). Instituto de Quimica

2016-07-01

This work had as main objective the synthesis and characterization of LDH [Co-Al-Cl] method by hydrolysis of urea and then its synthesized polypyrrole coating by chemically targeting the application as adsorbent dichlorophenoxyacetic acid (2,4-D). The x-ray diffractogram of well defined showed diffraction peaks corresponding to the planes 003, 006, 009 and 110 which allow them to rhombohedral indexes and lamellar structure. The composite LDH / Ppi had a percentage of 49% herbicide retention in aqueous solution. From the investigated adsorption isotherm models that more fit the experimental data was the Freundlich, so it could be inferred that the interaction between the LDH / Ppi and the herbicide was physical, ie an rapid, reversible adsorption and does not specify. (author)

44-1: Invited Paper: Photolithography as Enabler of AMOLED Displays Beyond 1000 ppi

NARCIS (Netherlands)

Malinowski, P.E.; Ke, T.; Nakamura, A.; Vicca, P.; Kronemeijer, A.J.; Ameys, M.; Steen, J.L. van der; Steudel, S.; Kamochi, Y.; Iwai, Y.; Gelinck, G.; Heremans, P.

2017-01-01

This paper describes the potential of hi-res display fabrication using OLED photolithography. We demonstrate 1250 ppi multicolor arrays, pixel scaling down to 3 μm pitch, integration in active displays, and improving lifetime after patterning (200 hours T75, smOLEDs). Photolithography can enable

Histomorphological differentiation of non-erosive reflux disease and functional heartburn in patients with PPI-refractory heartburn.

Science.gov (United States)

Kandulski, A; Jechorek, D; Caro, C; Weigt, J; Wex, T; Mönkemüller, K; Malfertheiner, P

2013-09-01

Proton pump inhibitor (PPI)-refractory heartburn may be due to persistent gastro-oesophageal reflux, oesophageal hypersensitivity or functional heartburn (FH). The differentiation between non-erosive reflux disease (NERD) and FH may be very difficult. However, this differentiation is important for appropriate therapeutic management. Dilated intercellular spaces (DIS), papillary elongation (PE) and basal cell hyperplasia (BCH) can be all assessed by light microscopy. Whether these mucosal abnormalities allow the differentiation of NERD from FH in PPI-refractory patients is uncertain. To assess histopathological findings by light microscopy in patients with refractory heartburn to differentiate NERD from FH. Sixty-two patients with PPI-refractory symptoms underwent EGD and MII-pH after pausing PPI medication for 2 weeks before investigation. Twenty-five subjects without upper gastrointestinal symptoms were included as controls. Symptom assessment was based on the reflux disease questionnaire (RDQ). Biopsies were taken 3-5 cm above the gastro-oesophageal junction. DIS, PE, BCH and infiltration of immune cells were evaluated and a sum score was calculated. Based on endoscopy and MII-pH, GERD was diagnosed in 43 patients (NERD: 20; ERD: 23) and FH in 19 patients. There was no difference in symptoms between the groups. Each individual histopathological item was different between the groups (P < 0.0001). Between NERD and FH, the most significant difference was found for DIS and the histopathological sum score (P < 0.001). These findings suggest that oesophageal biopsies are useful to differentiate NERD from FH. Increased DIS and a histological sum score are the most significant histopathological abnormalities in NERD as compared with FH. © 2013 John Wiley & Sons Ltd.

Choice vs. voice? PPI policies and the re‐positioning of the state in England and Wales

Science.gov (United States)

Hughes, David; Mullen, Caroline; Vincent‐Jones, Peter

2009-01-01

Abstract Context and Thesis  Changing patient and public involvement (PPI) policies in England and Wales are analysed against the background of wider National Health Service (NHS) reforms and regulatory frameworks. We argue that the growing divergence of health policies is accompanied by a re‐positioning of the state vis‐à‐vis PPI, characterized by different mixes of centralized and decentralized regulatory instruments. Method  Analysis of legislation and official documents, and interviews with policy makers. Findings  In England, continued hierarchical control is combined with the delegation of responsibilities for the oversight and organization of PPI to external institutions such as the Care Quality Commission and local involvement networks, in support of the government’s policy agenda of increasing marketization. In Wales, which has rejected market reforms and economic regulation, decentralization is occurring through the use of mixed regulatory approaches and networks suited to the small‐country governance model, and seeks to benefit from the close proximity of central and local actors by creating new forms of engagement while maintaining central steering of service planning. Whereas English PPI policies have emerged in tandem with a pluralistic supply‐side market and combine new institutional arrangements for patient ‘choice’ with other forms of involvement, the Welsh policies focus on ‘voice’ within a largely publicly‐delivered service. Discussion  While the English reforms draw on theories of economic regulation and the experience of independent regulation in the utilities sector, the Welsh model of local service integration has been more influenced by reforms in local government. Such transfers of governance instruments from other public service sectors to the NHS may be problematic. PMID:19754688

Immobilization of Trichoderma harzianum α-amylase on PPyAgNp/Fe3O4-nanocomposite: chemical and physical properties.

Science.gov (United States)

Mohamed, Saleh A; Al-Harbi, Majed H; Almulaiky, Yaaser Q; Ibrahim, Ibrahim H; Salah, Hala A; El-Badry, Mohamed O; Abdel-Aty, Azza M; Fahmy, Afaf S; El-Shishtawy, Reda M

2018-03-26

In this study, a new support has been developed by immobilization of α-amylase onto modified magnetic Fe 3 O 4 -nanoparticles. The characterization of soluble and immobilized α-amylases with regards to kinetic parameters, pH, thermal stability and reusability was studied. The effect of polypyrrole/silver nanocomposite (PPyAgNp) percentage on weight of Fe 3 O 4 and pH on the immobilization of α-amylase was studied. The highest immobilization efficiency (75%) was detected at 10% PPyAgNp/Fe 3 O 4 -nanocomposite and pH 7.0. Immobilization of α-amylase on PPyAgNp/Fe 3 O 4 -nanocomposite was characterized by FT-IR spectroscopy and scanning electron microscopy. The reusability of the immobilized enzyme activity was 80% of its initial activity after 10 reuses. The immobilized enzyme was more stable towards pH, temperature and metal ions compared with soluble enzyme. The kinetic study appeared higher affinity of immobilized enzyme (K m 2.5 mg starch) compared with soluble enzyme (K m 3.5 mg starch). In conclusion, the immobilization of α-amylase on PPyAgNp/Fe 3 O 4 -nanocomposite could successfully be used in industrial and medical applications.

The influence of plasma density decreasement by pre-pulse on the laser wakefield acceleration

Directory of Open Access Journals (Sweden)

Ke-Gong Dong

2011-12-01

Full Text Available In the laser wakefield acceleration, the generation of electron beam is very sensitive to the plasma density. Not only the laser-wakefield interaction, but also the electron trapping and acceleration would be effected by the plasma density. However, the plasma density could be changed in the experiment by different reasons, which will result in the mismatch of parameters arranged initially. Forward Raman scattering spectrum demonstrated that the interaction density was decreased obviously in the experiment, which was verified by the pre-pulse conditions and two-dimensional particle-in-cell simulations. It was demonstrated that the plasma density was very important on the self-evolutions and energy coupling of laser pulse and wakefield, and eventually the energy spectrum of electron beam.

Effects of GABA-B receptor positive modulator on ketamine-induced psychosis-relevant behaviors and hippocampal electrical activity in freely moving rats.

Science.gov (United States)

Ma, Jingyi; Stan Leung, L

2017-10-01

Decreased GABA B receptor function is proposed to mediate some symptoms of schizophrenia. In this study, we tested the effect of CGP7930, a GABA B receptor positive allosteric modulator, on ketamine-induced psychosis-relevant behaviors and hippocampal electrical activity in behaving rats. Electrodes were bilaterally implanted into the hippocampus, and cannulae were placed into the lateral ventricles of Long-Evans rats. CGP7930 or vehicle was injected intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.), alone or 15 min prior to ketamine (3 mg/kg, subcutaneous) injection. Paired click auditory evoked potentials in the hippocampus (AEP), prepulse inhibition (PPI), and locomotor activity were recorded before and after drug injection. CGP7930 at doses of 1 mg/kg (i.p.) prevented ketamine-induced deficit of PPI. CGP7930 (1 mg/kg i.p.) also prevented the decrease in gating of hippocampal AEP and the increase in hippocampal gamma (65-100 Hz) waves induced by ketamine. Unilateral i.c.v. infusion of CGP7930 (0.3 mM/1 μL) also prevented the decrease in gating of hippocampal AEP induced by ketamine. Ketamine-induced behavioral hyperlocomotion was suppressed by 5 mg/kg i.p. CGP7930. CGP7930 alone, without ketamine, did not significantly affect integrated PPI, locomotion, gating of hippocampal AEP, or gamma waves. CGP7930 (1 mg/kg i.p.) increased heterosynaptically mediated paired pulse depression in the hippocampus, a measure of GABA B receptor function in vivo. CGP7930 reduces the behavioral and electrophysiological disruptions induced by ketamine in animals, and the hippocampus may be one of the neural targets where CGP7930 exerts its actions.

Phenotypic effects of maternal immune activation and early postnatal milieu in mice mutant for the schizophrenia risk gene neuregulin-1.

Science.gov (United States)

O'Leary, C; Desbonnet, L; Clarke, N; Petit, E; Tighe, O; Lai, D; Harvey, R; Waddington, J L; O'Tuathaigh, C

2014-09-26

Risk of schizophrenia is likely to involve gene × environment (G × E) interactions. Neuregulin 1 (NRG1) is a schizophrenia risk gene, hence any interaction with environmental adversity, such as maternal infection, may provide further insights into the basis of the disease. This study examined the individual and combined effects of prenatal immune activation with polyriboinosinic-polyribocytidilic acid (Poly I:C) and disruption of the schizophrenia risk gene NRG1 on the expression of behavioral phenotypes related to schizophrenia. NRG1 heterozygous (NRG1 HET) mutant breeding pairs were time-mated. Pregnant dams received a single injection (5mg/kg i.p.) of Poly I:C or vehicle on gestation day 9 (GD9). Offspring were then cross-fostered to vehicle-treated or Poly I:C-treated dams. Expression of schizophrenia-related behavioral endophenotypes was assessed at adolescence and in adulthood. Combining NRG1 disruption and prenatal environmental insult (Poly I:C) caused developmental stage-specific deficits in social behavior, spatial working memory and prepulse inhibition (PPI). However, combining Poly I:C and cross-fostering produced a number of behavioral deficits in the open field, social behavior and PPI. This became more complex by combining NRG1 deletion with both Poly I:C exposure and cross-fostering, which had a robust effect on PPI. These findings suggest that concepts of G × E interaction in risk of schizophrenia should be elaborated to multiple interactions that involve individual genes interacting with diverse biological and psychosocial environmental factors over early life, to differentially influence particular domains of psychopathology, sometimes over specific stages of development. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Search for $B_c^+$ decays to the $p\\overline p\\pi^+$ final state

CERN Document Server

Aaij, Roel; Adeva, Bernardo; Adinolfi, Marco; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Andreassi, Guido; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; d'Argent, Philippe; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baker, Sophie; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Bel, Lennaert; Bellee, Violaine; Belloli, Nicoletta; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bertolin, Alessandro; Betti, Federico; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bifani, Simone; Billoir, Pierre; Bird, Thomas; Birnkraut, Alex; Bizzeti, Andrea; Blake, Thomas; Blanc, Frédéric; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borgheresi, Alessio; Borghi, Silvia; Borisyak, Maxim; Borsato, Martino; Boubdir, Meriem; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Braun, Svende; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Buchanan, Emma; Burr, Christopher; Bursche, Albert; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Campana, Pierluigi; Campora Perez, Daniel; Capriotti, Lorenzo; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carniti, Paolo; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cavallero, Giovanni; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chatzikonstantinidis, Georgios; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu-Faye; Chrzaszcz, Marcin; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Cogoni, Violetta; Cojocariu, Lucian; Collazuol, Gianmaria; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coombes, Matthew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Crocombe, Andrew; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dall'Occo, Elena; Dalseno, Jeremy; David, Pieter; Davis, Adam; De Aguiar Francisco, Oscar; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Simone, Patrizia; Dean, Cameron Thomas; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Déléage, Nicolas; Demmer, Moritz; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Dey, Biplab; Di Canto, Angelo; Di Ruscio, Francesco; Dijkstra, Hans; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dovbnya, Anatoliy; Dreimanis, Karlis; Dufour, Laurent; Dujany, Giulio; Dungs, Kevin; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Egede, Ulrik; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; El Rifai, Ibrahim; Elsasser, Christian; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Färber, Christian; Farley, Nathanael; Farry, Stephen; Fay, Robert; Fazzini, Davide; Ferguson, Dianne; Fernandez Albor, Victor; Ferrari, Fabio; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fleuret, Frederic; Fohl, Klaus; Fontana, Marianna; Fontanelli, Flavio; Forshaw, Dean Charles; Forty, Roger; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Fu, Jinlin; Furfaro, Emiliano; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; García Pardiñas, Julián; Garra Tico, Jordi; Garrido, Lluis; Garsed, Philip John; Gascon, David; Gaspar, Clara; Gavardi, Laura; Gazzoni, Giulio; Gerick, David; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianì, Sebastiana; Gibson, Valerie; Girard, Olivier Göran; Giubega, Lavinia-Helena; Gligorov, V.V.; Göbel, Carla; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graverini, Elena; Graziani, Giacomo; Grecu, Alexandru; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gui, Bin; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Hadavizadeh, Thomas; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; He, Jibo; Head, Timothy; Heister, Arno; Hennessy, Karol; Henrard, Pierre; Henry, Louis; Hernando Morata, Jose Angel; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hoballah, Mostafa; Hombach, Christoph; Hongming, Li; Hulsbergen, Wouter; Humair, Thibaud; Hushchyn, Mikhail; Hussain, Nazim; Hutchcroft, David; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jawahery, Abolhassan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Karbach, Moritz; Karodia, Sarah; Kecke, Matthieu; Kelsey, Matthew; Kenyon, Ian; Kenzie, Matthew; Ketel, Tjeerd; Khairullin, Egor; Khanji, Basem; Khurewathanakul, Chitsanu; Kirn, Thomas; Klaver, Suzanne; Klimaszewski, Konrad; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Kozeiha, Mohamad; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krokovny, Pavel; Kruse, Florian; Krzemien, Wojciech; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kuonen, Axel Kevin; Kurek, Krzysztof; Kvaratskheliya, Tengiz; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Lefèvre, Regis; Leflat, Alexander; Lefrançois, Jacques; Lemos Cid, Edgar; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Yiming; Likhomanenko, Tatiana; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Liu, Xuesong; Loh, David; Longstaff, Iain; Lopes, Jose; Lucchesi, Donatella; Lucio Martinez, Miriam; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Lusardi, Nicola; Lusiani, Alberto; Lyu, Xiao-Rui; Machefert, Frederic; Maciuc, Florin; Maev, Oleg; Maguire, Kevin; Malde, Sneha; Malinin, Alexander; Manca, Giulia; Mancinelli, Giampiero; Manning, Peter Michael; Mapelli, Alessandro; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Marks, Jörg; Martellotti, Giuseppe; Martin, Morgan; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massacrier, Laure Marie; Massafferri, André; Matev, Rosen; Mathad, Abhijit; Mathe, Zoltan; Matteuzzi, Clara; Mauri, Andrea; Maurin, Brice; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; Meadows, Brian; Meier, Frank; Meissner, Marco; Melnychuk, Dmytro; Merk, Marcel; Merli, Andrea; Michielin, Emanuele; Milanes, Diego Alejandro; Minard, Marie-Noelle; Mitzel, Dominik Stefan; Molina Rodriguez, Josue; Monroy, Ignacio Alberto; Monteil, Stephane; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Müller, Dominik; Müller, Janine; Müller, Katharina; Müller, Vanessa; Mussini, Manuel; Muster, Bastien; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nandi, Anita; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen-Mau, Chung; Niess, Valentin; Nieswand, Simon; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Novoselov, Alexey; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Ogilvy, Stephen; Okhrimenko, Oleksandr; Oldeman, Rudolf; Onderwater, Gerco; Osorio Rodrigues, Bruno; Otalora Goicochea, Juan Martin; Otto, Adam; Owen, Patrick; Oyanguren, Maria Aranzazu; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Pappenheimer, Cheryl; Parker, William; Parkes, Christopher; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pearce, Alex; Pellegrino, Antonio; Penso, Gianni; Pepe Altarelli, Monica; Perazzini, Stefano; Perret, Pascal; Pescatore, Luca; Petridis, Konstantinos; Petrolini, Alessandro; Petruzzo, Marco; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pikies, Malgorzata; Pinci, Davide; Pistone, Alessandro; Piucci, Alessio; Playfer, Stephen; Plo Casasus, Maximo; Poikela, Tuomas; Polci, Francesco; Poluektov, Anton; Polyakov, Ivan; Polycarpo, Erica; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Price, Eugenia; Price, Joseph David; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Quagliani, Renato; Rachwal, Bartolomiej; Rademacker, Jonas; Rama, Matteo; Ramos Pernas, Miguel; Rangel, Murilo; Raniuk, Iurii; Raven, Gerhard; Redi, Federico; Reichert, Stefanie; dos Reis, Alberto; Renaudin, Victor; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vincente; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Lopez, Jairo Alexis; Rodriguez Perez, Pablo; Rogozhnikov, Alexey; Roiser, Stefan; Romanovsky, Vladimir; Romero Vidal, Antonio; Ronayne, John William; Rotondo, Marcello; Ruf, Thomas; Ruiz Valls, Pablo; Saborido Silva, Juan Jose; Sagidova, Naylya; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santimaria, Marco; Santovetti, Emanuele; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrina, Darya; Schael, Stefan; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmelzer, Timon; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schubiger, Maxime; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Semennikov, Alexander; Sergi, Antonino; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Siddi, Benedetto Gianluca; Silva Coutinho, Rafael; Silva de Oliveira, Luiz Gustavo; Simi, Gabriele; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Eluned; Smith, Iwan Thomas; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Soomro, Fatima; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Stefkova, Slavomira; Steinkamp, Olaf; Stenyakin, Oleg; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szumlak, Tomasz; T'Jampens, Stephane; Tayduganov, Andrey; Tekampe, Tobias; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Tolk, Siim; Tomassetti, Luca; Tonelli, Diego; Topp-Joergensen, Stig; Tournefier, Edwige; Tourneur, Stephane; Trabelsi, Karim; Traill, Murdo; Tran, Minh Tâm; Tresch, Marco; Trisovic, Ana; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vacca, Claudia; Vagnoni, Vincenzo; Valat, Sebastien; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vázquez Sierra, Carlos; Vecchi, Stefania; van Veghel, Maarten; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Volkov, Vladimir; Vollhardt, Achim; Voong, David; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; de Vries, Jacco; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wang, Jianchun; Ward, David; Watson, Nigel; Websdale, David; Weiden, Andreas; Whitehead, Mark; Wicht, Jean; Wilkinson, Guy; Wilkinson, Michael; Williams, Mark Richard James; Williams, Matthew; Williams, Mike; Williams, Timothy; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wraight, Kenneth; Wright, Simon; Wyllie, Kenneth; Xie, Yuehong; Xu, Zhirui; Yang, Zhenwei; Yin, Hang; Yu, Jiesheng; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Yanxi; Zhelezov, Alexey; Zheng, Yangheng; Zhokhov, Anatoly; Zhong, Liang; Zhukov, Valery; Zucchelli, Stefano

2016-08-10

A search for the decays of the $B_c^+$ meson to $p\\overline p\\pi^+$ is performed for the first time using a data sample corresponding to an integrated luminosity of 3.0 $\\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. No signal is found and an upper limit, at 95$\\%$ confidence level, is set, $\\frac{f_c}{f_u}\\times\\mathcal{B}(B_c^+\\to p\\overline p\\pi^+)<3.6\\times10^{-8}$ in the kinematic region $m(p\\overline p)<2.85\\mathrm{\\,Ge\\kern -0.1em V\\!/}c^2$, $p_{\\rm T}(B)<20\\mathrm{\\,Ge\\kern -0.1em V\\!/}c$ and $2.0< {y}(B)<4.5$, where $\\mathcal{B}$ is the branching fraction and $f_c$ ($f_u$) is the fragmentation fraction of the $b$ quark into a $B_c^+$ ($B^+$) meson.

The D1CT-7 mouse model of Tourette syndrome displays sensorimotor gating deficits in response to spatial confinement.

Science.gov (United States)

Godar, Sean C; Mosher, Laura J; Strathman, Hunter J; Gochi, Andrea M; Jones, Cori M; Fowler, Stephen C; Bortolato, Marco

2016-07-01

The D1CT-7 mouse is one of the best known animal models of Tourette syndrome (TS), featuring spontaneous tic-like behaviours sensitive to standard TS therapies; these characteristics ensure a high face and predictive validity of this model, yet its construct validity remains elusive. To address this issue, we studied the responses of D1CT-7 mice to two critical components of TS pathophysiology: the exacerbation of tic-like behaviours in response to stress and the presence of sensorimotor gating deficits, which are thought to reflect the perceptual alterations causing the tics. D1CT-7 and wild-type (WT) littermates were subjected to a 20 min session of spatial confinement (SC) within an inescapable, 10 cm wide cylindrical enclosure. Changes in plasma corticosterone levels, tic-like behaviours and other spontaneous responses were measured. SC-exposed mice were also tested for the prepulse inhibition (PPI) of the startle response (a sensorimotor gating index) and other TS-related behaviours, including open-field locomotion, novel object exploration and social interaction and compared with non-confined counterparts. SC produced a marked increase in corticosterone concentrations in both D1CT-7 and WT mice. In D1CT-7, but not WT mice, SC exacerbated tic-like and digging behaviours, and triggered PPI deficits and aggressive responses. Conversely, SC did not modify locomotor activity or novel object exploration in D1CT-7 mice. Both tic-like behaviours and PPI impairments in SC-exposed D1CT-7 mice were inhibited by standard TS therapies and D1 dopamine receptor antagonism. These findings collectively support the translational and construct validity of D1CT-7 mice with respect to TS. This article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminergic Systems. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.13/issuetoc. © 2015 The British Pharmacological Society.

Plasma conditions generated by interaction of a high brightness, prepulse free Raman amplified KrF laser pulse with solid targets

International Nuclear Information System (INIS)

Riley, D.; Gizzi, L.A.; Khattak, F.Y.; Mackinnon, A.J.; Viana, S.M.; Willi, O.

1992-01-01

A high brightness, Raman amplified KrF laser has been used to irradiate solid targets with 12 ps laser pulses at intensities above 10 15 W/cm 2 without the presence of a preformed plasma caused by low level amplified spontaneous emission prepulse. Time-resolved x-ray spectroscopy of the K-shell emission from aluminum was used to infer electron densities in excess of 10 23 cm -3 at temperatures of several hundred electronvolts

Fabrication, characterization and gas sensing studies of PPy/MWCNT/SLS nanocomposite

Energy Technology Data Exchange (ETDEWEB)

Tiwari, D. C., E-mail: dctiwari2001@yahoo.com; Atri, Priyanka, E-mail: dctiwari2001@yahoo.com [SOS Electronics, Jiwaji University, Gwalior (M.P.)-474011 (India); Sharma, R. [CSIR-CEERI, Pilani (Rajasthan)-333031 (India)

2014-04-24

Multiwall carbon nanotubes (MWCNT) coated with polypyrrole nanocomposite was prepared by in-situ chemical oxidative polymerization method in the presence of surfactant (SLS). The scanning electron microscope (SEM) pictures indicate the core shell structure of PPy/MWCNT/SLS nanocomposite. Nature of the prepared material was investigated by X-ray diffraction spectroscopy. This nanocomposite shows the excellent gas sensing behaviour for ammonia gas at 150 ppm and 300 ppm levels.

Oral bioavailability of the ether lipid plasmalogen precursor, PPI-1011, in the rabbit: a new therapeutic strategy for Alzheimer's disease

Directory of Open Access Journals (Sweden)

Wood Paul L

2011-12-01

Full Text Available Abstract Introduction Docosahexaenoic acid (DHA and DHA-containing ethanolamine plasmalogens (PlsEtn are decreased in the brain, liver and the circulation in Alzheimer's disease. Decreased supply of plasmalogen precursors to the brain by the liver, as a result of peroxisomal deficits is a process that probably starts early in the AD disease process. To overcome this metabolic compromise, we have designed an orally bioavailable DHA-containing ether lipid precursor of plasmalogens. PPI-1011 is an alkyl-diacyl plasmalogen precursor with palmitic acid at sn-1, DHA at sn-2 and lipoic acid at sn-3. This study outlines the oral pharmacokinetics of this precursor and its conversion to PlsEtn and phosphatidylethanolamines (PtdEtn. Methods Rabbits were dosed orally with PPI-1011 in hard gelatin capsules for time-course and dose response studies. Incorporation into PlsEtn and PtdEtn was monitored by LC-MS/MS. Metabolism of released lipoic acid was monitored by GC-MS. To monitor the metabolic fate of different components of PPI-1011, we labeled the sn-1 palmitic acid, sn-2 DHA and glycerol backbone with13C and monitored their metabolic fates by LC-MS/MS. Results PPI-1011 was not detected in plasma suggesting rapid release of sn-3 lipoic acid via gut lipases. This conclusion was supported by peak levels of lipoic acid metabolites in the plasma 3 hours after dosing. While PPI-1011 did not gain access to the plasma, it increased circulating levels of DHA-containing PlsEtn and PtdEtn. Labeling experiments demonstrated that the PtdEtn increases resulted from increased availability of DHA released via remodeling at sn-2 of phospholipids derived from PPI-1011. This release of DHA peaked at 6 hrs while increases in phospholipids peaked at 12 hr. Increases in circulating PlsEtn were more complex. Labeling experiments demonstrated that increases in the target PlsEtn, 16:0/22:6, consisted of 2 pools. In one pool, the intact precursor received a sn-3

Seven-day PPI-triple therapy with levofloxacin is very effective for Helicobacter pylori eradication.

NARCIS (Netherlands)

Schrauwen, R.W.; Janssen, M.J.R.; Boer, W.A. de

2009-01-01

BACKGROUND: Helicobacter pylori infection causes lifelong gastritis and is associated with the development of peptic ulcer disease, MALT lymphoma and gastric cancer. Many patients benefit from H. pylori eradication therapy. PPI-triple therapy is recommended as initial therapy. Quadruple therapy,

A solid state actuator based on polypyrrole (PPy) and a solid electrolyte NBR working in air

Science.gov (United States)

Cho, Misuk; Nam, Jaedo; Choi, Hyouk Ryeol; Koo, Jachoon; Lee, Youngkwan

2005-05-01

The solid polymer electrolyte based conducting polymer actuator was presented. In the preparation of acutuator module, an ionic liquid impregnated a synthetic rubber (NBR) and PPy were used as a solid polymer electrolyte and conducting polymer, respectively. An ionic liquid, 1-butyl-3-methylimidazolium bis (trifluoromethyl sulfonyl)imide (BMITFSI) is gradually dispersed into the NBR film and the conducting polymer, PPy was synthesized on the surface of NBR. The ionic conductivity of new type solid polymer electrolyte as a function of the immersion time was investigated. The cyclic voltammetry responsed and the redox switching dynamics of PEDOT in NBR matrix were studied. The displacement of the actuator was measured by laser beam.

Facile Synthesis of SrCO3-Sr(OH2/PPy Nanocomposite with Enhanced Photocatalytic Activity under Visible Light

Directory of Open Access Journals (Sweden)

Alfredo Márquez-Herrera

2016-01-01

Full Text Available Pyrrole monomer was chemically polymerized onto SrCO3-Sr(OH2 powders to obtain SrCO3-Sr(OH2/polypyrrole nanocomposite to be used as a candidate for photocatalytic degradation of methylene blue dye (MB. The material was characterized by Fourier transform infrared (FTIR spectroscopy, UV/Vis spectroscopy, and X-ray diffraction (XRD. It was observed from transmission electronic microscopy (TEM analysis that the reported synthesis route allows the production of SrCO3-Sr(OH2 nanoparticles with particle size below 100 nm which were embedded within a semiconducting polypyrrole matrix (PPy. The SrCO3-Sr(OH2 and SrCO3-Sr(OH2/PPy nanocomposites were tested in the photodegradation of MB dye under visible light irradiation. Also, the effects of MB dye initial concentration and the catalyst load on photodegradation efficiency were studied and discussed. Under the same conditions, the efficiency of photodegradation of MB employing the SrCO3-Sr(OH2/PPy nanocomposite increases as compared with that obtained employing the SrCO3-Sr(OH2 nanocomposite.

Combining PPI with qualitative research to engage 'harder-to-reach' populations: service user groups as co-applicants on a platform study for a trial.

Science.gov (United States)

Morgan, Heather; Thomson, Gill; Crossland, Nicola; Dykes, Fiona; Hoddinott, Pat

2016-01-01

It is recommended that research studies are carried out with or by patients and the public through their involvement from the beginning and in as many stages as possible (known as PPI). Some studies formally invite patients and the public to participate in interviews and focused group discussions to collect views about topics (known as qualitative research). In our study on financial incentives for giving up smoking in pregnancy and breastfeeding, we combined both PPI and qualitative research to include the views of women with a range of experiences of smoking and breastfeeding. We involved two mother and baby groups in disadvantaged areas of North East Scotland and North West England as research partners on our team. First, we asked members to comment on our research plans and documents, which is standard PPI. Second, we asked members to participate in voice recorded discussions, contributing to qualitative research data. These discussions revealed different views from those that we heard through research interviews. They allowed us to develop more relevant research tools and resources. Members also helped us to identify people outside the groups who we could interview. Combining involvement and participation helped us to include the views of a wide range of women from 'harder-to-reach' groups who don't usually take part in research. This was important because the research was intended for women who could benefit from incentives to stop smoking in pregnancy and breastfeed, often present in such groups. Positive continuing relationships and trust improved on involvement or participation alone. ᅟ. Patient and public involvement (PPI) in all research studies is recommended from the earliest point and in as many stages as possible. Qualitative research is also recommended in the early stages of designing complex intervention trials. Combining both together might enable inclusion of 'harder-to-reach' perspectives from the target population(s), particularly when the

Preparation and Surface Analysis of PPY/SDBS Films on Aluminum Substrates

Directory of Open Access Journals (Sweden)

Lisete C. Scienza

2001-09-01

Full Text Available Polypyrrole films were generated on high purity aluminum substrates under anodic polarization from aqueous electrolytes comprised of pyrrole and sodium dodecylbenzene sulfonate. The methods employed to characterize the polymer films included scanning electron microscopy, Fourier-transform infrared and X-photoelectron spectroscopy and X-ray diffraction. PPY/SDBS films revealed nodular morphology with occasional appearing of "dendrites", high level of protonation, excess of counter-anions ([S]/[N] > [N+]/[N] and high degrees of disorder.

The α2C-adrenoceptor antagonist, ORM-10921, has antipsychotic-like effects in social isolation reared rats and bolsters the response to haloperidol.

Science.gov (United States)

Uys, Madeleine; Shahid, Mohammed; Sallinen, Jukka; Dreyer, Walter; Cockeran, Marike; Harvey, Brian H

2016-11-03

Early studies suggest that selective α2C-adrenoceptor (AR)-antagonism has anti-psychotic-like and pro-cognitive properties. However, this has not been demonstrated in an animal model of schizophrenia with a neurodevelopmental construct. The beneficial effects of clozapine in refractory schizophrenia and associated cognitive deficits have, among others, been associated with its α2C-AR modulating activity. Altered brain-derived neurotrophic factor (BDNF) has been linked to schizophrenia and cognitive deficits. We investigated whether the α2C-AR antagonist, ORM-10921, could modulate sensorimotor gating and cognitive deficits, as well as alter striatal BDNF levels in the social isolation reared (SIR) model of schizophrenia, comparing its effects to clozapine and the typical antipsychotic, haloperidol, the latter being devoid of α2C-AR-activity. Moreover, the ability of ORM-10921 to augment the effects of haloperidol on the above parameters was also investigated. Animals received subcutaneous injection of either ORM-10921 (0.01mg/kg), clozapine (5mg/kg), haloperidol (0.2mg/kg), haloperidol (0.2mg/kg)+ORM-10921 (0.01mg/kg) or vehicle once daily for 14days, followed by assessment of novel object recognition (NOR), prepulse inhibition (PPI) of startle response and striatal BDNF levels. SIR significantly attenuated NOR memory as well as PPI, and reduced striatal BDNF levels vs. social controls. Clozapine, ORM-10921 and haloperidol+ORM-10921, but not haloperidol alone, significantly improved SIR-associated deficits in PPI and NOR, with ORM-10921 also significantly improving PPI deficits vs. haloperidol-treated SIR animals. Haloperidol+ORM-10921 significantly reversed reduced striatal BDNF levels in SIR rats. α2C-AR-antagonism improves deficits in cognition and sensorimotor gating in a neurodevelopmental animal model of schizophrenia and bolsters the effects of a typical antipsychotic, supporting a therapeutic role for α2C-AR-antagonism in schizophrenia. Copyright �

Dependence of the cutoff in lithium plasma harmonics on the delay between the prepulse and the main pulse

International Nuclear Information System (INIS)

Suzuki, M; Baba, M; Kuroda, H; Ganeev, R A; Bom, L B Elouga; Ozaki, T

2012-01-01

We demonstrated the generation of the 43rd harmonic at the wavelength of 18.49 nm (67 eV photon energy) by using laser-ablation lithium plasma irradiated by a Ti:sapphire laser pulse. We found that for low-Z material, such as lithium, the cutoff energy depends strongly on the delay time between the prepulse and the main pulse, due to rapid recombination. As a result, the maximum cutoff energy was obtained at a relatively short delay of 24 ns. From the theoretical cutoff rule and hydrodynamic simulations, we show that these harmonics were generated from singly charged lithium ions. (paper)

Differences in toxicity of anionic and cationic PAMAM and PPI dendrimers in zebrafish embryos and cancer cell lines

Energy Technology Data Exchange (ETDEWEB)

Bodewein, Lambert [Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine and Pharmacology, Frankfurt & Aachen (Germany); Institute of Environmental Research (Biology V), RWTH Aachen University (Germany); Schmelter, Frank; Di Fiore, Stefano [Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Molecular Biology Division, Aachen (Germany); Hollert, Henner [Institute of Environmental Research (Biology V), RWTH Aachen University (Germany); Fischer, Rainer [Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine and Pharmacology, Frankfurt & Aachen (Germany); Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Molecular Biology Division, Aachen (Germany); Fenske, Martina, E-mail: martina.fenske@ime.fraunhofer.de [Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine and Pharmacology, Frankfurt & Aachen (Germany)

2016-08-15

Dendrimers are an emerging class of polymeric nanoparticles with beneficial biomedical applications like early diagnostics, in vitro gene transfection or controlled drug delivery. However, the potential toxic impact of exposure on human health or the environment is often inadequately defined. Thus, polyamidoamine (PAMAM) dendrimers of generations G3.0, 3.5, 4.0, 4.5 and 5.0 and polypropylenimine (PPI) dendrimers G3.0, 4.0 and 5.0 were tested in zebrafish embryos for 96 h and human cancer cell lines for 24 h, to assess and compare developmental in vivo toxicity with cytotoxicity. The zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time, with EC50 values ranging from 0.16 to just below 1.7 μM at 24 and 48 hpf. The predominant effects were mortality, plus reduced heartbeat and blood circulation for PPI dendrimers. Apoptosis in the embryos increased in line with the general toxicity concentration-dependently. Hatch and dechorionation of the embryos increased the toxicity, suggesting a protective role of the chorion. Lower generation dendrimers were more toxic in the embryos whereas the toxicity in the HepG2 and DU145 cell lines increased with increasing generation of cationic PAMAMs and PPI dendrimers. HepG2 were less sensitive than DU145 cells, with IC50 values ≥ 402 μM (PAMAMs) and ≤ 240 μM (PPIs) for HepG2 and ≤ 13.24 μM (PAMAMs) and ≤ 12.84 μM (PPIs) for DU145. Neither in fish embryos nor cells toxicity thresholds were determinable for anionic PAMAM G3.5 and G4.5. The study demonstrated that the cytotoxicity underestimated the in-vivo toxicity of the dendrimers in the fish embryos. - Highlights: • Zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time. • Zebrafish embryo toxicity of cationic dendrimers did not increase with generation. • Cationic dendrimers induced apoptosis in zebrafish embryos. • Toxicity of cationic dendrimers was lower in HepG2 and DU145 than zebrafish embryos. �

Differences in toxicity of anionic and cationic PAMAM and PPI dendrimers in zebrafish embryos and cancer cell lines

International Nuclear Information System (INIS)

Bodewein, Lambert; Schmelter, Frank; Di Fiore, Stefano; Hollert, Henner; Fischer, Rainer; Fenske, Martina

2016-01-01

Dendrimers are an emerging class of polymeric nanoparticles with beneficial biomedical applications like early diagnostics, in vitro gene transfection or controlled drug delivery. However, the potential toxic impact of exposure on human health or the environment is often inadequately defined. Thus, polyamidoamine (PAMAM) dendrimers of generations G3.0, 3.5, 4.0, 4.5 and 5.0 and polypropylenimine (PPI) dendrimers G3.0, 4.0 and 5.0 were tested in zebrafish embryos for 96 h and human cancer cell lines for 24 h, to assess and compare developmental in vivo toxicity with cytotoxicity. The zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time, with EC50 values ranging from 0.16 to just below 1.7 μM at 24 and 48 hpf. The predominant effects were mortality, plus reduced heartbeat and blood circulation for PPI dendrimers. Apoptosis in the embryos increased in line with the general toxicity concentration-dependently. Hatch and dechorionation of the embryos increased the toxicity, suggesting a protective role of the chorion. Lower generation dendrimers were more toxic in the embryos whereas the toxicity in the HepG2 and DU145 cell lines increased with increasing generation of cationic PAMAMs and PPI dendrimers. HepG2 were less sensitive than DU145 cells, with IC50 values ≥ 402 μM (PAMAMs) and ≤ 240 μM (PPIs) for HepG2 and ≤ 13.24 μM (PAMAMs) and ≤ 12.84 μM (PPIs) for DU145. Neither in fish embryos nor cells toxicity thresholds were determinable for anionic PAMAM G3.5 and G4.5. The study demonstrated that the cytotoxicity underestimated the in-vivo toxicity of the dendrimers in the fish embryos. - Highlights: • Zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time. • Zebrafish embryo toxicity of cationic dendrimers did not increase with generation. • Cationic dendrimers induced apoptosis in zebrafish embryos. • Toxicity of cationic dendrimers was lower in HepG2 and DU145 than zebrafish embryos. �

Developmental vitamin D deficiency alters MK-801-induced behaviours in adult offspring.

Science.gov (United States)

Kesby, James P; O'Loan, Jonathan C; Alexander, Suzanne; Deng, Chao; Huang, Xu-Feng; McGrath, John J; Eyles, Darryl W; Burne, Thomas H J

2012-04-01

Developmental vitamin D (DVD) deficiency is a candidate risk factor for developing schizophrenia in humans. In rodents DVD deficiency induces subtle changes in the way the brain develops. This early developmental insult leads to select behavioural changes in the adult, such as an enhanced response to amphetamine-induced locomotion in female DVD-deficient rats but not in male DVD-deficient rats and an enhanced locomotor response to the N-methyl-D: -aspartate (NMDA) receptor antagonist, MK-801, in male DVD-deficient rats. However, the response to MK-801-induced locomotion in female DVD-deficient rats is unknown. Therefore, the aim of the current study was to further examine this behavioural finding in male and female rats and assess NMDA receptor density. DVD-deficient Sprague Dawley rats were assessed for locomotion, ataxia, acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR to multiple doses of MK-801. The NMDA receptor density in relevant brain regions was assessed in a drug-naive cohort. DVD deficiency increased locomotion in response to MK-801 in both sexes. DVD-deficient rats also showed an enhanced ASR compared with control rats, but PPI was normal. Moreover, DVD deficiency decreased NMDA receptor density in the caudate putamen of both sexes. These results suggest that a transient prenatal vitamin D deficiency has a long-lasting effect on NMDA-mediated signalling in the rodent brain and may be a plausible candidate risk factor for schizophrenia and other neuropsychiatric disorders.

msiDBN: A Method of Identifying Critical Proteins in Dynamic PPI Networks

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Yuan Zhang

2014-01-01

Full Text Available Dynamics of protein-protein interactions (PPIs reveals the recondite principles of biological processes inside a cell. Shown in a wealth of study, just a small group of proteins, rather than the majority, play more essential roles at crucial points of biological processes. This present work focuses on identifying these critical proteins exhibiting dramatic structural changes in dynamic PPI networks. First, a comprehensive way of modeling the dynamic PPIs is presented which simultaneously analyzes the activity of proteins and assembles the dynamic coregulation correlation between proteins at each time point. Second, a novel method is proposed, named msiDBN, which models a common representation of multiple PPI networks using a deep belief network framework and analyzes the reconstruction errors and the variabilities across the time courses in the biological process. Experiments were implemented on data of yeast cell cycles. We evaluated our network construction method by comparing the functional representations of the derived networks with two other traditional construction methods. The ranking results of critical proteins in msiDBN were compared with the results from the baseline methods. The results of comparison showed that msiDBN had better reconstruction rate and identified more proteins of critical value to yeast cell cycle process.

Dielectric and electrical study of PPy doped PVA-PVP films

Science.gov (United States)

Jha, Sushma; Tripathi, Deepti

2018-05-01

Dielectric parameters of free standing films of pure PVA (PolyvinylAlcohol) and PVA with varying concentrations of PVP(Polyvinylpyrrolidone) and Polypyrrole were prepared and studied in low frequency range (100Hz - 2MHz). The results show that dielectric constant, loss tangent and conductivity increase sharply on increasing the concentration of PVP above 50wt% in polymer matrix. PVA-PVP film with low concentration of PPy showed improvement in the values of complex permittivity, loss tangent and ac conductivity within the experimental frequency range. This eco - friendly polymeric material will be studied for its probable application for RFI/EMI shielding, biosensors, capacitors & insulation purposes.

pH-dependent antitumor activity of proton pump inhibitors against human melanoma is mediated by inhibition of tumor acidity.

Science.gov (United States)

De Milito, Angelo; Canese, Rossella; Marino, Maria Lucia; Borghi, Martina; Iero, Manuela; Villa, Antonello; Venturi, Giulietta; Lozupone, Francesco; Iessi, Elisabetta; Logozzi, Mariantonia; Della Mina, Pamela; Santinami, Mario; Rodolfo, Monica; Podo, Franca; Rivoltini, Licia; Fais, Stefano

2010-07-01

Metastatic melanoma is associated with poor prognosis and still limited therapeutic options. An innovative treatment approach for this disease is represented by targeting acidosis, a feature characterizing tumor microenvironment and playing an important role in cancer malignancy. Proton pump inhibitors (PPI), such as esomeprazole (ESOM) are prodrugs functionally activated by acidic environment, fostering pH neutralization by inhibiting proton extrusion. We used human melanoma cell lines and xeno-transplated SCID mice to provide preclinical evidence of ESOM antineoplastic activity. Human melanoma cell lines, characterized by different mutation and signaling profiles, were treated with ESOM in different pH conditions and evaluated for proliferation, viability and cell death. SCID mice engrafted with human melanoma were used to study ESOM administration effects on tumor growth and tumor pH by magnetic resonance spectroscopy (MRS). ESOM inhibited proliferation of melanoma cells in vitro and induced a cytotoxicity strongly boosted by low pH culture conditions. ESOM-induced tumor cell death occurred via rapid intracellular acidification and activation of several caspases. Inhibition of caspases activity by pan-caspase inhibitor z-vad-fmk completely abrogated the ESOM-induced cell death. ESOM administration (2.5 mg kg(-1)) to SCID mice engrafted with human melanoma reduced tumor growth, consistent with decrease of proliferating cells and clear reduction of pH gradients in tumor tissue. Moreover, systemic ESOM administration dramatically increased survival of human melanoma-bearing animals, in absence of any relevant toxicity. These data show preclinical evidence supporting the use of PPI as novel therapeutic strategy for melanoma, providing the proof of concept that PPI target human melanoma modifying tumor pH gradients.

Dual emitter IrQ(ppy)2 for OLED applications: Synthesis and spectroscopic analysis

International Nuclear Information System (INIS)

Ciobotaru, I.C.; Polosan, S.; Ciobotaru, C.C.

2014-01-01

The synthesis of organometallic compound with iridium and two types of ligands, quinoline and phenylpyridine, was done successfully. The absorption spectra of this compound have shown broad peaks in a visible region assigned to metal-to-ligands charge transfer and in UV region assigned to intraligand absorptions. The photoluminescence spectra exhibit dual character in which the red emission is more intense than the green one. In cathodoluminescence measurements, under electron beam, the powder obtained after recrystallization from dichloromethane, shows similar behaviors with photoluminescence spectra. The cathodoluminescence images have shown a luminescent crystalline powder with triclinic structure. This compound exhibits combined vibrational modes, which proves the presence in the same molecule of both ligands. Density Functional Theory calculation was involved in order to identify the main vibrations of this compound. Highlights: • Mixed-ligand of IrQ(ppy) 2 synthesis which gives green and red phosphorescence due to the MCLT processes coming from two types of ligands. • Absorption, photoluminescence, infrared spectroscopy and cathodoluminescence measurements for characterization of IrQ(ppy) 2 organometallic compound. • Experimental results have been compared with the output files obtained from Density Functional Theory by using the Gaussian 03W software

Synthesis and characterization of LDH/Ppi composite and its application as adsorbent of 2,4-dichlorophenoxyacetic (herbicide)

International Nuclear Information System (INIS)

Pacheco, I.S.; Oliveira, R.S.; Girotto, L.G.; Freitas, L.L. de; Amaral, F.A. do; Canobre, S.C.

2016-01-01

This work had as main objective the synthesis and characterization of LDH [Co-Al-Cl] method by hydrolysis of urea and then its synthesized polypyrrole coating by chemically targeting the application as adsorbent dichlorophenoxyacetic acid (2,4-D). The x-ray diffractogram of well defined showed diffraction peaks corresponding to the planes 003, 006, 009 and 110 which allow them to rhombohedral indexes and lamellar structure. The composite LDH / Ppi had a percentage of 49% herbicide retention in aqueous solution. From the investigated adsorption isotherm models that more fit the experimental data was the Freundlich, so it could be inferred that the interaction between the LDH / Ppi and the herbicide was physical, ie an rapid, reversible adsorption and does not specify. (author)

Fe{sub 3}O{sub 4}@SiO{sub 2}–SO{sub 3}H@PPy@Au spheres: Fabrication, characterization and application in SERS

Energy Technology Data Exchange (ETDEWEB)

Ren, Guohong; Shang, Mengying; Zou, Hanzhi; Wang, Wenqin, E-mail: wangwenqin@nbu.edu.cn

2016-04-15

In this work, the sulfonic acid (–SO{sub 3}H) group terminated Fe{sub 3}O{sub 4}@SiO{sub 2} magnetic spheres were prepared. Polypyrrole (PPy) was in-situ polymerized on Fe{sub 3}O{sub 4}@SiO{sub 2}–SO{sub 3}H spheres due to the dual roles of the –SO{sub 3}H groups: acting as both “anchoring sites” for adsorbing of pyrrole monomer and dopant agent in PPy. By adsorbing gold nanoseeds on the as-prepared Fe{sub 3}O{sub 4}@SiO{sub 2}–SO{sub 3}H@PPy spheres followed the seed-mediated growth method, the multifunctional Fe{sub 3}O{sub 4}@SiO{sub 2}–SO{sub 3}H@PPy@Au spheres were obtained. The application of Fe{sub 3}O{sub 4}@SiO{sub 2}–SO{sub 3}H@PPy@Au spheres in surface-enhanced Raman scattering (SERS) was investigated, and the results exhibited the enhancement in the order of 10{sup 4} using 4-aminothiophenol as the probe molecule. - Highlights: • The sulfonic acid-terminated Fe{sub 3}O{sub 4}@SiO{sub 2} (Fe{sub 3}O{sub 4}@SiO{sub 2}–SO{sub 3}H) spheres were prepared. • The –SO{sub 3}H groups of Fe{sub 3}O{sub 4}@SiO{sub 2}–SO{sub 3}H spheres played dual roles in adsorbing pyrrole and protonating polypyrrole. • Fe{sub 3}O{sub 4}@SiO{sub 2}–SO{sub 3}H@PPy core/gold shell composites can act as SERS substrate for detecting 4-ATP molecule.

Potential mechanism of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD.

Science.gov (United States)

Mukaisho, Ken-ichi; Hagiwara, Tadashi; Nakayama, Takahisa; Hattori, Takanori; Sugihara, Hiroyuki

2014-09-14

The long-term use of proton pump inhibitors (PPIs) exacerbates corpus atrophic gastritis in patients with Helicobacter pylori (H. pylori) infection. To identify a potential mechanism for this change, we discuss interactions between pH, bile acids, and H. pylori. Duodenogastric reflux, which includes bile, occurs in healthy individuals, and bile reflux is increased in patients with gastroesophageal reflux disease (GERD). Diluted human plasma and bile acids have been found to be significant chemoattractants and chemorepellents, respectively, for the bacillus H. pylori. Although only taurine conjugates, with a pKa of 1.8-1.9, are soluble in an acidic environment, glycine conjugates, with a pKa of 4.3-5.2, as well as taurine-conjugated bile acids are soluble in the presence of PPI therapy. Thus, the soluble bile acid concentrations in the gastric contents of patients with GERD after continuous PPI therapy are considerably higher than that in those with intact acid production. In the distal stomach, the high concentration of soluble bile acids is likely to act as a bactericide or chemorepellent for H. pylori. In contrast, the mucous layer in the proximal stomach has an optimal bile concentration that forms chemotactic gradients with plasma components required to direct H. pylori to the epithelial surface. H. pylori may then colonize in the stomach body rather than in the pyloric antrum, which may explain the occurrence of corpus-predominant gastritis after PPI therapy in H. pylori-positive patients with GERD.

Studying prepulse inhibition in a stressed system

NARCIS (Netherlands)

Douma, T.N.

2013-01-01

Onset and course of psychotic disorders are thought to be influenced by stress, although there is no consistent evidence that experience of elevated levels of stress triggers disease onset in healthy individuals. In order to better understand the relation between stress and psychosis, these complex

A mouse model of the schizophrenia-associated 1q21.1 microdeletion syndrome exhibits altered mesolimbic dopamine transmission

DEFF Research Database (Denmark)

Nielsen, Jacob; Fejgin, Kim; Sotty, Florence

2017-01-01

on schizophrenia-related assays. Df(h1q21)/+ mice displayed increased hyperactivity in response to amphetamine challenge and increased sensitivity to the disruptive effects of amphetamine and phencyclidine hydrochloride (PCP) on prepulse inhibition. Probing of the direct dopamine (DA) pathway using the DA D1...... and basic functions such as reflexes, ASR, thermal pain sensitivity, and motor performance were unaltered. Similarly, anxiety related measures, baseline prepulse inhibition, and seizure threshold were unaltered. In addition to the central nervous system-related phenotypes, Df(h1q21)/+ mice exhibited reduced...

Changes in cerebro-cerebellar interaction during response inhibition after performance improvement.

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Hirose, Satoshi; Jimura, Koji; Kunimatsu, Akira; Abe, Osamu; Ohtomo, Kuni; Miyashita, Yasushi; Konishi, Seiki

2014-10-01

It has been demonstrated that motor learning is supported by the cerebellum and the cerebro-cerebellar interaction. Response inhibition involves motor responses and the higher-order inhibition that controls the motor responses. In this functional MRI study, we measured the cerebro-cerebellar interaction during response inhibition in two separate days of task performance, and detected the changes in the interaction following performance improvement. Behaviorally, performance improved in the second day, compared to the first day. The psycho-physiological interaction (PPI) analysis revealed the interaction decrease from the right inferior frontal cortex (rIFC) to the cerebellum (lobule VII or VI). It was also revealed that the interaction increased from the same cerebellar region to the primary motor area. These results suggest the involvement of the cerebellum in response inhibition, and raise the possibility that the performance improvement was supported by the changes in the cerebro-cerebellar interaction. Copyright © 2014 Elsevier Inc. All rights reserved.

Influence of Aripiprazole, Risperidone, and Amisulpride on Sensory and Sensorimotor Gating in Healthy ‘Low and High Gating' Humans and Relation to Psychometry

Science.gov (United States)

Csomor, Philipp A; Preller, Katrin H; Geyer, Mark A; Studerus, Erich; Huber, Theodor; Vollenweider, Franz X

2014-01-01

Despite advances in the treatment of schizophrenia spectrum disorders with atypical antipsychotics (AAPs), there is still need for compounds with improved efficacy/side-effect ratios. Evidence from challenge studies suggests that the assessment of gating functions in humans and rodents with naturally low-gating levels might be a useful model to screen for novel compounds with antipsychotic properties. To further evaluate and extend this translational approach, three AAPs were examined. Compounds without antipsychotic properties served as negative control treatments. In a placebo-controlled, within-subject design, healthy males received either single doses of aripiprazole and risperidone (n=28), amisulpride and lorazepam (n=30), or modafinil and valproate (n=30), and placebo. Prepulse inhibiton (PPI) and P50 suppression were assessed. Clinically associated symptoms were evaluated using the SCL-90-R. Aripiprazole, risperidone, and amisulpride increased P50 suppression in low P50 gaters. Lorazepam, modafinil, and valproate did not influence P50 suppression in low gaters. Furthermore, low P50 gaters scored significantly higher on the SCL-90-R than high P50 gaters. Aripiprazole increased PPI in low PPI gaters, whereas modafinil and lorazepam attenuated PPI in both groups. Risperidone, amisulpride, and valproate did not influence PPI. P50 suppression in low gaters appears to be an antipsychotic-sensitive neurophysiologic marker. This conclusion is supported by the association of low P50 suppression and higher clinically associated scores. Furthermore, PPI might be sensitive for atypical mechanisms of antipsychotic medication. The translational model investigating differential effects of AAPs on gating in healthy subjects with naturally low gating can be beneficial for phase II/III development plans by providing additional information for critical decision making. PMID:24801767

Corrosion of conductive polypyrrole: Effects of environmental factors, electrochemical stimulation, and doping anions

International Nuclear Information System (INIS)

Qi Kai; Qiu Yubing; Chen Zhenyu; Guo Xingpeng

2012-01-01

Highlights: ► Corrosive galvanic cells form on PPy film with the electrochemical reduction of O 2. ► Suitable electrochemical stimulation can inhibit the PPy’s corrosion. ► PPy film doped with larger sized anions has better corrosion resistance performance. - Abstract: The effects of environmental factors, electrochemical stimulation, and doping anions on the corrosion behaviour of conductive polypyrrole (PPy) films in alkaline aqueous media were studied with cyclic voltammetry, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. High concentrations of electrolyte, low dissolved oxygen and low temperatures enhance the stability of PPy. Polarising PPy at a negative potential inhibits its corrosion obviously. PPy doped with large counter anions shows better corrosion resistance than PPy doped with small counter ions. The possible mechanism involved in PPy corrosion process is discussed.

Overexpression of Reelin prevents the manifestation of behavioral phenotypes related to schizophrenia and bipolar disorder.

Science.gov (United States)

Teixeira, Cátia M; Martín, Eduardo D; Sahún, Ignasi; Masachs, Nuria; Pujadas, Lluís; Corvelo, André; Bosch, Carles; Rossi, Daniela; Martinez, Albert; Maldonado, Rafael; Dierssen, Mara; Soriano, Eduardo

2011-11-01

Despite the impact of schizophrenia and mood disorders, which in extreme cases can lead to death, recent decades have brought little progress in the development of new treatments. Recent studies have shown that Reelin, an extracellular protein that is critical for neuronal development, is reduced in schizophrenia and bipolar disorder patients. However, data on a causal or protective role of Reelin in psychiatric diseases is scarce. In order to study the direct influence of Reelin's levels on behavior, we subjected two mouse lines, in which Reelin levels are either reduced (Reelin heterozygous mice) or increased (Reelin overexpressing mice), to a battery of behavioral tests: open-field, black-white box, novelty-suppressed-feeding, forced-swim-test, chronic corticosterone treatment followed by forced-swim-test, cocaine sensitization and pre-pulse inhibition (PPI) deficits induced by N-methyl-D-aspartate (NMDA) antagonists. These tests were designed to model some aspects of psychiatric disorders such as schizophrenia, mood, and anxiety disorders. We found no differences between Reeler heterozygous mice and their wild-type littermates. However, Reelin overexpression in the mouse forebrain reduced the time spent floating in the forced-swim-test in mice subjected to chronic corticosterone treatment, reduced behavioral sensitization to cocaine, and reduced PPI deficits induced by a NMDA antagonist. In addition, we demonstrate that while stress increased NMDA NR2B-mediated synaptic transmission, known to be implicated in depression, Reelin overexpression significantly reduced it. Together, these results point to the Reelin signaling pathway as a relevant drug target for the treatment of a range of psychiatric disorders.

Characterization of poly pyrrole/montmorillonite electro polymerised onto Pt; Caracterizacao de filmes PPy/montmorilonita eletropolimerizados sobre Pt

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Castagno, K.R.L., E-mail: katiarlc@pelotas.ifsul.edu.b [Instituto Federal Sul-rio-grandense (IFSul), RS (Brazil). Dept. de Quimica; Azambuja, D.S.; Dalmoro, V.; Mauller, R.S. [Universidade Federal do Rio Grande do Sul (UFRGS), Pelotas, RS (Brazil). Inst. de Quimica

2010-07-01

In this study films of polypyrrole/montmorillonite (PPy/MT) were electropolymerized on platinum in order to evaluate the performance of this technique in the preparation of nanocomposite materials and to determine the thermal properties and conductivity of the composites. The films were synthesized from a solution containing pyrrole, dodecylbenzene sulfonate, acid and two types of clays: montmorillonite-Na + (MT-Na) and montmorillonite-30B (MT-M). The characterization of the films we have used FT-IR, TEM, XRD, TGA, DSC and resistivity measurement by the four-point van der Pauw method. The study showed that the adopted method of exfoliation and the electropolymerization method used, allows obtaining nanocomposite materials. Analyses of FT-IR, TEM and XRD show that the clays are exfoliated in the polymer matrix. Thermal analysis of the films indicates that the addition of clay reflects an enhancement in the thermal properties of the matrix of PPy, but decreases the conductivity of the same. (author)

PPy@MIL-100 Nanoparticles as a pH- and Near-IR-Irradiation-Responsive Drug Carrier for Simultaneous Photothermal Therapy and Chemotherapy of Cancer Cells.

Science.gov (United States)

Zhu, Yu-Da; Chen, Su-Ping; Zhao, Huan; Yang, You; Chen, Xiao-Qin; Sun, Jing; Fan, Hong-Song; Zhang, Xing-Dong

2016-12-21

A medical nanoplatform with small size, low cost, biocompatibility, good biodegradability, and, in particular, multifunctionality has attracted much attention in the exploration of novel therapeutic methodologies. As an emerging material of self-assembled porous structure, metal-organic frameworks (MOFs) have high expectations because of their special properties compared to traditional porous materials. Therefore, integration of MOFs and functional materials is leading to the creation of new multifunctional composites/hybrids. Photothermal therapy (PTT), using near-IR (NIR) laser-absorbing nanomaterials as PTT agents, has shown encouraging therapeutic effects to photothermally ablate tumors. However, the most of widely used PTT agents are inorganic materials and nonbiodegradable. Herein, uniform polypyrrole (PPy) nanoparticles (NPs) with good biodegradability were synthesized by a microemulsion method. The PPy NPs were further coated with the mesoporous iron-based MOF structure MIL-100 by interaction between PPy NPs and MIL-100 precursors at room temperature. As a multifunctional nanoplatform, an anticancer drug could easily be loaded into the mesopores of the MIL-100 shell. The PPy core, as an organic photothermal agent, is able to photothermally ablate cancer cells and improve the efficacy of chemotherapy under NIR irradiation. The composites showed an outstanding in vivo synergistic anticancer capacity. Our work could encourage further study in the construction of a synergetic system using MOFs and organic PTT agents.

Sex-Specific Brain Deficits in Auditory Processing in an Animal Model of Cocaine-Related Schizophrenic Disorders

Directory of Open Access Journals (Sweden)

Patricia A. Broderick

2013-04-01

Full Text Available Cocaine is a psychostimulant in the pharmacological class of drugs called Local Anesthetics. Interestingly, cocaine is the only drug in this class that has a chemical formula comprised of a tropane ring and is, moreover, addictive. The correlation between tropane and addiction is well-studied. Another well-studied correlation is that between psychosis induced by cocaine and that psychosis endogenously present in the schizophrenic patient. Indeed, both of these psychoses exhibit much the same behavioral as well as neurochemical properties across species. Therefore, in order to study the link between schizophrenia and cocaine addiction, we used a behavioral paradigm called Acoustic Startle. We used this acoustic startle paradigm in female versus male Sprague-Dawley animals to discriminate possible sex differences in responses to startle. The startle method operates through auditory pathways in brain via a network of sensorimotor gating processes within auditory cortex, cochlear nuclei, inferior and superior colliculi, pontine reticular nuclei, in addition to mesocorticolimbic brain reward and nigrostriatal motor circuitries. This paper is the first to report sex differences to acoustic stimuli in Sprague-Dawley animals (Rattus norvegicus although such gender responses to acoustic startle have been reported in humans (Swerdlow et al. 1997 [1]. The startle method monitors pre-pulse inhibition (PPI as a measure of the loss of sensorimotor gating in the brain's neuronal auditory network; auditory deficiencies can lead to sensory overload and subsequently cognitive dysfunction. Cocaine addicts and schizophrenic patients as well as cocaine treated animals are reported to exhibit symptoms of defective PPI (Geyer et al., 2001 [2]. Key findings are: (a Cocaine significantly reduced PPI in both sexes. (b Females were significantly more sensitive than males; reduced PPI was greater in females than in males. (c Physiological saline had no effect on startle in

Evaluation of Pax6 mutant rat as a model for autism.

Directory of Open Access Journals (Sweden)

Toshiko Umeda

Full Text Available Autism is a highly variable brain developmental disorder and has a strong genetic basis. Pax6 is a pivotal player in brain development and maintenance. It is expressed in embryonic and adult neural stem cells, in astrocytes in the entire central nervous system, and in neurons in the olfactory bulb, amygdala, thalamus, and cerebellum, functioning in highly context-dependent manners. We have recently reported that Pax6 heterozygous mutant (rSey(2/+ rats with a spontaneous mutation in the Pax6 gene, show impaired prepulse inhibition (PPI. In the present study, we further examined behaviors of rSey(2/+ rats and revealed that they exhibited abnormality in social interaction (more aggression and withdrawal in addition to impairment in rearing activity and in fear-conditioned memory. Ultrasonic vocalization (USV in rSey(2+ rat pups was normal in male but abnormal in female. Moreover, treatment with clozapine successfully recovered the defects in sensorimotor gating function, but not in fear-conditioned memory. Taken together with our prior human genetic data and results in other literatures, rSey(2/+ rats likely have some phenotypic components of autism.

Effects of periadolescent fluoxetine and paroxetine on elevated plus-maze, acoustic startle, and swimming immobility in rats while on and off-drug

Directory of Open Access Journals (Sweden)

Williams Michael T

2011-10-01

Full Text Available Abstract Rationale Whether selective serotonin reuptake inhibitors (SSRIs exposure during adolescent brain development causes lasting effects remains unresolved. Objective Assess the effects of fluoxetine and paroxetine 60 days after adolescent exposure compared with when on-drug. Methods Male Sprague-Dawley littermates (41 litters were gavaged on postnatal days 33-53 with fluoxetine (3 or 10 mg/kg/day, paroxetine (3, 10 or, 17 mg/kg/day, or water; half were tested while on-drug (21 litters and half after 60 days off-drug (20 litters. Results The highest dose of the drugs reduced body weight gain during treatment that rebounded 1 week post-treatment. On-drug, no significant group differences were found on elevated plus maze time-in-open, zone entries, or latency to first open entry; however, the high dose of paroxetine significantly reduced head-dips (N = 20/group. No significant effects were found on-drug for acoustic startle response/prepulse inhibition (ASR/PPI although a trend (p Conclusions The data provide no evidence that fluoxetine or paroxetine have long-term adverse effects on the behaviors measured here after adolescent to young adult exposure.

Δ9-tetrahydrocannabinol (Δ9-THC) administration after neonatal exposure to phencyclidine potentiates schizophrenia-related behavioral phenotypes in mice.

Science.gov (United States)

Rodríguez, Guadalupe; Neugebauer, Nichole M; Yao, Katherine Lan; Meltzer, Herbert Y; Csernansky, John G; Dong, Hongxin

2017-08-01

The clinical onset of schizophrenia often coincides with cannabis use in adolescents and young adults. However, the neurobiological consequences of this co-morbidity are not well understood. In this study, we examined the effects of Δ9-THC exposure during early adulthood on schizophrenia-related behaviors using a developmental mouse model of schizophrenia. Phencyclidine (PCP) or saline was administered once in neonatal mice (at P7; 10mg/kg). In turn, Δ9-THC or saline was administered sub-acutely later in life to cohorts of animals who had received either PCP or saline (P55-80, 5mg/kg). Mice who were administered PCP alone displayed behavioral changes in the Morris water waze (MWM) and pre-pulse inhibition (PPI) task paradigm that were consistent with schizophrenia-related phenotypes, but not in the locomotor activity or novel object recognition (NOR) task paradigms. Mice who were administered PCP and then received Δ9-THC later in life displayed behavioral changes in the locomotor activity paradigm (pschizophrenia-related phenotype, as well as potentiated changes in the NOR (pschizophrenia-related behavioral phenotypes induced by neonatal exposure to PCP in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessment on tracking error performance of Cascade P/PI, NPID and N-Cascade controller for precise positioning of xy table ballscrew drive system

International Nuclear Information System (INIS)

Abdullah, L; Jamaludin, Z; Rafan, N A; Jamaludin, J; Chiew, T H

2013-01-01

At present, positioning plants in machine tools are looking for high degree of accuracy and robustness attributes for the purpose of compensating various disturbance forces. The objective of this paper is to assess the tracking performance of Cascade P/PI, Nonlinear PID (NPID) and Nonlinear cascade (N-Cascade) controller with the existence of disturbance forces in the form of cutting forces. Cutting force characteristics at different cutting parameters; such as spindle speed rotations is analysed using Fast Fourier Transform. The tracking performance of a Nonlinear cascade controller in presence of these cutting forces is compared with NPID controller and Cascade P/PI controller. Robustness of these controllers in compensating different cutting characteristics is compared based on reduction in the amplitudes of cutting force harmonics using Fast Fourier Transform. It is found that the N-cascade controller performs better than both NPID controller and Cascade P/PI controller. The average percentage error reduction between N-cascade controller and Cascade P/PI controller is about 65% whereas the average percentage error reduction between cascade controller and NPID controller is about 82% at spindle speed of 3000 rpm spindle speed rotation. The finalized design of N-cascade controller could be utilized further for machining application such as milling process. The implementation of N-cascade in machine tools applications will increase the quality of the end product and the productivity in industry by saving the machining time. It is suggested that the range of the spindle speed could be made wider to accommodate the needs for high speed machining

Synthesis, characterization, and applications of electroactive polymeric nanostructures for organic coatings

Science.gov (United States)

Suryawanshi, Abhijit Jagnnath

Electroactive polymers (EAP) such as polypyrrole (PPy) and polyaniline (PANI) are being explored intensively in the scientific community. Nanostructures of EAPs have low dimensions and high surface area enabling them to be considered for various useful applications. These applications are in several fields including corrosion inhibition, capacitors, artificial muscles, solar cells, polymer light emitting diodes, and energy storage devices. Nanostructures of EAPs have been synthesized in different morphologies such as nanowires, nanorods, nanotubes, nanospheres, and nanocapsules. This variety in morphology is traditionally achieved using soft templates, such as surfactant micelles, or hard templates, such as anodized aluminum oxide (AAO). Templates provide stability and groundwork from which the polymer can grow, but the templates add undesirable expense to the process and can change the properties of the nanoparticles by integrating its own properties. In this study a template free method is introduced to synthesize EAP nanostructures of PPy and PANI utilizing ozone oxidation. The simple techniques involve ozone exposure to the monomer solution to produce aqueous dispersions of EAP nanostructures. The synthesized nanostructures exhibit uniform morphology, low particle size distribution, and stability against agglomeration. Ozone oxidation is further explored for the synthesis of silver-PPy (Ag-PPy) core-shell nanospheres (CSNs). Coatings containing PPy nanospheres were formulated to study the corrosion inhibition efficiency of PPy nanospheres. Investigation of the coatings using electrochemical techniques revealed that the PPy nanospheres may provide corrosion inhibition against filiform corrosion by oxygen scavenging mechanism. Finally, organic corrosion inhibitors were incorporated in PPy to develop efficient corrosion inhibiting systems, by using the synergistic effects from PPy and organic corrosion inhibitors.

PPY-PVA Blend Thin Films as a Ammines Gas Sensor

Directory of Open Access Journals (Sweden)

D. B. DUPARE

2009-06-01

Full Text Available Synthesis of polypyrrole–polyvinyl alcohol blend thin by in situ chemical oxidative polymerization, on glass substrate for development of Ammonia and Trimethyl ammine hazardous gas sensor. The all experimental process carried out at room temperature (304 k. These polymer materials were characterized by Chemical analyses, spectral studies (UV-visible and IR and conductivity measurement by four –probe technique. The surface morphology as seen in the SEM image was observed to be granular, tubular, uniformly covering the entire substrate surface having porous in nature. The current–voltage characterization show that these thin films have conducting in nature having ohmic behaviors. The sensor was used for different concentration (ppm of TMA and Ammonia gas investigation at room temperature (304 k. This study found to possess improved electrical, mechanical and environmental stability PPY-PVA films.

Metal Oxides Doped PPY-PVA Blend Thin Films Based Gas Sensor

Directory of Open Access Journals (Sweden)

D. B. DUPARE

2009-02-01

Full Text Available Synthesis of metal oxides doped polypyrrole–polyvinyl alcohol blend thin films by in situ chemical oxidative polymerization, using microwave oven on glass substrate for development of Ammonia and Trimethyl ammine hazardous gas sensor. The all experimental process carried out at room temperature(304 K. These polymer materials were characterized by Chemical analyses, spectral studies (UV-visible and IR and conductivity measurement by four –probe technique. The surface morphology as observed in the SEM image was observed to be uniformly covering the entire substrate surface. The sensor was used for different concentration (ppm of TMA and Ammonia gas investigation at room temperature (304 k. This study found to possess improved electrical, mechanical and environmental stability metal oxides doped PPY-PVA films.

Proton pump inhibitors induce apoptosis of human B-cell tumors through a caspase-independent mechanism involving reactive oxygen species.

Science.gov (United States)

De Milito, Angelo; Iessi, Elisabetta; Logozzi, Mariantonia; Lozupone, Francesco; Spada, Massimo; Marino, Maria Lucia; Federici, Cristina; Perdicchio, Maurizio; Matarrese, Paola; Lugini, Luana; Nilsson, Anna; Fais, Stefano

2007-06-01

Proton pumps like the vacuolar-type H+ ATPase (V-ATPase) are involved in the control of cellular pH in normal and tumor cells. Treatment with proton pump inhibitors (PPI) induces sensitization of cancer cells to chemotherapeutics via modifications of cellular pH gradients. It is also known that low pH is the most suitable condition for a full PPI activation. Here, we tested whether PPI treatment in unbuffered culture conditions could affect survival and proliferation of human B-cell tumors. First, we showed that PPI treatment increased the sensitivity to vinblastine of a pre-B acute lymphoblastic leukemia (ALL) cell line. PPI, per se, induced a dose-dependent inhibition of proliferation of tumor B cells, which was associated with a dose- and time-dependent apoptotic-like cytotoxicity in B-cell lines and leukemic cells from patients with pre-B ALL. The effect of PPI was mediated by a very early production of reactive oxygen species (ROS), that preceded alkalinization of lysosomal pH, lysosomal membrane permeabilization, and cytosol acidification, suggesting an early destabilization of the acidic vesicular compartment. Lysosomal alterations were followed by mitochondrial membrane depolarization, release of cytochrome c, chromatin condensation, and caspase activation. However, inhibition of caspase activity did not affect PPI-induced cell death, whereas specific inhibition of ROS by an antioxidant (N-acetylcysteine) significantly delayed cell death and protected both lysosomal and mitochondrial membranes. The proapoptotic activity of PPI was consistent with a clear inhibition of tumor growth following PPI treatment of B-cell lymphoma in severe combined immunodeficient mice. This study further supports the importance of acidity and pH gradients in tumor cell homeostasis and suggests new therapeutic approaches for human B-cell tumors based on PPI.

PPI therapy is equally effective in well-defined non-erosive reflux disease and in reflux esophagitis: a meta-analysis

NARCIS (Netherlands)

Weijenborg, P. W.; Cremonini, F.; Smout, A. J. P. M.; Bredenoord, A. J.

2012-01-01

Background Symptomatic response to proton pump inhibitor (PPI) therapy in patients with non-erosive reflux disease (NERD) is often reported as lower than in patients with erosive reflux disease (ERD). However, the definition of NERD differs across clinical trials. This meta-analysis aims to estimate

Meta-analyses: does long-term PPI use increase the risk of gastric premalignant lesions?

Science.gov (United States)

Eslami, Layli; Nasseri-Moghaddam, Siavosh

2013-08-01

Proton pump inhibitors (PPIs) are the most effective agents available for reducing acid secretion. They are used for medical treatment of various acid-related disorders. PPIs are used extensively and for extended periods of time in gastroesophageal reflux disease (GERD). A troublesome issue regarding maintenance therapy has been the propensity of PPI-treated patients to develop chronic atrophic gastritis while on therapy that could theoretically lead to an increased incidence of gastric cancer. In addition, animal studies have raised concern for development of enterochromaffin-like cell hyperplasia and carcinoid tumors in the stomachs of mice receiving high dose PPIs. Current literature does not provide a clear-cut conclusion on the subject and the reports are sometimes contradictory. Therefore, this study is a systematic review of the available literature to address the safety of long-term PPI use and its relation to the development of malignant/premalignant gastric lesions. A literature search of biomedical databases was performed. The reference lists of retrieved articles were reviewed to further identify relevant trials. We hand-searched the abstracts of the American Digestive Disease Week (DDW) and the United European Gastroenterology Week (UEGW) from 1995 to 2013. Only randomized clinical trials (RCTs) that used PPIs as the primary treatment for at least six month versus no treatment, placebo, antacid or anti-reflux surgery (ARS) were included. Two reviewers independently extracted the data. Discrepancies in the interpretation were resolved by consensus. All analyses of outcomes were based on the intention-to-treat principle. We performed statistical analysis using Review Manager software. The effect measure of choice was relative risk (RR) for dichotomous data. Six RCTs with a total of 785 patients met the inclusion criteria. Two multicenter RCTs compared Esomeprazole with placebo. One RCT compared omeprazole with ARS. Two RCTs compared omeprazole with

In vitro and in vivo plasmalogen replacement evaluations in rhizomelic chrondrodysplasia punctata and Pelizaeus-Merzbacher disease using PPI-1011, an ether lipid plasmalogen precursor

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Wood Paul L

2011-10-01

Full Text Available Abstract Background Childhood peroxisomal disorders and leukodystrophies are devastating diseases characterized by dysfunctional lipid metabolism. Plasmalogens (ether glycerophosphoethanolamine lipids are decreased in these genetic disorders. The biosynthesis of plasmalogens is initiated in peroxisomes but completed in the endoplasmic reticulum. We therefore undertook a study to evaluate the ability of a 3-substituted, 1-alkyl, 2-acyl glyceryl ether lipid (PPI-1011 to replace plasmalogens in rhizomelic chrondrodysplasia punctata type 1 (RCDP1 and rhizomelic chrondrodysplasia punctata type 2 (RCDP2 lymphocytes which possess peroxisomal mutations culminating in deficient plasmalogen synthesis. We also examined plasmalogen synthesis in Pelizaeus-Merzbacher disease (PMD lymphocytes which possess a proteolipid protein-1 (PLP1 missense mutation that results in abnormal PLP1 folding and it's accumulation in the endoplasmic reticulum (ER, the cellular site of the last steps in plasmalogen synthesis. In vivo incorporation of plasmalogen precursor into tissue plasmalogens was also evaluated in the Pex7 mouse model of plasmalogen deficiency. Results In both RCDP1 and RCDP2 lymphocytes, PPI-1011 repleted the target ethanolamine plasmalogen (PlsEtn16:0/22:6 in a concentration dependent manner. In addition, deacylation/reacylation reactions resulted in repletion of PlsEtn 16:0/20:4 in both RCDP1 and RCDP2 lymphocytes, repletion of PlsEtn 16:0/18:1 and PlsEtn 16:0/18:2 in RCDP2 lymphocytes, and partial repletion of PlsEtn 16:0/18:1 and PlsEtn 16:0/18:2 in RCDP1 lymphocytes. In the Pex7 mouse, oral dosing of labeled PPI-1011 demonstrated repletion of tissue levels of the target plasmalogen PlsEtn 16:0/22:6 with phospholipid remodeling also resulting in significant repletion of PlsEtn 16:0/20:4 and PlsEtn 16:0/18:1. Metabolic conversion of PPI-1011 to the target plasmalogen was most active in the liver. Conclusions Our data demonstrate that PPI-1011 is activated

Meis1: effects on motor phenotypes and the sensorimotor system in mice

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Aaro V. Salminen

2017-08-01

Full Text Available MEIS1 encodes a developmental transcription factor and has been linked to restless legs syndrome (RLS in genome-wide association studies. RLS is a movement disorder leading to severe sleep reduction and has a substantial impact on the quality of life of patients. In genome-wide association studies, MEIS1 has consistently been the gene with the highest effect size and functional studies suggest a disease-relevant downregulation. Therefore, haploinsufficiency of Meis1 could be the system with the most potential for modeling RLS in animals. We used heterozygous Meis1-knockout mice to study the effects of Meis1 haploinsufficiency on mouse behavioral and neurological phenotypes, and to relate the findings to human RLS. We exposed the Meis1-deficient mice to assays of motor, sensorimotor and cognitive ability, and assessed the effect of a dopaminergic receptor 2/3 agonist commonly used in the treatment of RLS. The mutant mice showed a pattern of circadian hyperactivity, which is compatible with human RLS. Moreover, we discovered a replicable prepulse inhibition (PPI deficit in the Meis1-deficient animals. In addition, these mice were hyposensitive to the PPI-reducing effect of the dopaminergic receptor agonist, highlighting a role of Meis1 in the dopaminergic system. Other reported phenotypes include enhanced social recognition at an older age that was not related to alterations in adult olfactory bulb neurogenesis previously shown to be implicated in this behavior. In conclusion, the Meis1-deficient mice fulfill some of the hallmarks of an RLS animal model, and revealed the role of Meis1 in sensorimotor gating and in the dopaminergic systems modulating it.

Effects of periadolescent fluoxetine and paroxetine on elevated plus-maze, acoustic startle, and swimming immobility in rats while on and off-drug.

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Vorhees, Charles V; Morford, LaRonda R; Graham, Devon L; Skelton, Matthew R; Williams, Michael T

2011-10-05

Whether selective serotonin reuptake inhibitors (SSRIs) exposure during adolescent brain development causes lasting effects remains unresolved. Assess the effects of fluoxetine and paroxetine 60 days after adolescent exposure compared with when on-drug. Male Sprague-Dawley littermates (41 litters) were gavaged on postnatal days 33-53 with fluoxetine (3 or 10 mg/kg/day), paroxetine (3, 10 or, 17 mg/kg/day), or water; half were tested while on-drug (21 litters) and half after 60 days off-drug (20 litters). The highest dose of the drugs reduced body weight gain during treatment that rebounded 1 week post-treatment. On-drug, no significant group differences were found on elevated plus maze time-in-open, zone entries, or latency to first open entry; however, the high dose of paroxetine significantly reduced head-dips (N=20/group). No significant effects were found on-drug for acoustic startle response/prepulse inhibition (ASR/PPI) although a trend (pfluoxetine and paroxetine (N=20-21/group). No differences on immobility time were seen in the Porsolt forced swim test or in plasma corticosterone at the end of forced swim (N-19-21/group). Off-drug, no effects were seen in the elevated plus maze (N=16/group), ASR/PPI (N=20/group), forced swim (N=19-20/group), or plasma corticosterone (N=19/group). At the doses tested, fluoxetine and paroxetine induced minor effects with drug on-board but no residual, long-term adverse effects in rats 60 days after drug discontinuation. The data provide no evidence that fluoxetine or paroxetine have long-term adverse effects on the behaviors measured here after adolescent to young adult exposure.

Investigating the Role of Serotonin in Methamphetamine Psychosis: Unaltered Behavioral Effects of Chronic Methamphetamine in 5-HT1A Knockout Mice

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Maarten van den Buuse

2017-04-01

Full Text Available Methamphetamine (Meth is a widely abused stimulant drug, but this abuse is associated with an increased risk of developing psychosis. In addition to its well-known action on brain dopamine, Meth also affects serotonergic (5-HT neurons. The aim of this study was to investigate this role in mice, which lack one of the main serotonin receptors, the 5-HT1A receptor, which has been implicated in both schizophrenia and Meth-induced psychosis. Male and female wild-type or 5-HT1A knockout (KO mice received daily treatment with increasing doses of methamphetamine from 6 to 9 weeks of age (1–4 mg/kg/day twice a day. At least 2 weeks after the last injection, the mice underwent a battery of behavioral tests focusing on psychosis-related behaviors, including Meth-induced hyperactivity, prepulse inhibition (PPI, social interaction, elevated plus maze (EPM, and Y-maze. Meth pretreatment resulted in significantly increased hyperlocomotion in response to an acute Meth challenge, but this effect was independent of genotype. Chronic Meth treatment resulted in decreased levels of anxiety in the EPM in both sexes, as well as increased startle responses in female mice only, again independent of genotype. 5-HT1A KO mice showed an increased locomotor response to acute Meth in both sexes, as well as increased PPI and decreased startle responses in female mice only, independent of Meth pretreatment. In conclusion, the effects of chronic Meth appear unaffected by the absence of the 5-HT1A receptor. These results do not support a role of the 5-HT1A receptor in Meth-induced psychosis.

Environmental Enrichment Ameliorates Behavioral Impairments Modeling Schizophrenia in Mice Lacking Metabotropic Glutamate Receptor 5.

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Burrows, Emma L; McOmish, Caitlin E; Buret, Laetitia S; Van den Buuse, Maarten; Hannan, Anthony J

2015-07-01

Schizophrenia arises from a complex interplay between genetic and environmental factors. Abnormalities in glutamatergic signaling have been proposed to underlie the emergence of symptoms, in light of various lines of evidence, including the psychotomimetic effects of NMDA receptor antagonists. Metabotropic glutamate receptor 5 (mGlu5) has also been implicated in the disorder, and has been shown to physically interact with NMDA receptors. To clarify the role of mGlu5-dependent behavioral expression by environmental factors, we assessed mGlu5 knockout (KO) mice after exposure to environmental enrichment (EE) or reared under standard conditions. The mGlu5 KO mice showed reduced prepulse inhibition (PPI), long-term memory deficits, and spontaneous locomotor hyperactivity, which were all attenuated by EE. Examining the cellular impact of genetic and environmental manipulation, we show that EE significantly increased pyramidal cell dendritic branching and BDNF protein levels in the hippocampus of wild-type mice; however, mGlu5 KO mice were resistant to these alterations, suggesting that mGlu5 is critical to these responses. A selective effect of EE on the behavioral response to the NMDA receptor antagonist MK-801 in mGlu5 KO mice was seen. MK-801-induced hyperlocomotion was further potentiated in enriched mGlu5 KO mice and treatment with MK-801 reinstated PPI disruption in EE mGlu5 KO mice only, a response that is absent under standard housing conditions. Together, these results demonstrate an important role for mGlu5 in environmental modulation of schizophrenia-related behavioral impairments. Furthermore, this role of the mGlu5 receptor is mediated by interaction with NMDA receptor function, which may inform development of novel therapeutics.

Measurement of the asymmetry parameter for the decay $\\bar\\Lambda \\to \\bar p\\pi^+$

OpenAIRE

BES collaboration

2009-01-01

Based on a sample of $58\\times10^6J/\\psi$ decays collected with the BESII detector at the BEPC, the $\\bar\\Lambda$ decay parameter $\\alpha_{\\bar\\Lambda}$ for $\\bar\\Lambda\\to \\bar p \\pi^+$ is measured using about 9000 $J/\\psi\\to\\Lambda\\bar\\Lambda\\to p \\bar p \\pi^+\\pi^-$ decays. A fit to the joint angular distributions yields $\\alpha_{\\bar\\Lambda}(\\bar\\Lambda\\to \\bar p\\pi^+)=-0.755\\pm0.083\\pm0.063$, where the first error is statistical, and the second systematic.

Status of PPI (Pohang Photo-Injector) for PAL XFEL

CERN Document Server

Park, Sung-Ju; Oh, Jong-Seok; Park, Chong-Do; Park Jang Ho; Soo Ko In; Wang, Xijie; Woon Parc, Yong

2005-01-01

A X-Ray Free Electron Laser (XFEL) project based on the Self-Amplified Spontaneous Emission (SASE) is under progress at the Pohang Accelerator Laboratory (PAL). One of the critical R&D for the PAL XFEL* is to develop the Pohang Photo-Injector (PPI) which is required to deliver electron beams with normalized emittance < 1.5 mm-mrad. In order to achieve the required beam quality with high stability and reliability, we will use photocathode with quantum efficiency > 0.1 % and long lifetime. This will greatly lessen the laser energy requirement for producing flat-top UV pulses, and open the possibility of using only regenerative amplifiers (RGAs) to drive the photocathode RF gun. The RGAs can produce mJs output with much better stability than multi-pass amplifiers. Both the Cs2Te and Mg are under consideration for the possible photo-cathode. To demonstrate the suitability of the Mg and Cs2Te for the future 4th generation light source application, an improved BNL-type S-band RF gun with a high-pe...

A novel EIS field effect structures coated with TESUD-PPy-PVC-dibromoaza[7]helicene matrix for potassium ions detection

Energy Technology Data Exchange (ETDEWEB)

Tounsi, Moncef, E-mail: tounsi1981@live.fr [Laboratoire des Interfaces et des Matériaux Avancés (LIMA), Faculté des Sciences de Monastir, Université de Monastir (Tunisia); Université de Lyon, Institut de Sciences Analytiques (ISA) – UMR 5280, 5 rue de la Doua, 69100 Villeurbanne (France); Ben Braiek, Mourad [Laboratoire de Synthèse Organique Asymétrique et Catalyse Homogène, Faculté des Sciences, Université de Monastir, Avenue de l' environnement, 5019, Monastir (Tunisia); Barhoumi, Houcine [Laboratoire des Interfaces et des Matériaux Avancés (LIMA), Faculté des Sciences de Monastir, Université de Monastir (Tunisia); Baraket, Abdoullatif; Lee, Michael; Zine, Nadia [Université de Lyon, Institut de Sciences Analytiques (ISA) – UMR 5280, 5 rue de la Doua, 69100 Villeurbanne (France); Maaref, Abderrazak [Laboratoire des Interfaces et des Matériaux Avancés (LIMA), Faculté des Sciences de Monastir, Université de Monastir (Tunisia); Errachid, Abdelhamid, E-mail: abdelhamid.errachid-el-salhi@univ-lyon1.fr [Université de Lyon, Institut de Sciences Analytiques (ISA) – UMR 5280, 5 rue de la Doua, 69100 Villeurbanne (France)

2016-04-01

In this work, we describe the development of new Aza[7]helicene-containing PVC-based membranes for the K{sup +} ions quantification. Here, silicon nitride-based structures (Si-p/SiO{sub 2}/Si{sub 3}N{sub 4}) were developed and the surface was activated, functionalized with an aldehyde–silane (11-(Triethoxysilyl)undecanal (TESUD)), functionalized with polypyrrole (PPy), and coated with the polyvinylchloride (PVC)-membrane containing the Aza[7]helicene as ionophore. All stages of functionalization process have been thoroughly studied by contact angle measurements (CAMs) and atomic force microscopy (AFM). The developed ion-selective electrode (ISE) was then applied using electrochemical impedance spectroscopy (EIS) for the detection of potassium ions. A linear range was observed between 1.0 × 10{sup −8} M to 1.0 × 10{sup −3} M and a detection limit of 1.0 × 10{sup −8} M was observed. The EIS results have showed a good sensitivity to potassium ion using this novel technique. The target helicene exhibited good solubility and excellent thermal stability with a high decomposition temperature (Td > 300 °C) and it indicates that helicene may be a promising material as ionophore for ion-selective electrodes (ISEs) elaboration. - Highlights: • Synthesis and characterization of a new derivatives of Aza[7]helicenes • Manufacture of PPy structures on the SiO{sub 2}/Si{sub 3}N{sub 4} surface using the TESUD as cross linking agent. • The PPy fabricated microstructures can be used as support matrix in biosensing. • Impedimetric K{sup +}-ISEs was developed by using dibromoaza[7]helicene as ionophore for K{sup +} ions determination.

Inhibitor candidates's identification of HCV's RNA polymerase NS5B using virtual screening against iPPI-library

Science.gov (United States)

Sulistyawati, Indah; Sulistyo Dwi K., P.; Ichsan, Mochammad

2016-03-01

Hepatitis C is one of the major causes of chronic liver failure that caused by Hepatitis C Virus (HCV). Preventing the progression of HCV's replication through the inhibition of The RNA polymerase NS5B of Hepatitis C virus (NS5B) can be achieved via 4 binding regions: Site I (Thumb I), Site II (Thumb II), Site III (Palm I), and Site IV (Palm II). The aim of this research is to identify a candidate of NS5B inhibitor as an alternative for Hepatitis C treatment. An NS5B's 3D structure (PDB ID = 3D5M) used in this study has met some criteria of a good model to be used in virtual screening againts iPPI-lib using MTiOpenScreen webserver. The top two natural compounds resulted here then docked using Pyrix 0.8 and discovered trans-6-Benzamido-2-methyldecahydroisoquinoline (-9,1kcal/mol) and 2,4-dichloro-5-[4-(2 methoxyphenyl) piperazine-1-carbonyl]-N-[3-(trifluoromethyl)phenyl] benzenesulfonamide (9,4 kcal/mol) can bind to Tyr448 similar with all three established inhibitors, such as setrobuvir (-11,4 kcal/mol; site 3 inhibitor), CHEMBL379677 (-9,1 kcal/mol; site 1 inhibitor), and nesbuvir (-7,7 kcal/mol; site 4 inhibitor). The results of this study are relatively still needs to be tested, both in vitro and in vivo, in order to obtain more comprehensive knowledges as a follow-up of this predictive study.

Neomycin inhibits PDGF-induced IP3 formation and DNA synthesis but not PDGF-stimulated uptake of inorganic phosphate in C3H/10T1/2 fibroblasts.

Science.gov (United States)

Vassbotn, F S; Langeland, N; Holmsen, H

1990-09-01

Porcine PDGF was found to increase [3H]inositol trisphosphate, [3H]thymidine incorporation and 32P-labelling of polyphosphoinositides in C3H/10T1/2 Cl 8 fibroblasts. These responses to PDGF stimulation were all inhibited by 5 mM neomycin, a polycationic aminoglycoside formerly known to inhibit polyphosphoinositide turnover. PDGF also markedly increased the cellular uptake of inorganic [32P]Pi. This response of PDGF was not inhibited by neomycin (5 mM). Thus, neomycin inhibited PDGF-induced IP3 formation, 32P-labelling of polyphosphoinositides and DNA synthesis, but not cellular uptake of inorganic phosphate. These effects of neomycin suggest a bifurcation of the initial part of the PDGF-induced signal transduction, separating at the receptor level or before phospholipase C activation.

Mephedrone (4-Methylmethcathinone: Acute Behavioral Effects, Hyperthermic, and Pharmacokinetic Profile in Rats

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Klára Šíchová

2018-01-01

Full Text Available Mephedrone (MEPH is a synthetic cathinone derivative with effects that mimic MDMA and/or cocaine. Our study in male Wistar rats provides detailed investigations of MEPH’s and its primary metabolite nor-mephedrone’s (nor-MEPH pharmacokinetics and bio-distribution to four different substrates (serum, brain, lungs, and liver, as well as comparative analysis of their effects on locomotion [open field test (OFT] and sensorimotor gating [prepulse inhibition of acoustic startle reaction (PPI ASR]. Furthermore, in order to mimic the crowded condition where MEPH is typically taken (e.g., clubs, the acute effect of MEPH on thermoregulation in singly- and group-housed rats was evaluated. Pharmacokinetics of MEPH and nor-MEPH after MEPH (5 mg/kg, sc. were analyzed over 8 h using liquid chromatography with mass spectrometry. MEPH (2.5, 5, or 20 mg/kg, sc. and nor-MEPH (5 mg/kg, sc. were administered 5 or 40 min before the behavioral testing in the OFT and PPI ASR; locomotion and its spatial distribution, ASR, habituation and PPI itself were quantified. The effect of MEPH on rectal temperature was measured after 5 and 20 mg/kg, sc. Both MEPH and nor-MEPH were detected in all substrates, with the highest levels detected in lungs. Mean brain: serum ratios were 1:1.19 (MEPH and 1:1.91 (nor-MEPH, maximum concentrations were observed at 30 min; at 2 and 4 h after administration, nor-MEPH concentrations were higher compared to the parent drug. While neither of the drugs disrupted PPI, both increased locomotion and affected its spatial distribution. The effects of MEPH were dose dependent, rapid, and short-lasting, and the intensity of locomotor stimulant effects was comparable between MEPH and nor-MEPH. Despite the disappearance of behavioral effects within 40 min after administration, MEPH induced rectal temperature elevations that persisted for 3 h even in singly housed rats. To conclude, we observed a robust, short-lasting, and most

Rapid efflux of Ca2+ from heart mitochondria in the presence of inorganic pyrophosphate.

Science.gov (United States)

Vercesi, A; Lehninger, A L

1984-01-13

Inorganic pyrophosphate (PPi) in the intracellular concentration range causes rapid efflux of Ca2+ from rat heart mitochondria oxidizing pyruvate + malate in a low Na+ medium. Half-maximal rates of Ca2+ efflux were given by 20 microM PPi. During and after PPi-stimulated Ca2+ efflux the mitochondria retain their structural integrity and complete respiratory control. Carboxyatractyloside inhibits PPi-stimulated Ca2+ efflux, indicating PPi must enter the matrix in order to promote Ca2+ efflux. Heart mitochondria have a much higher affinity for PPi uptake and PPi-induced Ca2+ efflux than liver mitochondria.

Lansoprazole induces apoptosis of breast cancer cells through inhibition of intracellular proton extrusion

Energy Technology Data Exchange (ETDEWEB)

Zhang, Shangrong; Wang, Yifan; Li, Shu Jie, E-mail: shujieli@nankai.edu.cn

2014-06-13

Highlights: • Lansoprazole (LPZ) induces cell apoptosis in breast cancer cells. • LPZ markedly inhibits intracellular proton extrusion. • LPZ induces an increase in intracellular ATP level, lysosomal alkalinization and ROS accumulation. - Abstract: The increased glycolysis and proton secretion in tumors is proposed to contribute to the proliferation and invasion of cancer cells during the process of tumorigenesis and metastasis. Here, treatment of human breast cancer cells with proton pump inhibitor (PPI) lansoprazole (LPZ) induces cell apoptosis in a dose-dependent manner. In the implantation of the MDA-MB-231 xenografts in nude mice, administration of LPZ significantly inhibits tumorigenesis and induces large-scale apopotosis of tumor cells. LPZ markedly inhibits intracellular proton extrusion, induces an increase in intracellular ATP level, lysosomal alkalinization and accumulation of reactive oxygen species (ROS) in breast cancer cells. The ROS scavenger N-acetyl-L-cysteine (NAC) and diphenyleneiodonium (DPI), a specific pharmacological inhibitor of NADPH oxidases (NOX), significantly abolish LPZ-induced ROS accumulation in breast cancer cells. Our results suggested that LPZ may be used as a new therapeutic drug for breast tumor.

Lansoprazole induces apoptosis of breast cancer cells through inhibition of intracellular proton extrusion

International Nuclear Information System (INIS)

Zhang, Shangrong; Wang, Yifan; Li, Shu Jie

2014-01-01

Highlights: • Lansoprazole (LPZ) induces cell apoptosis in breast cancer cells. • LPZ markedly inhibits intracellular proton extrusion. • LPZ induces an increase in intracellular ATP level, lysosomal alkalinization and ROS accumulation. - Abstract: The increased glycolysis and proton secretion in tumors is proposed to contribute to the proliferation and invasion of cancer cells during the process of tumorigenesis and metastasis. Here, treatment of human breast cancer cells with proton pump inhibitor (PPI) lansoprazole (LPZ) induces cell apoptosis in a dose-dependent manner. In the implantation of the MDA-MB-231 xenografts in nude mice, administration of LPZ significantly inhibits tumorigenesis and induces large-scale apopotosis of tumor cells. LPZ markedly inhibits intracellular proton extrusion, induces an increase in intracellular ATP level, lysosomal alkalinization and accumulation of reactive oxygen species (ROS) in breast cancer cells. The ROS scavenger N-acetyl-L-cysteine (NAC) and diphenyleneiodonium (DPI), a specific pharmacological inhibitor of NADPH oxidases (NOX), significantly abolish LPZ-induced ROS accumulation in breast cancer cells. Our results suggested that LPZ may be used as a new therapeutic drug for breast tumor

A cog in cognition: how the alpha 7 nicotinic acetylcholine receptor is geared towards improving cognitive deficits.

Science.gov (United States)

Leiser, Steven C; Bowlby, Mark R; Comery, Thomas A; Dunlop, John

2009-06-01

Cognition, memory, and attention and arousal have been linked to nicotinic acetylcholine receptors (nAChRs). Thus it is not surprising that nAChRs have been strongly implicated as therapeutic targets for treating cognitive deficits in disorders such as schizophrenia and Alzheimer's disease (AD). In particular the alpha7 (alpha7) nAChR has been closely linked with normalization of P50 auditory evoked potential (AEP) gating deficits, and to a lesser extent improvements in pre-pulse inhibition (PPI) of the acoustic startle response. These two brain phenomena can be considered as pre-attentive, occurring while sensory information is being processed, and are important endophenotypes in schizophrenia with deficits likely contributing to the cognitive fragmentation associated with the disease. In addition alpha7 nAChRs have been implicated in attention, in particular under high attentional demand, and in more demanding working memory tasks such as long delays in delayed matching tasks. Efficacy of alpha7 nAChR agonists across a range of cognitive processes ranging from pre-attentive to attentive states and working and recognition memory provides a solid basis for their pro-cognitive effects. This review will focus on the recent work highlighting the role of alpha7 in cognition and cognitive processes.

Rapid high resolution MR neurography with a diffusion-weighted pre-pulse

International Nuclear Information System (INIS)

Yoneyama, Masami; Nakamura, Masanobu; Tabuchi, Takashi; Takahara, Taro; Kwee, T.C.

2013-01-01

The purpose of this study was to introduce, optimize, and assess the feasibility of a new scheme to rapidly acquire high-resolution volumetric neurographic images using a three-dimensional turbo spin-echo sequence combined with a diffusion-weighted pre-pulse called improved motion-sensitized driven equilibrium (iMSDE): Diffusion-prepared magnetic resonance (MR) Neurography (D-prep MRN). In order to optimize the signal suppression of blood vessels and muscle at D-prep MRN, coronal lumbosacral plexus images were acquired in five volunteers at 3T, and the following parameters were examined: iMSDE gradient-strength (b-value) of 0, 2 and 10 s/mm 2 (with the aim to suppress blood vessels) and iMSDE preparation duration (iMSDE prep-time ) of 18, 50 and 100 ms (with the aim to suppress muscle signal). Subsequently, the feasibility of the optimized D-prep MRN sequence in visualizing the brachial plexus, lumbosacral plexus, and cranial nerves was evaluated in 5 healthy volunteers. A higher b-value of 10 s/mm 2 was better in signal suppression of blood vessels, whereas an intermediate iMSDE prep-time of 50 ms provided the best compromise between suppression of muscle signal and minimization of signal loss of nerves. With these parameters, the normal nerve structures showed high signal intensity, while the blood vessels and muscles were effectively suppressed. The optimized D-prep MRN sequence clearly showed the three-dimensional trajectory of the brachial plexus, lumbosacral plexus, and cranial nerves. D-prep MRN was introduced and optimized, and clearly showed detailed anatomy of the brachial plexus, lumbosacral plexus, and cranial nerves. These results suggest that the D-prep MRN can be used for fast, high-resolution, volumetric imaging of the peripheral nervous system. (author)

Laser Giant Ion Source and the Prepulse Effects for Picosecond Interaction for High Gain Laser Fusion

International Nuclear Information System (INIS)

Hora, Heinrich; Badziak, J.; Parys, P.; Wolowski, J.; Woryna, E.; Boody, F.P.; Hoepfl, R.; Jungwirth, K.; Ullschmied, J.; Kralikova, B.; Krasa, J.; Laska, L.; Pfeifer, M.; Rohlena, K.; Skala, J.; Perina, V.

2003-01-01

By studying laser driven ion sources which produce giant ion emission current densities exceeding the few mA/cm2 of classical ion sources (MEVVA or ECR) by more than six orders of magnitude, we unexpectedly measured an anomalous low ion energy with ps laser pulses.The emission is basically different from that with the fastest ion energies in the MeV to GeV range due to relativistic self focusing and from the second fastest ion group due to quiver-thermalization processes. We report on specifically designed experiments with gold targets where 0.5 ns laser pulses produce MeV Au-ions in accordance with relativistic self focusing in strong contrast to ps pulses where a 400 times higher intensity from TW pulses is needed to arrive at the same ion energies. These can be explained by a basically new model without self-focusing as a skin layer effect where the absence of a prepulse is essential. This has consequences for the application of laser driven ion sources and may improve the hitherto highest published laser fusion gains with 50 TW-ps laser pulses without the usual spherical precompression

Chronic Toxoplasma gondii in Nurr1-null heterozygous mice exacerbates elevated open field activity.

Science.gov (United States)

Eells, Jeffrey B; Varela-Stokes, Andrea; Guo-Ross, Shirley X; Kummari, Evangel; Smith, Holly M; Cox, Erin; Lindsay, David S

2015-01-01

Latent infection with Toxoplasma gondii is common in humans (approximately 30% of the global population) and is a significant risk factor for schizophrenia. Since prevalence of T. gondii infection is far greater than prevalence of schizophrenia (0.5-1%), genetic risk factors are likely also necessary to contribute to schizophrenia. To test this concept in an animal model, Nurr1-null heterozygous (+/-) mice and wild-type (+/+) mice were evaluate using an emergence test, activity in an open field and with a novel object, response to bobcat urine and prepulse inhibition of the acoustic startle response (PPI) prior to and 6 weeks after infection with T. gondii. In the emergence test, T. gondii infection significantly decreased the amount of time spent in the cylinder. Toxoplasma gondii infection significantly elevated open field activity in both +/+ and +/- mice but this increase was significantly exacerbated in +/- mice. T. gondii infection reduced PPI in male +/- mice but this was not statistically significant. Aversion to bobcat urine was abolished by T. gondii infection in +/+ mice. In female +/- mice, aversion to bobcat urine remained after T. gondii infection while the male +/- mice showed no aversion to bobcat urine. Antibody titers of infected mice were a critical variable associated with changes in open field activity, such that an inverted U shaped relationship existed between antibody titers and the percent change in open field activity with a significant increase in activity at low and medium antibody titers but no effect at high antibody titers. These data demonstrate that the Nurr1 +/- genotype predisposes mice to T. gondii-induced alterations in behaviors that involve dopamine neurotransmission and are associated with symptoms of schizophrenia. We propose that these alterations in murine behavior were due to further exacerbation of the altered dopamine neurotransmission in Nurr1 +/- mice.

Chronic Toxoplasma gondii in Nurr1-null heterozygous mice exacerbates elevated open field activity.

Directory of Open Access Journals (Sweden)

Jeffrey B Eells

Full Text Available Latent infection with Toxoplasma gondii is common in humans (approximately 30% of the global population and is a significant risk factor for schizophrenia. Since prevalence of T. gondii infection is far greater than prevalence of schizophrenia (0.5-1%, genetic risk factors are likely also necessary to contribute to schizophrenia. To test this concept in an animal model, Nurr1-null heterozygous (+/- mice and wild-type (+/+ mice were evaluate using an emergence test, activity in an open field and with a novel object, response to bobcat urine and prepulse inhibition of the acoustic startle response (PPI prior to and 6 weeks after infection with T. gondii. In the emergence test, T. gondii infection significantly decreased the amount of time spent in the cylinder. Toxoplasma gondii infection significantly elevated open field activity in both +/+ and +/- mice but this increase was significantly exacerbated in +/- mice. T. gondii infection reduced PPI in male +/- mice but this was not statistically significant. Aversion to bobcat urine was abolished by T. gondii infection in +/+ mice. In female +/- mice, aversion to bobcat urine remained after T. gondii infection while the male +/- mice showed no aversion to bobcat urine. Antibody titers of infected mice were a critical variable associated with changes in open field activity, such that an inverted U shaped relationship existed between antibody titers and the percent change in open field activity with a significant increase in activity at low and medium antibody titers but no effect at high antibody titers. These data demonstrate that the Nurr1 +/- genotype predisposes mice to T. gondii-induced alterations in behaviors that involve dopamine neurotransmission and are associated with symptoms of schizophrenia. We propose that these alterations in murine behavior were due to further exacerbation of the altered dopamine neurotransmission in Nurr1 +/- mice.

Psychotomimetic effects of different doses of MK-801 and the underlying mechanisms in a selective memory impairment model.

Science.gov (United States)

Liu, Weiqing; Wang, Dong; Hong, Wenjuan; Yu, Yi; Tang, Jinsong; Wang, Jicai; Liu, Fang; Xu, Xiufeng; Tan, Liwen; Chen, Xiaogang

2017-03-01

Although N-methyl-d-aspartate receptor antagonists-induced hypoglutamate rodent models are the most well-established models for preclinical studies of schizophrenia-related deficits, they also evoke a wide spectrum of psychotomimetic side effects. It is significant to increase the specificity of hypoglutamate rodent models. In this study, the recognition memory was evaluated in rats by object recognition test (ORT), sensorimotor gating was evaluated by prepulse inhibition of the startle reflex (PPI), and locomotor activity was measured using open field test. High-performance liquid chromatography was used to measure neurotransmitters content in the medial prefrontal cortex (mPFC) and thalamus (THA). Total Akt and phospho-Akt protein was measured by Western blots. Results showed that 0.3mg/kg of MK-801 was most effective in inducing locomotion. 0.3mg/kg of MK-801 was most effective in decreasing PPI. 0.03mg/kg of MK-801 was most effective in decreasing object memory while not affecting exploration manners in the training session. 0.03mg/kg of MK-801 significantly increased HVA and Glu content in the mPFC. 0.1mg/kg of MK-801 significantly decreased GABA content in the THA. 0.03mg/kg of MK-801 significantly decreased Akt phosphorylation in the mPFC, which was related to the ORT index. In conclusion, a dose of 0.03mg/kg MK-801 can establish a "pure" memory impairment model without contaminations of sensorimotor gating and locomotor activity. MK-801-induced cognitive deficits is associated with increased DA metabolites and glutamate content in the mPFC and decreased GABA content in the THA as well as decrease in Akt phosphorylation in the mPFC. Copyright © 2016. Published by Elsevier B.V.

Establishment of a schizophrenic animal model through chronic administration of MK-801 in infancy and social isolation in childhood.

Science.gov (United States)

Liu, Weiqing; Wang, Xiuyan; Hong, Wenjuan; Wang, Dong; Chen, Xiaogang

2017-02-01

Although an increasing amount of evidence supports a "two-hit" hypothesis for the neurodevelopmental model of schizophrenia, there has been no development in animal models to test this hypothesis. An animal model was established by chronic administration of 0.1, 0.3, and 0.5mg/kg MK-801 in P7-P21 rats followed by four weeks of social isolation in childhood and then five days of social housing. Animal behaviors were measured by the open field (OF) test, the novel object recognition (NOR) test, the prepulse inhibition (PPI) test, and the elevated plus maze (EPM) test. We found a significant decrease in the NOR index in adolescent rats compared to saline control rats when administering 0.5mg/kg of MK-801 (P=0.02). We found that social isolation had no significant effect on NOR index, though social isolation significantly increased the total distance traveled and significantly decreased the resting time in adolescent rats in the OF test (Psocial isolation had no significant effect on the percent of PPI and startle amplitudes in adolescent rats. Social isolation significantly reduced the open arm entries in adolescent rats in the EPM test (P=0.023), but it did not reduce the ratio to enter the open arms and the stay time in open arm. Administration of MK-801 showed no significant effect on the indexes of entering the open arms in the EPM test on adolescent rats. MK-801 intervention in infancy is associated with the damage of long-term visual memory, whereas social isolation in childhood is associated with the increased spontaneous activity and anxiety levels. Administration of MK-801 in infancy and social isolation in childhood are two independent factors on the neurodevelopmental defects. Copyright © 2017 Elsevier Inc. All rights reserved.

Dexras1 a unique ras-GTPase interacts with NMDA receptor activity and provides a novel dissociation between anxiety, working memory and sensory gating.

Science.gov (United States)

Carlson, G C; Lin, R E; Chen, Y; Brookshire, B R; White, R S; Lucki, I; Siegel, S J; Kim, S F

2016-05-13

Dexras1 is a novel GTPase that acts at a confluence of signaling mechanisms associated with psychiatric and neurological disease including NMDA receptors, NOS1AP and nNOS. Recent work has shown that Dexras1 mediates iron trafficking and NMDA-dependent neurodegeneration but a role for Dexras1 in normal brain function or psychiatric disease has not been studied. To test for such a role, mice with germline knockout (KO) of Dexras1 were assayed for behavioral abnormalities as well as changes in NMDA receptor subunit protein expression. Because Dexras1 is up-regulated during stress or by dexamethasone treatment, we included measures associated with emotion including anxiety and depression. Baseline anxiety-like measures (open field and zero maze) were not altered, nor were depression-like behavior (tail suspension). Measures of memory function yielded mixed results, with no changes in episodic memory (novel object recognition) but a significant decrement on working memory (T-maze). Alternatively, there was an increase in pre-pulse inhibition (PPI), without concomitant changes in either startle amplitude or locomotor activity. PPI data are consistent with the direction of change seen following exposure to dopamine D2 antagonists. An examination of NMDA subunit expression levels revealed an increased expression of the NR2A subunit, contrary to previous studies demonstrating down-regulation of the receptor following antipsychotic exposure (Schmitt et al., 2003) and up-regulation after exposure to isolation rearing (Turnock-Jones et al., 2009). These findings suggest a potential role for Dexras1 in modulating a selective subset of psychiatric symptoms, possibly via its interaction with NMDARs and/or other disease-related binding-partners. Furthermore, data suggest that modulating Dexras1 activity has contrasting effects on emotional, sensory and cognitive domains. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Behavioral control by striatal adenosine A2A -dopamine D2 receptor heteromers.

Science.gov (United States)

Taura, J; Valle-León, M; Sahlholm, K; Watanabe, M; Van Craenenbroeck, K; Fernández-Dueñas, V; Ferré, S; Ciruela, F

2018-04-01

G protein-coupled receptors (GPCR) exhibit the ability to form receptor complexes that include molecularly different GPCR (ie, GPCR heteromers), which endow them with singular functional and pharmacological characteristics. The relative expression of GPCR heteromers remains a matter of intense debate. Recent studies support that adenosine A 2A receptors (A 2A R) and dopamine D 2 receptors (D 2 R) predominantly form A 2A R-D 2 R heteromers in the striatum. The aim of the present study was evaluating the behavioral effects of pharmacological manipulation and genetic blockade of A 2A R and D 2 R within the frame of such a predominant striatal heteromeric population. First, in order to avoid possible strain-related differences, a new D 2 R-deficient mouse with the same genetic background (CD-1) than the A 2A R knock-out mouse was generated. Locomotor activity, pre-pulse inhibition (PPI) and drug-induced catalepsy were then evaluated in wild-type, A 2A R and D 2 R knock-out mice, with and without the concomitant administration of either the D 2 R agonist sumanirole or the A 2A R antagonist SCH442416. SCH442416-mediated locomotor effects were demonstrated to be dependent on D 2 R signaling. Similarly, a significant dependence on A 2A R signaling was observed for PPI and for haloperidol-induced catalepsy. The results could be explained by the existence of one main population of striatal postsynaptic A 2A R-D 2 R heteromers, which may constitute a relevant target for the treatment of Parkinson's disease and other neuropsychiatric disorders. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Organization of film data processing in the PPI-SA automated system

International Nuclear Information System (INIS)

Ovsov, Yu.V.; Perekatov, V.G.

1984-01-01

Organization of processing nuclear interaction images at PUOS - type standard devices using the PPI-SA automated system is considered. The system is made in the form of a complete module comprising two scanning measuring projectors and a scan-ning automatic device which operate in real time on line with the BESM-4-computer. The system comprises: subsystem for photographic film scanning, selection of events for measurements and preliminary encoding; subsystem for formation and generation of libraries with data required for monitoring the scanning automatic device; subsystem for precision measurements separate coordinates on photo images of nuclear particle tracks and ionization losses. The system software comprises monitoring programs for the projectors and scanning automatic device as well as test functional control programs and operating system. The programs are organized a modular concept. By changing the module set the system can be modified and adapted for image processing in different fields of science and technology

Effects of cognitive-behavioural therapy (CBT) and positive psychological intervention (PPI) on female offenders with psychological distress in Hong Kong.

Science.gov (United States)

Mak, Vivian W M; Chan, Calais K Y

2018-04-01

Despite rapid growth in the female prison population, there is little research on effectiveness of psychological interventions for them. To test the hypotheses that (1) each of two psychological interventions administered separately - cognitive behavioural therapy (CBT) or positive psychology intervention (PPI) - would be more effective than 'treatment-as-usual' alone in reducing psychological distress and enhancing psychological well-being; (2) outcomes would differ according to intervention; and (3) combining the interventions would be more effective than delivering either alone. We recruited 40 women in a special Hong Kong prison unit for female offenders with psychological distress. Half of them received eight sessions of CBT followed by eight sessions of PPI; the other half received the same interventions in the reverse order. We recruited another 35 women who received only 'treatment as usual' (TAU) in the same unit. We used various clinical scales to assess the women's psychological distress or well-being before and after the interventions or at similar time points for the comparison women. All intervention group women showed a significant reduction in psychological distress and enhancement in psychological well-being after each intervention alone compared to the TAU women. There were no significant differences between CBT and PPI in this respect. Receiving both treatments, however, did yield significantly more improvement than either intervention alone in reducing depressive thoughts and enhancing global judgement of life satisfaction, self-perceived strengths and hopeful thinking style. Our findings provide preliminary empirical support for the effectiveness of psychological interventions with psychologically distressed women in prison. It would be important now to conduct a full, randomised trial to determine optimal length and combinations of treatment. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Alzheimer Europe's position on involving people with dementia in research through PPI (patient and public involvement)

DEFF Research Database (Denmark)

Gove, Dianne; Diaz-Ponce, Ana; Georges, Jean

2018-01-01

This paper reflects Alzheimer Europe's position on PPI (patient and public involvement) in the context of dementia research and highlights some of the challenges and potential risks and benefits associated with such meaningful involvement. The paper was drafted by Alzheimer Europe in collaboration...... with members of INTERDEM and the European Working Group of People with Dementia. It has been formally adopted by the Board of Alzheimer Europe and endorsed by the Board of INTERDEM and by the JPND working group 'Dementia Outcome Measures - Charting New Territory'. Alzheimer Europe is keen to promote...

1-Arylsulfonyl-2-(Pyridylmethylsulfinyl) Benzimidazoles as New Proton Pump Inhibitor Prodrugs

Science.gov (United States)

Shin, Jai Moo; Sachs, George; Cho, Young-moon; Garst, Michael

2010-01-01

New arylsulfonyl proton pump inhibitor (PPI) prodrug forms were synthesized. These prodrugs provided longer residence time of an effective PPI plasma concentration, resulting in better gastric acid inhibition. PMID:20032890

Analyzing the experiences of adolescent control rats: Effects of the absence of physical or social stimulation on anxiety-like behaviour are dependent on the test.

Science.gov (United States)

Joshi, Namrata; Leslie, Ronald A; Perrot, Tara S

2017-10-01

The present study was designed to systematically assess the control experience routinely used in our laboratory as part of studies on predator odour stress. Specifically, we examined effects of the physical and social components of this control experience on measures of anxiety-like behaviour in adolescent rats. Adolescent animals are at increased susceptibility to environmental perturbations and have been used for such studies much less often. Long-Evans rats of both sexes were subjected to physical stimulation (Exposed or Unexposed) and social stimulation (Single-Housed or Pair-Housed), resulting in four groups. Exposed rats received six 30-min exposures to an enclosed arena containing an unscented piece of cat collar occurring between adolescence and early adulthood, while Unexposed remained in the home cage. Groups of Exposed and Unexposed animals were housed singly (Single-Housed) from early adolescence to early adulthood or Pair-Housed during this time. Experimental procedures began in adolescence and involved repeated assessment of startle amplitude (measure of anxiety-like behaviour) and prepulse inhibition (PPI; a measure of sensorimotor gating) to gauge the short-term impact of social and/or physical stimulation. All animals were re-paired in adulthood prior to a final startle/PPI session to assess if isolation limited to adolescence could impose long-term effects that were not reversible. We also measured anxiety-like behaviour in adulthood using an extended open field test (EOFT; addition of novel objects to the open field on later days), and the elevated plus maze task (EPM), as well as a sucrose preference test (SPT) to measure anhedonia. An absence of social or physical stimulation resulted in increased startle amplitude and some measures of anxiety-like behaviour in the EOFT, but a reduction in such anxiety-like behaviour in the EPM task. These results suggest common neural substrates for the physical and social experiences. Performance in the SPT

Central role of pyrophosphate in acellular cementum formation.

Directory of Open Access Journals (Sweden)

Brian L Foster

Full Text Available Inorganic pyrophosphate (PP(i is a physiologic inhibitor of hydroxyapatite mineral precipitation involved in regulating mineralized tissue development and pathologic calcification. Local levels of PP(i are controlled by antagonistic functions of factors that decrease PP(i and promote mineralization (tissue-nonspecific alkaline phosphatase, Alpl/TNAP, and those that increase local PP(i and restrict mineralization (progressive ankylosis protein, ANK; ectonucleotide pyrophosphatase phosphodiesterase-1, NPP1. The cementum enveloping the tooth root is essential for tooth function by providing attachment to the surrounding bone via the nonmineralized periodontal ligament. At present, the developmental regulation of cementum remains poorly understood, hampering efforts for regeneration. To elucidate the role of PP(i in cementum formation, we analyzed root development in knock-out ((-/- mice featuring PP(i dysregulation.Excess PP(i in the Alpl(-/- mouse inhibited cementum formation, causing root detachment consistent with premature tooth loss in the human condition hypophosphatasia, though cementoblast phenotype was unperturbed. Deficient PP(i in both Ank and Enpp1(-/- mice significantly increased cementum apposition and overall thickness more than 12-fold vs. controls, while dentin and cellular cementum were unaltered. Though PP(i regulators are widely expressed, cementoblasts selectively expressed greater ANK and NPP1 along the root surface, and dramatically increased ANK or NPP1 in models of reduced PP(i output, in compensatory fashion. In vitro mechanistic studies confirmed that under low PP(i mineralizing conditions, cementoblasts increased Ank (5-fold and Enpp1 (20-fold, while increasing PP(i inhibited mineralization and associated increases in Ank and Enpp1 mRNA.Results from these studies demonstrate a novel developmental regulation of acellular cementum, wherein cementoblasts tune cementogenesis by modulating local levels of PP(i, directing and

Acetate Activation in Methanosaeta thermophila: Characterization of the Key Enzymes Pyrophosphatase and Acetyl-CoA Synthetase

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Stefanie Berger

2012-01-01

Full Text Available The thermophilic methanogen Methanosaeta thermophila uses acetate as sole substrate for methanogenesis. It was proposed that the acetate activation reaction that is needed to feed acetate into the methanogenic pathway requires the hydrolysis of two ATP, whereas the acetate activation reaction in Methanosarcina sp. is known to require only one ATP. As these organisms live at the thermodynamic limit that sustains life, the acetate activation reaction in Mt. thermophila seems too costly and was thus reevaluated. It was found that of the putative acetate activation enzymes one gene encoding an AMP-forming acetyl-CoA synthetase was highly expressed. The corresponding enzyme was purified and characterized in detail. It catalyzed the ATP-dependent formation of acetyl-CoA, AMP, and pyrophosphate (PPi and was only moderately inhibited by PPi. The breakdown of PPi was performed by a soluble pyrophosphatase. This enzyme was also purified and characterized. The pyrophosphatase hydrolyzed the major part of PPi (KM=0.27±0.05 mM that was produced in the acetate activation reaction. Activity was not inhibited by nucleotides or PPi. However, it cannot be excluded that other PPi-dependent enzymes take advantage of the remaining PPi and contribute to the energy balance of the cell.

Study of the O(N) linear σ model at finite temperature using the 2PPI expansion

International Nuclear Information System (INIS)

Verschelde, H.; De Pessemier, J.

2002-01-01

We show that a new expansion, which sums seagull and bubble graphs to all orders, can be applied to the O(N) linear σ-model at finite temperature. We prove that this expansion can be renormalized with the usual counterterms in a mass independent scheme and that Goldstone's theorem is satisfied at each order. At the one loop order of this expansion, the Hartree result for the effective potential (daisy and superdaisy graphs) is recovered. We show that at one loop 2PPI order, the self-energy of the σ-meson can be calculated exactly and that diagrams are summed beyond the Hartree approximation. (orig.)

Neonatal Amygdala Lesions and Stress Responsivity in Rats : Relevance to schizophrenia

NARCIS (Netherlands)

Terpstra, Jeroen

2004-01-01

"Stress responsiveness in an animal model with relevance to schizophrenia” Rats bearing lesions of the amygdala made on postnatal day 7 (D7 AMX) model aspects of neurodevelopmental psychopathologies, such as schizophrenia. Adult D7 AMX rats display impaired pre-pulse inhibition, impaired

Radiation recall gastritis secondary to combination of gemcitabine and erlotinib in pancreatic cancer and response to PPI - a case report.

Science.gov (United States)

Choi, Seong Ji; Kim, Hyo Jung; Kim, Jae Seon; Bak, Young-Tae; Kim, Jun Suk

2016-08-02

Radiation recall gastritis is rare but can be induced after concurrent chemoradiation for pancreatic cancer. We report a patient with pancreatic cancer who developed radiation-recall gastritis related to a combination of gemcitabine and erlotinib. A 54-year-old female with unresectable pancreatic cancer received gemcitabine in combination with radiation therapy followed by chemotherapy with gemcitabine and erlotinib. After completing 2 cycles of chemotherapy, the patient had epigastric pain, nausea, and vomiting. Abdominal computed tomography (CT) scan revealed diffuse wall thickening of the stomach, and esophagogastroduodenoscopy (EGD) showed multiple gastric ulcers. The patient was treated with proton pump inhibitors (PPI) and was continued on maintenance chemotherapy. Two months later, the patient presented with the similar symptoms and persistent gastric ulcers were observed during subsequent EGD. Nevertheless, the patient's symptom had resolved with PPI therapy. Thus, the patient underwent maintenance chemotherapy with gemcitabine and erlotinib for additional 4 cycles. Eventually, follow-up abdominal CT Scan and EGD at 6 months demonstrated resolution of the gastric ulcers. Physicians should be aware of the possibility of radiation recall gastritis associated with a combination of gemcitabine and erlotinib. Administration of PPIs may mitigate the adverse effects of gemcitabine and erlotinib in the presence of radiation recall gastritis; however further studies are warranted.

Radiation recall gastritis secondary to combination of gemcitabine and erlotinib in pancreatic cancer and response to PPI - a case report

International Nuclear Information System (INIS)

Choi, Seong Ji; Kim, Hyo Jung; Kim, Jae Seon; Bak, Young-Tae; Kim, Jun Suk

2016-01-01

Radiation recall gastritis is rare but can be induced after concurrent chemoradiation for pancreatic cancer. We report a patient with pancreatic cancer who developed radiation-recall gastritis related to a combination of gemcitabine and erlotinib. A 54-year-old female with unresectable pancreatic cancer received gemcitabine in combination with radiation therapy followed by chemotherapy with gemcitabine and erlotinib. After completing 2 cycles of chemotherapy, the patient had epigastric pain, nausea, and vomiting. Abdominal computed tomography (CT) scan revealed diffuse wall thickening of the stomach, and esophagogastroduodenoscopy (EGD) showed multiple gastric ulcers. The patient was treated with proton pump inhibitors (PPI) and was continued on maintenance chemotherapy. Two months later, the patient presented with the similar symptoms and persistent gastric ulcers were observed during subsequent EGD. Nevertheless, the patient’s symptom had resolved with PPI therapy. Thus, the patient underwent maintenance chemotherapy with gemcitabine and erlotinib for additional 4 cycles. Eventually, follow-up abdominal CT Scan and EGD at 6 months demonstrated resolution of the gastric ulcers. Physicians should be aware of the possibility of radiation recall gastritis associated with a combination of gemcitabine and erlotinib. Administration of PPIs may mitigate the adverse effects of gemcitabine and erlotinib in the presence of radiation recall gastritis; however further studies are warranted

A highly acid-resistant novel strain of Lactobacillus johnsonii No. 1088 has antibacterial activity, including that against Helicobacter pylori, and inhibits gastrin-mediated acid production in mice

Science.gov (United States)

Aiba, Yuji; Nakano, Yasuhiro; Koga, Yasuhiro; Takahashi, Kenji; Komatsu, Yasuhiko

2015-01-01

A novel strain of Lactobacillus johnsonii No. 1088 was isolated from the gastric juice of a healthy Japanese male volunteer, and characterized for its effectiveness in the stomach environment. Lactobacillus johnsonii No. 1088 was found to have the strongest acid resistance among several lactobacilli examined (>10% of cells survived at pH 1.0 after 2 h), and such a high acid resistance property was a specific characteristic of this strain of L. johnsonii. When cultured with various virulent bacteria, L. johnsonii No. 1088 inhibited the growth of Helicobacter pylori,Escherichia coli O-157, Salmonella Typhimurium, and Clostridium difficile, in which case its effectiveness was more potent than that of a type strain of L. johnsonii,JCM2012. In addition to its effect in vitro, L. johnsonii No. 1088 inhibited the growth of H. pylori in human intestinal microbiota-associated mice in both its live and lyophilized forms. Moreover, L. johnsonii No. 1088 suppressed gastric acid secretion in mice via decreasing the number of gastrin-positive cells in the stomach. These results taken together suggest that L. johnsonii No. 1088 is a unique lactobacillus having properties beneficial for supporting H. pylori eradication by triple therapy including the use of a proton pump inhibitor (PPI) and also for prophylaxis of gastroesophageal reflux disease possibly caused after H. pylori eradication as a side effect of PPI. PMID:25771812

A Preclinical Study of Casein Glycomacropeptide as a Dietary Intervention for Acute Mania

DEFF Research Database (Denmark)

Liebenberg, Nico; Jensen, Erik; Larsen, Erik Roj

2018-01-01

orally at 2, 4, or 8 h or for 1 week chronically. Amino acid and monoamine levels were measured in plasma and brain and behavior was assessed in the amphetamine-hyperlocomotion, forced swim, prepulse inhibition, and elevated plus maze tests. Results: Casein glycomacropeptide induced a time...

Effects of damage to auditory cortex on the discrimination of speech sounds by rats

Czech Academy of Sciences Publication Activity Database

Floody, O. R.; Ouda, Ladislav; Porter, B. A.; Kilgard, M. P.

2010-01-01

Roč. 101, č. 2 (2010), s. 260-268 ISSN 0031-9384 R&D Projects: GA ČR GA309/07/1336 Institutional research plan: CEZ:AV0Z50390703 Keywords : auditory cortex * brain lesions * prepulse inhibition Subject RIV: FH - Neurology Impact factor: 2.891, year: 2010

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

Full Text Available Background/Aims: Glucose-stimulated insulin secretion (GSIS of pancreatic β-cells involves glucose uptake and metabolism, closure of KATP channels and depolarization of the cell membrane potential (Vmem, activation of voltage-activated Ca2+ currents (ICav and influx of Ca2+, which eventually triggers hormone exocytosis. Beside this classical pathway, KATP-independent mechanisms such as changes in intracellular pH (pHi or cell volume, which also affect β-cell viability, can elicit or modify insulin release. In β-cells the regulation of pHi is mainly accomplished by Na+/H+ exchangers (NHEs. To investigate if other proton extrusion mechanisms than NHEs are involved in pH regulation, we tested for the presence of the non-gastric H+/K+ ATPase in rat insulinoma cells and assessed effects of the H+/K+ ATPase inhibitor SCH-28080 on insulin secretion, cell viability and apoptosis. Methods: In INS-1E cell cultures, H+/K+ ATPase gene and protein expression was analyzed by reverse transcription PCR and Western blotting. Intracellular pH (pHi recovery after acute acidic load was measured by NH4Cl prepulsing using BCECF. Insulin secretion was determined by ELISA from the cell culture supernatant. Vmem, K+ and Ca2+ currents were recorded using patch clamp. Overall cell responses were determined using resazurin (viability and cytotoxicity assays. The mean cell volume (MCV, cell granularity (side-scatter; SSC, phosphatidylserine (PS exposure, cell membrane integrity, caspase activity and the mitochondrial membrane potential (ΔΨm were measured by flow cytometry. Results: We found that the α-subunit of the non-gastric H+/K+ ATPase (HKα2 is expressed on mRNA and protein level. However, compared to rat colon tissue, in INS-1E cells mRNA abundance was very low. In NH4Cl prepulsing experiments no K+-dependent pHi recovery was observed under Na+-free extracellular conditions. Nonetheless within 1 h, 20 µM SCH-28080 inhibited GSIS by ∼50%, while basal release

Nature-inspired multifunctional membrane fabricated by adaptive hybridization of PNIPAm and PPy

Science.gov (United States)

Kim, Hyejeong; Kim, Kiwoong; Lee, Sang Joon

2017-11-01

Specialized plant organs, such as guard cells of stomata, consist of soft materials with deformability and electrochemical properties in response to various environmental stimuli. Stimulus-responsive hydrogels with electrochemical properties are good candidates for imitating such functionalities having great potential in a wide range of applications. However, conductive hydrogels are usually mechanically rigid and the fabrication technology of structured hydrogels has low reproducibility. Here, inspired by stimulus-responsive functionalities of plants, a thermo-responsive multifunctional hybrid membrane (HM) is synthesized through the in situ hybridization of conductive poly(pyrrole)(PPy) on a photopolymerized poly(N-isopropylacrylamide)(PNIPAm) membrane. The various properties of the HM are investigated to characterize its multiple functions. In terms of morphology, the HM can be easily fabricated into various structures, and exhibits thermo-responsive deformability. In terms of functionality, it exhibits various electrical and charge responses to thermal stimuli. This simple and efficient fabrication method can be used as a promising platform for fabricating a variety of functional devices, such as actuators, biosensors, and filtration membranes. This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean government (MSIP) (No. 2017R1A2B3005415).

Prenatal IV Cocaine: Alterations in Auditory Information Processing

Directory of Open Access Journals (Sweden)

Charles F. Mactutus

2011-06-01

Full Text Available One clue regarding the basis of cocaine-induced deficits in attentional processing is provided by the clinical findings of changes in the infants’ startle response; observations buttressed by neurophysiological evidence of alterations in brainstem transmission time. Using the IV route of administration and doses that mimic the peak arterial levels of cocaine use in humans, the present study examined the effects of prenatal cocaine on auditory information processing via tests of the acoustic startle response (ASR, habituation, and prepulse inhibition (PPI in the offspring. Nulliparous Long-Evans female rats, implanted with an IV access port prior to breeding, were administered saline, 0.5, 1.0, or 3.0 mg/kg/injection of cocaine HCL (COC from gestation day (GD8-20 (1x/day-GD8-14, 2x/day-GD15-20. COC had no significant effects on maternal/litter parameters or growth of the offspring. At 18-20 days of age, one male and one female, randomly selected from each litter displayed an increased ASR (>30% for males at 1.0 mg/kg and >30% for females at 3.0 mg/kg. When reassessed in adulthood (D90-100, a linear dose-response increase was noted on response amplitude. At both test ages, within-session habituation was retarded by prenatal cocaine treatment. Testing the females in diestrus vs. estrus did not alter the results. Prenatal cocaine altered the PPI response function across interstimulus interval (ISI and induced significant sex-dependent changes in response latency. Idazoxan, an alpha2-adrenergic receptor antagonist, significantly enhanced the ASR, but less enhancement was noted with increasing doses of prenatal cocaine. Thus, in utero exposure to cocaine, when delivered via a protocol designed to capture prominent features of recreational usage, causes persistent, if not permanent, alterations in auditory information processing, and suggests dysfunction of the central noradrenergic circuitry modulating, if not mediating, these responses.

Antipsychotic potential of quinazoline ErbB1 inhibitors in a schizophrenia model established with neonatal hippocampal lesioning.

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Mizuno, Makoto; Iwakura, Yuriko; Shibuya, Masako; Zheng, Yingjun; Eda, Takeyoshi; Kato, Taisuke; Takasu, Yohei; Nawa, Hiroyuki

2010-01-01

Hyper-signaling of the epidermal growth factor receptor family (ErbB) is implicated in the pathophysiology of schizophrenia. Various quinazoline inhibitors targeting ErbB1 or ErbB2 - 4 have been developed as anti-cancer agents and might be useful for antipsychotic treatment. In the present study, we used an animal model of schizophrenia established by neonatal hippocampal lesioning and evaluated the neurobehavioral consequences of ErbB1-inhibitor treatment. Subchronic administration of the ErbB1 inhibitor ZD1839 to the cerebroventricle of rats receiving neonatal hippocampal lesioning ameliorated deficits in prepulse inhibition as well as those in the latent inhibition of tone-dependent fear learning. There were no apparent adverse effects on basal learning scores or locomotor activity, however. The administration of other ErbB1 inhibitors, PD153035 and OSI-774, similarly attenuated the prepulse inhibition impairment of this animal model. In parallel, there were decreases in ErbB1 phosphorylation in animals treated with ErbB1 inhibitors. These results indicate an antipsychotic potential of quinazoline ErbB1 inhibitors. ErbB receptor tyrosine kinases may be novel therapeutic targets for schizophrenia or its related psychotic symptoms.

Prediction of response to PPI therapy and factors influencing treatment outcome in patients with GORD: a prospective pragmatic trial using pantoprazole

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Tholen Anne

2011-05-01

Full Text Available Abstract Background Management of patients with gastro-oesophageal reflux disease (GORD can be assisted by information predicting the likely response to proton pump inhibitor (PPI treatment. The aim was to undertake a study of GORD patients designed to approximate ordinary clinical practice that would identify patient characteristics predicting symptomatic response to pantoprazole treatment. Methods 1888 patients with symptoms of GORD were enrolled in a multicentre, multinational, prospective, open study of 8 weeks pantoprazole treatment, 40 mg daily. Response was assessed by using the ReQuest™ questionnaire, by the investigator making conventional clinical enquiry and by asking patients about their satisfaction with symptom control. Factors including pre-treatment oesophagitis, gender, age, body mass index (BMI, Helicobacter pylori status, anxiety and depression, and concurrent IBS symptoms were examined using logistic regression to determine if they were related to response, judged from the ReQuest™-GI score. Results Poorer treatment responses were associated with non-erosive reflux disease, female gender, lower BMI, anxiety and concurrent irritable bowel syndrome symptoms before treatment. No association was found with age, Helicobacter pylori status or oesophagitis grade. Some reflux-related symptoms were still present in 14% of patients who declared themselves 'well-satisfied' with their symptom control. Conclusions Some readily identifiable features help to predict symptomatic responses to a PPI and consequently may help in managing patient expectation. ClinicalTrial.gov identifier: NCT00312806.

Does Neonatal Brain Ischemia Induce Schizophrenia-Like Behavior in Young Adult Rats?

Czech Academy of Sciences Publication Activity Database

Tejkalová, H.; Kaiser, M.; Klaschka, Jan; Šťastný, František

2007-01-01

Roč. 56, č. 6 (2007), s. 815-823 ISSN 0862-8408 R&D Projects: GA MZd(CZ) NR8797 Institutional research plan: CEZ:AV0Z10300504; CEZ:AV0Z50110509 Keywords : neonatal ischemia * schizophrenia * rat * prepulse inhibition Subject RIV: FL - Psychiatry, Sexuology Impact factor: 1.505, year: 2007

Enhanced inhibitory effects of TBT chloride on the development of F1 rats.

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Asakawa, H; Tsunoda, M; Kaido, T; Hosokawa, M; Sugaya, C; Inoue, Y; Kudo, Y; Satoh, T; Katagiri, H; Akita, H; Saji, M; Wakasa, M; Negishi, T; Tashiro, T; Aizawa, Y

2010-05-01

Neurotoxicity is one of the major effects of tributyltin (TBT). The effects on the next generation of F(1) rats exposed to TBT via the placenta and their dams' milk may be stronger than those on adults. Pregnant Wister rats were exposed to TBT at 0 and 125 ppm in their food. Half of the female F(1) rats in both groups were exposed to TBT at 125 ppm in their food from 9 to 15 weeks of age. Female F(1) rats were divided into the following groups: the control-control (CC) group, with no exposure; the TBT-control (TC) group, exposed to TBT via the placenta and their dams' milk; the control-TBT (CT) group, exposed to TBT via their food from 9 to 15 weeks of age; and the TBT-TBT (TT) group, exposed to TBT via the placenta, their dams' milk, and their food (n = 10/group). After administration, an open-field test and prepulse inhibition (PPI) test were performed at 15 weeks of age. The mean body weights of the TC and TT groups were significantly lower than that of the CC group from 9 to 15 weeks of age. The mean relative thymus weight of the TC and TT groups was significantly lower than that of the CC group. In the open-field test, a marked decrease in the total locomotion distance was observed in the TT group. The mean values in the TT and TC groups were significantly lower than that in the CC group. For the locomotion distance between 15 and 20 min, the mean values in the CT, TC, and TT groups were significantly lower than that in the CC group. The mean locomotor distance between 25 and 30 min in the TT group was significantly lower than that in the CC and TC groups. The mean values of instances of wall rearing in the TC, CT, and TT groups were significantly lower than that in the CC group. The mean value of face washing or body washing in the TT group was significantly lower than that in the CT group. There were no significant differences in indexes of the PPI test. Exposure to TBT via the placenta and their dams' milk inhibited the development of F(1) rats, which

Modulation ofTcf7l2 expression alters behavior in mice.

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Daniel Savic

Full Text Available The comorbidity of type 2 diabetes (T2D with several psychiatric diseases is well established. While environmental factors may partially account for these co-occurrences, common genetic susceptibilities could also be implicated in the confluence of these diseases. In support of shared genetic burdens, TCF7L2, the strongest genetic determinant for T2D risk in the human population, has been recently implicated in schizophrenia (SCZ risk, suggesting that this may be one of many loci that pleiotropically influence both diseases. To investigate whether Tcf7l2 is involved in behavioral phenotypes in addition to its roles in glucose metabolism, we conducted several behavioral tests in mice with null alleles of Tcf7l2 or overexpressing Tcf7l2. We identified a role for Tcf7l2 in anxiety-like behavior and a dose-dependent effect of Tcf7l2 alleles on fear learning. None of the mutant mice showed differences in prepulse inhibition (PPI, which is a well-established endophenotype for SCZ. These results show that Tcf7l2 alters behavior in mice. Importantly, these differences are observed prior to the onset of detectable glucose metabolism abnormalities. Whether these differences are related to human anxiety-disorders or schizophrenia remains to be determined. These animal models have the potential to elucidate the molecular basis of psychiatric comorbidities in diabetes and should therefore be studied further.

Development of a novel biosensor based on a polypyrrole-dodecylbenzene sulphonate (PPy-DBS) film for the determination of amperometric cholesterol.

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Özer, Bayram Oğuz; Çete, Servet

2017-06-01

Herein a novel amperometric biosensor based on a conducting polymer with anionic dopant modified electrode was successfully developed for detection of cholesterol. Polypyrrole is deposited on a platinum surface and the sodium dodecylbenzene sulphonate (DBS) ion-doped polypyrrole film was electrochemically prepared by scanning the electrode potential between -0.8 and +0.8 V at a scan rate of 20 mV/s. The present electrochemical biosensor was optimized in terms of working potential, number of cycles, concentrations of monomer, and anionic dopant. Cholesterol oxidase (ChOx) was physically entrapped in PPy-DBS to construct an amperometric cholesterol biosensor. Amperometric determination is based on the electrochemical detection of H 2 O 2 generated in the enzymatic reaction of cholesterol. Kinetic parameters, operational and storage stabilities, pH, and temperature dependencies were determined. Km and Imax were calculated as 0.11 μM and 0.967 nM/min, respectively. The operational stability results showed that 90.0% of the response current was retained after 30 activity assays. Morphology of electrodes was characterized by SEM and AFM. Additionally, contact angle measurements were made with 1 μL water of polymer film and enzyme electrode. As a result, the cholesterol biosensor suggested in this study is easy to prepare and is highly cost-effective. This composite (PPy-DBS) can supply a biocompatible and electrochemical microenvironment for immobilization of the enzyme, making this material a good candidate for the fabrication of highly sensitive and selective cholesterol biosensors.

Yi-gan san restores behavioral alterations and a decrease of brain glutathione level in a mouse model of schizophrenia.

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Makinodan, Manabu; Yamauchi, Takahira; Tatsumi, Kouko; Okuda, Hiroaki; Noriyama, Yoshinobu; Sadamatsu, Miyuki; Kishimoto, Toshifumi; Wanaka, Akio

2009-01-01

The traditional Chinese herbal medicine yi-gan san has been used to cure neuropsychological disorders. Schizophrenia can be one of the target diseases of yi-gan san. We aimed at evaluating the possible use of yi-gan san in improving the schizophrenic symptoms of an animal model. Yi-gan san or distilled water was administered to mice born from pregnant mice injected with polyinosinic-polycytidilic acid or phosphate buffered saline. The former is a model of schizophrenia based on the epidemiological data that maternal infection leads to psychotic disorders including schizophrenia in the offspring. Prepulse inhibition and sensitivity to methamphetamine in open field tests were analyzed and the total glutathione content of whole brains was measured. Yi-gan san reversed the decrease in prepulse inhibition, hypersensitivity to methamphetamine and cognitive deficits found in the model mice to the level of control mice. Total glutathione content in whole brains was reduced in the model mice but was restored to normal levels by yi-gan san treatment. These results suggest that yi-gan san may have ameliorating effects on the pathological symptoms of schizophrenia.

Evaluation of cytotoxicity of polypyrrole nanoparticles synthesized by oxidative polymerization

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Vaitkuviene, Aida [Department of Physical Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, LT-03225 Vilnius (Lithuania); Department of Stem Cell Biology, State Research Institute Center for Innovative Medicine, Zygimantu 9, LT-01102 Vilnius (Lithuania); Kaseta, Vytautas [Department of Stem Cell Biology, State Research Institute Center for Innovative Medicine, Zygimantu 9, LT-01102 Vilnius (Lithuania); Voronovic, Jaroslav [Department of Physical Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, LT-03225 Vilnius (Lithuania); Ramanauskaite, Giedre; Biziuleviciene, Gene [Department of Stem Cell Biology, State Research Institute Center for Innovative Medicine, Zygimantu 9, LT-01102 Vilnius (Lithuania); Ramanaviciene, Almira [NanoTechnas–Center of Nanotechnology and Material Science at Department of Analytical and Environmental Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, 03225 Vilnius (Lithuania); Ramanavicius, Arunas, E-mail: Arunas.Ramanavicius@chf.vu.lt [Department of Physical Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, LT-03225 Vilnius (Lithuania); Laboratory of BioNanoTechnology, Department of Materials Science and Electronics, Institute of Semiconductor Physics, State Scientific Research Institute Centre for Physical Sciences and Technology, A. Gostauto 11, LT-01108 Vilnius (Lithuania)

2013-04-15

Highlights: ► Polypyrrole nanoparticles synthesized by environmentally friendly polymerization at high concentrations are cytotoxic. ► Primary mouse embryonic fibroblast, mouse hepatoma and human T lymphocyte Jurkat cell lines were treated by Ppy nanoparticles. ► Polypyrrole nanoparticles at high concentrations inhibit cell proliferation. -- Abstract: Polypyrrole (Ppy) is known as biocompatible material, which is used in some diverse biomedical applications and seeming to be a very promising for advanced biotechnological applications. In order to increase our understanding about biocompatibility of Ppy, in this study pure Ppy nanoparticles (Ppy-NPs) of fixed size and morphology were prepared by one-step oxidative polymerization and their cyto-compatibility was evaluated. The impact of different concentration of Ppy nanoparticles on primary mouse embryonic fibroblasts (MEF), mouse hepatoma cell line (MH-22A), and human T lymphocyte Jurkat cell line was investigated. Cell morphology, viability/proliferation after the treatment by Ppy nanoparticles was evaluated. Obtained results showed that Ppy nanoparticles at low concentrations are biocompatible, while at high concentrations they became cytotoxic for Jurkat, MEF and MH-22A cells, and it was found that cytotoxic effect is dose-dependent.

A Comparison of Alkaline Water and Mediterranean Diet vs Proton Pump Inhibition for Treatment of Laryngopharyngeal Reflux.

Science.gov (United States)

Zalvan, Craig H; Hu, Shirley; Greenberg, Barbara; Geliebter, Jan

2017-10-01

Laryngopharyngeal reflux (LPR) is a common disorder with protean manifestations in the head and neck. In this retrospective study, we report the efficacy of a wholly dietary approach using alkaline water, a plant-based, Mediterranean-style diet, and standard reflux precautions compared with that of the traditional treatment approach of proton pump inhibition (PPI) and standard reflux precautions. To determine whether treatment with a diet-based approach with standard reflux precautions alone can improve symptoms of LPR compared with treatment with PPI and standard reflux precautions. This was a retrospective medical chart review of 2 treatment cohorts. From 2010 to 2012, 85 patients with LPR that were treated with PPI and standard reflux precautions (PS) were identified. From 2013 to 2015, 99 patients treated with alkaline water (pH >8.0), 90% plant-based, Mediterranean-style diet, and standard reflux precautions (AMS) were identified. The outcome was based on change in Reflux Symptom Index (RSI). Recorded change in the RSI after 6 weeks of treatment. Of the 184 patients identified in the PS and AMS cohorts, the median age of participants in each cohort was 60 years (95% CI, 18-82) and 57 years (95% CI, 18-93), respectively (47 [56.3%] and 61 [61.7%] were women, respectively). The percentage of patients achieving a clinically meaningful (≥6 points) reduction in RSI was 54.1% in PS-treated patients and 62.6% in AMS-treated patients (difference between the groups, 8.05; 95% CI, -5.74 to 22.76). The mean reduction in RSI was 27.2% for the PS group and 39.8% in the AMS group (difference, 12.10; 95% CI, 1.53 to 22.68). Our data suggest that the effect of PPI on the RSI based on proportion reaching a 6-point reduction in RSI is not significantly better than that of alkaline water, a plant-based, Mediterranean-style diet, and standard reflux precautions, although the difference in the 2 treatments could be clinically meaningful in favor of the dietary approach. The

The absence of brain-specific link protein Bral2 in perineuronal nets hampers auditory temporal resolution and neural adaptation in mice.

Czech Academy of Sciences Publication Activity Database

Popelář, Jiří; Gómez, M.D.; Lindovský, Jiří; Rybalko, Natalia; Burianová, Jana; Oohashi, T.; Syka, Josef

2017-01-01

Roč. 66, č. 5 (2017), s. 867-880 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA13-11867S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378041 Keywords : critical period * acoustic startle reflex * prepulse inhibition Subject RIV: FH - Neurology OBOR OECD: Forensic science Impact factor: 1.461, year: 2016

Biocomposites of nanofibrillated cellulose, polypyrrole, and silver nanoparticles with electroconductive and antimicrobial properties.

Science.gov (United States)

Bober, Patrycja; Liu, Jun; Mikkonen, Kirsi S; Ihalainen, Petri; Pesonen, Markus; Plumed-Ferrer, Carme; von Wright, Atte; Lindfors, Tom; Xu, Chunlin; Latonen, Rose-Marie

2014-10-13

In this work, flexible and free-standing composite films of nanofibrillated cellulose/polypyrrole (NFC/PPy) and NFC/PPy-silver nanoparticles (NFC/PPy-Ag) have been synthesized for the first time via in situ one-step chemical polymerization and applied in potential biomedical applications. Incorporation of NFC into PPy significantly improved its film formation ability resulting in composite materials with good mechanical and electrical properties. It is shown that the NFC/PPy-Ag composite films have strong inhibition effect against the growth of Gram-positive bacteria, e.g., Staphylococcus aureus. The electrical conductivity and strong antimicrobial activity makes it possible to use the silver composites in various applications aimed at biomedical treatments and diagnostics. Additionally, we report here the structural and morphological characterization of the composite materials with Fourier-transform infrared spectroscopy, atomic force microscopy, and scanning and transmission electron microscopy techniques.

Adeno-associated virus (AAV-mediated suppression of Ca2+/calmodulin kinase IV activity in the nucleus accumbens modulates emotional behaviour in mice

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Bading Hilmar

2007-12-01

Full Text Available Abstract Background Calcium/calmodulin-dependent protein kinase IV (CaMKIV controls activity-dependent gene transcription by regulating the activity of the cyclic AMP response element binding protein (CREB. This signaling pathway is involved in gating emotional responses in the CNS but previous studies did not address the potential roles of CaMKIV in discrete brain regions. In the present study, we aimed at specifically dissecting the role of CaMKIV in the nucleus accumbens of adult mice. Results We used recombinant adeno-associated virus (rAAV-mediated gene transfer of a dominant-negative CaMKIV variant (rAAV-dnCaMKIV to inhibit endogenous CaMKIV in the nucleus accumbens. rAAV-dnCaMKIV treated animals were subjected to a battery of tests including, prepulse inhibition of the acoustic startle response, open field, social interaction and anxiety-related behaviour. We found that basal locomotor activity in the open field, and prepulse inhibition or startle performance were unaltered in mice infected with rAAV-dnCaMKIV in the nucleus accumbens. However, anxiogenic effects were revealed in social interaction testing and the light/dark emergence test. Conclusion Our findings suggest a modulatory role of CaMKIV in the nucleus accumbens in anxiety-like behaviour but not sensorimotor gating.

Up-regulated expression of cartilage intermediate-layer protein and ANK in articular hyaline cartilage from patients with calcium pyrophosphate dihydrate crystal deposition disease.

Science.gov (United States)

Hirose, Jun; Ryan, Lawrence M; Masuda, Ikuko

2002-12-01

Excess accumulation of extracellular inorganic pyrophosphate (ePPi) in aged human cartilage is crucial in calcium pyrophosphate dihydrate (CPPD) crystal formation in cartilage matrix. Two sources of ePPi are ePPi-generating ectoenzymes (NTPPPH) and extracellular transport of intracellular PPi by ANK. This study was undertaken to evaluate the role of NTPPPH and ANK in ePPi elaboration, by investigating expression of NTPPPH enzymes (cartilage intermediate-layer protein [CILP] and plasma cell membrane glycoprotein 1 [PC-1]) and ANK in human chondrocytes from osteoarthritic (OA) articular cartilage containing CPPD crystals and without crystals. Chondrocytes were harvested from knee cartilage at the time of arthroplasty (OA with CPPD crystals [CPPD], n = 8; OA without crystals [OA], n = 10). Normal adult human chondrocytes (n = 1) were used as a control. Chondrocytes were cultured with transforming growth factor beta1 (TGFbeta1), which stimulates ePPi elaboration, and/or insulin-like growth factor 1 (IGF-1), which inhibits ePPi elaboration. NTPPPH and ePPi were measured in the media at 48 hours. Media CILP, PC-1, and ANK were determined by dot-immunoblot analysis. Chondrocyte messenger RNA (mRNA) was extracted for reverse transcriptase-polymerase chain reaction to study expression of mRNA for CILP, PC-1, and ANK. NTPPPH and ANK mRNA and protein were also studied in fresh frozen cartilage. Basal ePPi elaboration and NTPPPH activity in conditioned media from CPPD chondrocytes were elevated compared with normal chondrocytes, and tended to be higher compared with OA chondrocytes. Basal expression of mRNA for CILP (chondrocytes) and ANK (cartilage) was higher in both CPPD chondrocytes and CPPD cartilage extract than in OA or normal samples. PC-1 mRNA was less abundant in CPPD chondrocytes and cartilage extract than in OA chondrocytes and extract, although the difference was not significant. CILP, PC-1, and ANK protein levels were similar in CPPD, OA, and normal chondrocytes

Monosialotetrahexosylganglioside Inhibits the Expression of p-CREB and NR2B in the Auditory Cortex in Rats with Salicylate-Induced Tinnitus.

Science.gov (United States)

Song, Rui-Biao; Lou, Wei-Hua

2015-01-01

This study investigated the effects of monosialotetrahexosylganglioside (GM1) on the expression of N-methyl-D-aspartate receptor subunit 2B (NR2B) and phosphorylated (p)-cyclic AMP response element-binding protein (CREB) in the auditory cortex of rats with tinnitus. Tinnitus-like behavior in rats was tested with the gap prepulse inhibition of acoustic startle paradigm. We then investigated the NR2B mRNA and protein and p-CREB protein levels in the auditory cortex of tinnitus rats compared with normal rats. Rats treated for 4 days with salicylate exhibited tinnitus. NR2B mRNA and protein and p-CREB protein levels were upregulated in these animals, with expression returning to normal levels 14 days after cessation of treatment; baseline levels of NR2B and p-CREB were also restored by GM1 administration. These data suggest that chronic salicylate administration induces tinnitus via upregulation of p-CREB and NR2B expression, and that GM1 can potentially be used to treat tinnitus.

Self-powered vision electronic-skin basing on piezo-photodetecting Ppy/PVDF pixel-patterned matrix for mimicking vision

Science.gov (United States)

Han, Wuxiao; Zhang, Linlin; He, Haoxuan; Liu, Hongmin; Xing, Lili; Xue, Xinyu

2018-06-01

The development of multifunctional electronic-skin that establishes human-machine interfaces, enhances perception abilities or has other distinct biomedical applications is the key to the realization of artificial intelligence. In this paper, a new self-powered (battery-free) flexible vision electronic-skin has been realized from pixel-patterned matrix of piezo-photodetecting PVDF/Ppy film. The electronic-skin under applied deformation can actively output piezoelectric voltage, and the outputting signal can be significantly influenced by UV illumination. The piezoelectric output can act as both the photodetecting signal and electricity power. The reliability is demonstrated over 200 light on–off cycles. The sensing unit matrix of 6 × 6 pixels on the electronic-skin can realize image recognition through mapping multi-point UV stimuli. This self-powered vision electronic-skin that simply mimics human retina may have potential application in vision substitution.

Self-powered vision electronic-skin basing on piezo-photodetecting Ppy/PVDF pixel-patterned matrix for mimicking vision.

Science.gov (United States)

Han, Wuxiao; Zhang, Linlin; He, Haoxuan; Liu, Hongmin; Xing, Lili; Xue, Xinyu

2018-06-22

The development of multifunctional electronic-skin that establishes human-machine interfaces, enhances perception abilities or has other distinct biomedical applications is the key to the realization of artificial intelligence. In this paper, a new self-powered (battery-free) flexible vision electronic-skin has been realized from pixel-patterned matrix of piezo-photodetecting PVDF/Ppy film. The electronic-skin under applied deformation can actively output piezoelectric voltage, and the outputting signal can be significantly influenced by UV illumination. The piezoelectric output can act as both the photodetecting signal and electricity power. The reliability is demonstrated over 200 light on-off cycles. The sensing unit matrix of 6 × 6 pixels on the electronic-skin can realize image recognition through mapping multi-point UV stimuli. This self-powered vision electronic-skin that simply mimics human retina may have potential application in vision substitution.

Temperature dependence of the triplet diffusion and quenching rates in films of an Ir(ppy)3 -cored dendrimer

Science.gov (United States)

Ribierre, J. C.; Ruseckas, A.; Samuel, I. D. W.; Staton, S. V.; Burn, P. L.

2008-02-01

We study photoluminescence and triplet-triplet exciton annihilation in a neat film of a fac-tris(2-phenylpyridyl)iridium(III) [Ir(ppy)3] -cored dendrimer and in its blend with a 4,4' -bis( N -carbazolyl)biphenyl host for the temperature range of 77-300K . The nearest neighbor hopping rate of triplet excitons is found to increase by a factor of 2 with temperature between 150 and 300K and is temperature independent at lower temperature. The intermolecular quenching rate follows the Arrhenius law with an activation energy of 7meV , which can be explained by stronger dipole-dipole interactions with the donor molecule in the higher triplet substate. The results indicate that energy disorder has no significant effect on triplet transport and quenching in these materials.

A novel modified electrode as GC/PPy-AuNPs-rGO/L-Cys/Ag@MUA nanostructure configuration for determination of CCP and CRP antibodies in human blood serum samples.

Science.gov (United States)

Babakhanian, Arash; Ehzari, Hosna; Kaki, Samineh; Hamidi, Zohreh

2015-01-15

In this work, silver nanoparticles were synthesized and stabilized with 11-mercaptoundecanoateanions to produce a new Ag@MUA core shell structure, and its utilizing for fabrication of a new sensing film. Gold nanoparticles (AuNPs) were electrochemically produced and simultaneously immobilized into the electropolymerized polypyrrole (PPy) film with the reduced graphene oxide (rGO). The Ag@MUA was then grafted to the surface of GC/PPy-AuNPs-rGO film using L-cysteine (L-Cys) linker agent and trifluoromethanesulfonic anhydride (TF2O), at ambient temperature and under the electrode stirring. The characterization of the sensor was studied by scanning electron microscopy, electrochemical impedance spectroscopy, cyclic and square wave voltammetry techniques. The utility of the modified electrode for clinical diagnosis has been successfully demonstrated by the analysis of human blood serums with a certified CRP and CCP content. Thus, the proposed sensor shows simple preparation, accuracy and precision in the analysis of cytochrome c protein (CCP) and C-reactive protein (CRP (with less side interferences. Copyright © 2014 Elsevier B.V. All rights reserved.

Electrically controlled drug release from nanostructured polypyrrole coated on titanium

International Nuclear Information System (INIS)

Sirivisoot, Sirinrath; Pareta, Rajesh; Webster, Thomas J

2011-01-01

Previous studies have demonstrated that multi-walled carbon nanotubes grown out of anodized nanotubular titanium (MWNT-Ti) can be used as a sensing electrode for various biomedical applications; such sensors detected the redox reactions of certain molecules, specifically proteins deposited by osteoblasts during extracellular matrix bone formation. Since it is known that polypyrrole (PPy) can release drugs upon electrical stimulation, in this study antibiotics (penicillin/streptomycin, P/S) or an anti-inflammatory drug (dexamethasone, Dex), termed PPy[P/S] or PPy[Dex], respectively, were electrodeposited in PPy on titanium. The objective of the present study was to determine if such drugs can be released from PPy on demand and (by applying a voltage) control cellular behavior important for orthopedic applications. Results showed that PPy films possessed nanometer-scale roughness as analyzed by atomic force microscopy. X-ray photoelectron spectroscopy confirmed the presence of P/S and Dex encapsulated within the PPy films. Results from cyclic voltammetry showed that 80% of the drugs were released on demand when sweep voltages were applied for five cycles at a scan rate of 0.1 V s -1 . Furthermore, osteoblast (bone-forming cells) and fibroblast (fibrous tissue-forming cells) adhesion were determined on the PPy films. Results showed that PPy[Dex] enhanced osteoblast adhesion after 4 h of culture compared to plain Ti. PPy-Ti (with or without anionic drug doping) inhibited fibroblast adhesion compared to plain Ti. These in vitro results confirmed that electrodeposited PPy[P/S] and PPy[Dex] can release drugs on demand to potentially fight bacterial infection, reduce inflammation, promote bone growth or reduce fibroblast functions, further implicating the use of such materials as implant sensors.

Electrically controlled drug release from nanostructured polypyrrole coated on titanium

Science.gov (United States)

Sirivisoot, Sirinrath; Pareta, Rajesh; Webster, Thomas J.

2011-02-01

Previous studies have demonstrated that multi-walled carbon nanotubes grown out of anodized nanotubular titanium (MWNT-Ti) can be used as a sensing electrode for various biomedical applications; such sensors detected the redox reactions of certain molecules, specifically proteins deposited by osteoblasts during extracellular matrix bone formation. Since it is known that polypyrrole (PPy) can release drugs upon electrical stimulation, in this study antibiotics (penicillin/streptomycin, P/S) or an anti-inflammatory drug (dexamethasone, Dex), termed PPy[P/S] or PPy[Dex], respectively, were electrodeposited in PPy on titanium. The objective of the present study was to determine if such drugs can be released from PPy on demand and (by applying a voltage) control cellular behavior important for orthopedic applications. Results showed that PPy films possessed nanometer-scale roughness as analyzed by atomic force microscopy. X-ray photoelectron spectroscopy confirmed the presence of P/S and Dex encapsulated within the PPy films. Results from cyclic voltammetry showed that 80% of the drugs were released on demand when sweep voltages were applied for five cycles at a scan rate of 0.1 V s - 1. Furthermore, osteoblast (bone-forming cells) and fibroblast (fibrous tissue-forming cells) adhesion were determined on the PPy films. Results showed that PPy[Dex] enhanced osteoblast adhesion after 4 h of culture compared to plain Ti. PPy-Ti (with or without anionic drug doping) inhibited fibroblast adhesion compared to plain Ti. These in vitro results confirmed that electrodeposited PPy[P/S] and PPy[Dex] can release drugs on demand to potentially fight bacterial infection, reduce inflammation, promote bone growth or reduce fibroblast functions, further implicating the use of such materials as implant sensors.

Electrically controlled drug release from nanostructured polypyrrole coated on titanium

Energy Technology Data Exchange (ETDEWEB)

Sirivisoot, Sirinrath; Pareta, Rajesh; Webster, Thomas J, E-mail: Thomas_Webster@Brown.edu [School of Engineering, Brown University, Providence, RI 02912 (United States)

2011-02-25

Previous studies have demonstrated that multi-walled carbon nanotubes grown out of anodized nanotubular titanium (MWNT-Ti) can be used as a sensing electrode for various biomedical applications; such sensors detected the redox reactions of certain molecules, specifically proteins deposited by osteoblasts during extracellular matrix bone formation. Since it is known that polypyrrole (PPy) can release drugs upon electrical stimulation, in this study antibiotics (penicillin/streptomycin, P/S) or an anti-inflammatory drug (dexamethasone, Dex), termed PPy[P/S] or PPy[Dex], respectively, were electrodeposited in PPy on titanium. The objective of the present study was to determine if such drugs can be released from PPy on demand and (by applying a voltage) control cellular behavior important for orthopedic applications. Results showed that PPy films possessed nanometer-scale roughness as analyzed by atomic force microscopy. X-ray photoelectron spectroscopy confirmed the presence of P/S and Dex encapsulated within the PPy films. Results from cyclic voltammetry showed that 80% of the drugs were released on demand when sweep voltages were applied for five cycles at a scan rate of 0.1 V s{sup -1}. Furthermore, osteoblast (bone-forming cells) and fibroblast (fibrous tissue-forming cells) adhesion were determined on the PPy films. Results showed that PPy[Dex] enhanced osteoblast adhesion after 4 h of culture compared to plain Ti. PPy-Ti (with or without anionic drug doping) inhibited fibroblast adhesion compared to plain Ti. These in vitro results confirmed that electrodeposited PPy[P/S] and PPy[Dex] can release drugs on demand to potentially fight bacterial infection, reduce inflammation, promote bone growth or reduce fibroblast functions, further implicating the use of such materials as implant sensors.

Yi-Gan San Restores Behavioral Alterations and a Decrease of Brain Glutathione Level in a Mouse Model of Schizophrenia

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Manabu Makinodan M.D.

2009-01-01

Full Text Available The traditional Chinese herbal medicine yi-gan san has been used to cure neuropsychological disorders. Schizophrenia can be one of the target diseases of yi-gan san. We aimed at evaluating the possible use of yi-gan san in improving the schizophrenic symptoms of an animal model. Yi-gan san or distilled water was administered to mice born from pregnant mice injected with polyinosinic-polycytidilic acid or phosphate buffered saline. The former is a model of schizophrenia based on the epidemiological data that maternal infection leads to psychotic disorders including schizophrenia in the offspring. Prepulse inhibition and sensitivity to methamphetamine in open field tests were analyzed and the total glutathione content of whole brains was measured. Yi-gan san reversed the decrease in prepulse inhibition, hypersensitivity to methamphetamine and cognitive deficits found in the model mice to the level of control mice. Total glutathione content in whole brains was reduced in the model mice but was restored to normal levels by yi-gan san treatment. These results suggest that yi-gan san may have ameliorating effects on the pathological symptoms of schizophrenia.

The effects of breeding protocol in C57BL/6J mice on adult offspring behaviour.

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Claire J Foldi

Full Text Available Animal experiments have demonstrated that a wide range of prenatal exposures can impact on the behaviour of the offspring. However, there is a lack of evidence as to whether the duration of sire exposure could affect such outcomes. We compared two widely used methods for breeding offspring for behavioural studies. The first involved housing male and female C57Bl/6J mice together for a period of time (usually 10-12 days and checking for pregnancy by the presence of a distended abdomen (Pair-housed; PH. The second involved daily introduction of female breeders to the male homecage followed by daily checks for pregnancy by the presence of vaginal plugs (Time-mated; TM. Male and female offspring were tested at 10 weeks of age on a behavioural test battery including the elevated plus-maze, hole board, light/dark emergence, forced swim test, novelty-suppressed feeding, active avoidance and extinction, tests for nociception and for prepulse inhibition (PPI of the acoustic startle response. We found that length of sire exposure (LSE had no significant effects on offspring behaviour, suggesting that the two breeding protocols do not differentially affect the behavioural outcomes of interest. The absence of LSE effects on the selected variables examined does not detract from the relevance of this study. Information regarding the potential influences of breeding protocol is not only absent from the literature, but also likely to be of particular interest to researchers studying the influence of prenatal manipulations on adult behaviour.

1996 Toxic Hazards Research Annual Report.

Science.gov (United States)

1998-01-01

gasoline , diesel fuel, and jet propulsion (JP) fuel (Staats, 1994). Millions of dollars are spent each year at petroleum contaminated sites for remediation...of locomotor activity and auditory startle reflex tests will be provided in the detailed technical report (in progress). Body Weights and Food...Olfactory Sensitization, Acoustic Startle, Prepulse Inhibition and Habituation, Total Locomotor Activity, Tail Flick Analgesia, and the Treadmill Test of

Vliv hipokampální aplikace Nr1/Nr2 antisense oligodeoxynukleotidů na expresi proteinů postsynaptické denzity a na prepulzní inhibici

Czech Academy of Sciences Publication Activity Database

Vrajová, M.; Klaschka, Jan; Tejkalová, H.; Bubeníková-Valešová, V.

2011-01-01

Roč. 15, Suppl. 2 (2011), s. 11-14 ISSN 1211-7579 R&D Projects: GA MŠk(CZ) 1M0517 Institutional research plan: CEZ:AV0Z10300504 Keywords : NMDA receptor * PSD proteins * antisense oligodeoxynucleotides for NMDA-NR1/NR2 subunits * prepulse inhibition Subject RIV: FL - Psychiatry, Sexuology http://www.tigis.cz/images/stories/psychiatrie/2011/s2/03_vrajova_cns_2-11.pdf

Profiles of VGF Peptides in the Rat Brain and Their Modulations after Phencyclidine Treatment

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Barbara Noli

2017-06-01

Full Text Available From the VGF precursor protein originate several low molecular weight peptides, whose distribution in the brain and blood circulation is not entirely known. Among the VGF peptides, those containing the N-terminus portion were altered in the cerebro-spinal fluid (CSF and hypothalamus of schizophrenia patients. “Hence, we aimed to better investigate the involvement of the VGF peptides in schizophrenia by studying their localization in the brain regions relevant for the disease, and revealing their possible modulations in response to certain neuronal alterations occurring in schizophrenia”. We produced antibodies against different VGF peptides encompassing the N-terminus, but also C-terminus-, TLQP-, GGGE- peptide sequences, and the so named NERP-3 and -4. These antibodies were used to carry out specific ELISA and immunolocalization studies while mass spectrometry (MS analysis was also performed to recognize the intact brain VGF fragments. We used a schizophrenia rat model, in which alterations in the prepulse inhibition (PPI of the acoustic startle response occurred after PCP treatment. In normal rats, all the VGF peptides studied were distributed in the brain areas examined including hypothalamus, prefrontal cortex, hippocampus, accumbens and amygdaloid nuclei and also in the plasma. By liquid chromatography-high resolution mass, we identified different intact VGF peptide fragments, including those encompassing the N-terminus and the NERPs. PCP treatment caused behavioral changes that closely mimic schizophrenia, estimated by us as a disruption of PPI of the acoustic startle response. The PCP treatment also induced selective changes in the VGF peptide levels within certain brain areas. Indeed, an increase in VGF C-terminus and TLQP peptides was revealed in the prefrontal cortex (p < 0.01 where they were localized within parvoalbumin and tyrosine hydroxylase (TH containing neurons, respectively. Conversely, in the nucleus accumbens, PCP

Dietary Inulin Fibers Prevent Proton-Pump Inhibitor (PPI)-Induced Hypocalcemia in Mice.

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Hess, Mark W; de Baaij, Jeroen H F; Gommers, Lisanne M M; Hoenderop, Joost G J; Bindels, René J M

2015-01-01

Proton-pump inhibitor-induced hypomagnesemia (PPIH) is the most recognized side effect of proton-pump inhibitors (PPIs). Additionally, PPIH is associated with hypocalcemia and hypokalemia. It is hypothesized that PPIs reduce epithelial proton secretion and thereby increase the pH in the colon, which may explain the reduced absorption of and Mg2+ and Ca2+. Fermentation of dietary oligofructose-enriched inulin fibers by the microflora leads to acidification of the intestinal lumen and by this enhances mineral uptake. This study aimed, therefore, to improve mineral absorption by application of dietary inulin to counteract PPIH. Here, C57BL/J6 mice were supplemented with omeprazole and/or inulin. Subsequently, Mg2+ and Ca2+ homeostasis was assessed by means of serum, urine and fecal electrolyte measurements. Moreover, the mRNA levels of magnesiotropic and calciotropic genes were examined in the large intestine and kidney by real-time PCR. Treatment with omeprazole significantly reduced serum Mg2+ and Ca2+ levels. However, concomitant addition of dietary inulin fibers normalized serum Ca2+ but not serum Mg2+ concentrations. Inulin abolished enhanced expression of Trpv6 and S100g in the colon by omeprazole. Additionally, intestinal and renal mRNA levels of the Trpm6 gene were reduced after inulin intake. This study suggests that dietary inulin counteracts reduced intestinal Ca2+ absorption upon PPI treatment. In contrast, inulin did not increase intestinal absorption of Mg2+ sufficiently to recover serum Mg2+. The clinical potential of dietary inulin treatment should be the subject of future studies.

Twice-daily dosing of esomeprazole effectively inhibits acid secretion in CYP2C19 rapid metabolisers compared with twice-daily omeprazole, rabeprazole or lansoprazole.

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Sahara, S; Sugimoto, M; Uotani, T; Ichikawa, H; Yamade, M; Iwaizumi, M; Yamada, T; Osawa, S; Sugimoto, K; Umemura, K; Miyajima, H; Furuta, T

2013-11-01

Twice-daily dosing of proton pump inhibitors (PPIs) is used to treat Helicobacter pylori or acid-related diseases, such as gastro-oesophageal reflux disease (GERD) refractory to standard dose of a PPI. Genetic polymorphisms of CYP2C19 are involved to different extents in the metabolism of four kinds of PPIs (omeprazole, lansoprazole, rabeprazole and esomeprazole) available in Japan. To compare acid-inhibitory effects of the four PPIs dosed twice daily in relation to CYP2C19 genotype. We performed 24-h pH monitoring studies on Day 7 of PPI treatment for 40 Japanese H. pylori-negative volunteers [15 CYP2C19 rapid metabolisers (RMs), 15 intermediate metabolisers (IMs) and 10 poor metabolisers (PMs)] using a randomised four-way crossover design: omeprazole 20 mg, esomeprazole 20 mg, lansoprazole 30 mg and rabeprazole 10 mg twice daily. Although median pH values with esomeprazole, omeprazole, lansoprazole and rabeprazole were 5.7 (3.5-7.2), 5.5 (2.4-7.2), 5.5 (3.7-7.3) and 5.2 (2.5-7.3), respectively (no statistically significant differences), CYP2C19 genotype-dependent differences were smaller for esomeprazole and rabeprazole compared with values for omeprazole and lansoprazole. In CYP2C19 RMs, the median pH with esomeprazole [5.4 (3.5-6.8)] was significantly higher than those with omeprazole [5.0 (2.4-5.9), P = 0.018], lansoprazole [4.7 (3.7-5.5), P = 0.017] or rabeprazole [4.8 (2.5-6.4), P = 0.002]. In IMs and PMs, the median pH was >5.0 independent of the PPI. In intermediate and rapid metabolisers of CYP2C19, PPIs dosed twice daily could attain sufficient acid suppression, while in CYP2C19 RMs, esomeprazole 20 mg twice daily caused the strongest inhibition of the four PPIs. Therefore, esomeprazole may be effective in Japanese population when dosed twice daily. © 2013 John Wiley & Sons Ltd.

Influence of Monomer Concentration on the Morphologies and Electrochemical Properties of PEDOT, PANI, and PPy Prepared from Aqueous Solution

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Shalini Kulandaivalu

2016-01-01

Full Text Available Poly(3,4-ethylenedioxyhiophene (PEDOT, polyaniline (PANI, and polypyrrole (PPy were prepared on indium tin oxide (ITO substrate via potentiostatic from aqueous solutions containing monomer and lithium perchlorate. The concentration of monomers was varied between 1 and 10 mM. The effects of monomer concentration on the polymers formation were investigated and compared by using Fourier transform infrared spectroscopy (FTIR, Raman spectroscopy, scanning electron microscopy (SEM, cyclic voltammetry (CV, and electrochemical impedance spectroscopy (EIS measurements. FTIR and Raman spectra showed no changes in the peaks upon the increment of the concentration. Based on the SEM images, the increment in monomer concentration gives significant effect on morphologies and eventually affects the electrochemical properties. PEDOT electrodeposited from 10 mM solution showed excellent electrochemical properties with the highest specific capacitance value of 12.8 mF/cm2.

Frequency discrimination in rats exposed to noise as juveniles

Czech Academy of Sciences Publication Activity Database

Šuta, Daniel; Rybalko, Natalia; Shen, D.W.; Popelář, Jiří; Poon, P. W. F.; Syka, Josef

2015-01-01

Roč. 144, may 15 (2015), s. 60-65 ISSN 0031-9384 R&D Projects: GA ČR(CZ) GCP303/11/J005; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378041 Keywords : auditory system * behavioral * critical period * development * noise exposure * prepulse inhibition * startle reflex Subject RIV: FH - Neurology Impact factor: 2.461, year: 2015

Age-related changes in the acoustic startle reflex in Fischer 344 and Long Evans rats

Czech Academy of Sciences Publication Activity Database

Rybalko, Natalia; Bureš, Zbyněk; Burianová, Jana; Popelář, Jiří; Poon, P. W. F.; Syka, Josef

2012-01-01

Roč. 47, č. 12 (2012), s. 966-973 ISSN 0531-5565 R&D Projects: GA ČR(CZ) GAP304/12/1342; GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GCP303/11/J005 Institutional research plan: CEZ:AV0Z50390512 Institutional support: RVO:68378041 Keywords : aging * acoustic startle response * prepulse inhibition Subject RIV: FH - Neurology Impact factor: 3.911, year: 2012

Sex-Dependent Psychoneuroendocrine Effects of THC and MDMA in an Animal Model of Adolescent Drug Consumption

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Llorente-Berzal, Alvaro; Puighermanal, Emma; Burokas, Aurelijus; Ozaita, Andrés; Maldonado, Rafael; Marco, Eva M.; Viveros, Maria-Paz

2013-01-01

Ecstasy is a drug that is usually consumed by young people at the weekends and frequently, in combination with cannabis. In the present study we have investigated the long-term effects of administering increasing doses of delta-9-tetrahydrocannabinol [THC; 2.5, 5, 10 mg/kg; i.p.] from postnatal day (pnd) 28 to 45, alone and/or in conjunction with 3,4-methylenedioxymethamphetamine [MDMA; two daily doses of 10 mg/kg every 5 days; s.c.] from pnd 30 to 45, in both male and female Wistar rats. When tested one day after the end of the pharmacological treatment (pnd 46), MDMA administration induced a reduction in directed exploration in the holeboard test and an increase in open-arm exploration in an elevated plus maze. In the long-term, cognitive functions in the novel object test were seen to be disrupted by THC administration to female but not male rats. In the prepulse inhibition test, MDMA-treated animals showed a decrease in prepulse inhibition at the most intense prepulse studied (80 dB), whereas in combination with THC it induced a similar decrease at 75 dB. THC decreased hippocampal Arc expression in both sexes, while in the frontal cortex this reduction was only evident in females. MDMA induced a reduction in ERK1/2 immunoreactivity in the frontal cortex of male but not female animals, and THC decreased prepro-orexin mRNA levels in the hypothalamus of males, although this effect was prevented when the animals also received MDMA. The results presented indicate that adolescent exposure to THC and/or MDMA induces long-term, sex-dependent psychophysiological alterations and they reveal functional interactions between the two drugs. PMID:24223797

Sex-dependent psychoneuroendocrine effects of THC and MDMA in an animal model of adolescent drug consumption.

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Alvaro Llorente-Berzal

Full Text Available Ecstasy is a drug that is usually consumed by young people at the weekends and frequently, in combination with cannabis. In the present study we have investigated the long-term effects of administering increasing doses of delta-9-tetrahydrocannabinol [THC; 2.5, 5, 10 mg/kg; i.p.] from postnatal day (pnd 28 to 45, alone and/or in conjunction with 3,4-methylenedioxymethamphetamine [MDMA; two daily doses of 10 mg/kg every 5 days; s.c.] from pnd 30 to 45, in both male and female Wistar rats. When tested one day after the end of the pharmacological treatment (pnd 46, MDMA administration induced a reduction in directed exploration in the holeboard test and an increase in open-arm exploration in an elevated plus maze. In the long-term, cognitive functions in the novel object test were seen to be disrupted by THC administration to female but not male rats. In the prepulse inhibition test, MDMA-treated animals showed a decrease in prepulse inhibition at the most intense prepulse studied (80 dB, whereas in combination with THC it induced a similar decrease at 75 dB. THC decreased hippocampal Arc expression in both sexes, while in the frontal cortex this reduction was only evident in females. MDMA induced a reduction in ERK1/2 immunoreactivity in the frontal cortex of male but not female animals, and THC decreased prepro-orexin mRNA levels in the hypothalamus of males, although this effect was prevented when the animals also received MDMA. The results presented indicate that adolescent exposure to THC and/or MDMA induces long-term, sex-dependent psychophysiological alterations and they reveal functional interactions between the two drugs.

Experimental analysis of R134a flow boiling inside a 5 PPI copper foam

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Diani, A.; Mancin, S.; Rossetto, L.

2014-04-01

Heat dissipation is one of the most important issues for the reliability of electronic equipment. Boiling can be a very efficient heat transfer mechanism when used to face with the electronic technology needs of efficient and compact heat sinks. Recently, cellular structured materials both stochastic and periodic, particularly open cell metal foams, have been proposed as possible enhanced surfaces to lower the junction temperatures at high heat fluxes. Up today, most of the research on metal foams only regards single phase flow, whereas the two phase flow is still almost unexplored. This paper presents an experimental study on the heat transfer of R134a during flow boiling inside a 5 PPI (Pores Per linear Inch) copper foam, which is 5 mm high, 10 mm wide and 200 mm long, and it is brazed on a 10 mm thick copper plate. The experimental measurements were carried out by imposing three different heat fluxes (50, 75, and 100 kW m-2) and by varying the refrigerant mass velocity between 50 and 200 kg m-2 s-1 and the vapour quality from 0.2 to 0.90, at constant saturation temperature (30°C). The effects of the refrigerant mass flow rate, heat flux and vapour quality on the heat transfer coefficient, dry out phenomenon, and pressure drop are studied.

Brief postnatal exposure to phenobarbital impairs passive avoidance learning and sensorimotor gating in rats.

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Gutherz, Samuel B; Kulick, Catherine V; Soper, Colin; Kondratyev, Alexei; Gale, Karen; Forcelli, Patrick A

2014-08-01

Phenobarbital is the most commonly utilized drug for the treatment of neonatal seizures. However, mounting preclinical evidence suggests that even brief exposure to phenobarbital in the neonatal period can induce neuronal apoptosis, alterations in synaptic development, and long-lasting changes in behavioral functions. In the present report, we treated neonatal rat pups with phenobarbital and evaluated behavior in adulthood. Pups were treated initially with a loading dose (80 mg/kg) on postnatal day (P)7 and with a lower dose (40 mg/kg) on P8 and P9. We examined sensorimotor gating (prepulse inhibition), passive avoidance, and conditioned place preference for cocaine when the animals reached adulthood. Consistent with our previous reports, we found that three days of neonatal exposure to phenobarbital significantly impaired prepulse inhibition compared with vehicle-exposed control animals. Using a step-though passive avoidance paradigm, we found that animals exposed to phenobarbital as neonates and tested as adults showed significant deficits in passive avoidance retention compared with matched controls, indicating impairment in associative memory and/or recall. Finally, we examined place preference conditioning in response to cocaine. Phenobarbital exposure did not alter the normal conditioned place preference associated with cocaine exposure. Our findings expand the profile of behavioral toxicity induced by phenobarbital. Copyright © 2014 Elsevier Inc. All rights reserved.

Brief postnatal exposure to phenobarbital impairs passive-avoidance learning and sensorimotor gating in rats

Science.gov (United States)

Gutherz, Samuel B.; Kulick, Catherine V.; Soper, Colin; Kondratyev, Alexei; Gale, Karen; Forcelli, Patrick A.

2014-01-01

Phenobarbital is the most commonly utilized drug for the treatment of neonatal seizures. However, mounting preclinical evidence suggests that even brief exposure to phenobarbital in the neonatal period can induce neuronal apoptosis, alterations in synaptic development, and long-lasting changes in behavioral functions. In the present report, we treated neonatal rat pups with phenobarbital and evaluated behavior in adulthood. Pups were treated initially with a loading dose (80mg/kg) on postnatal day (P)7 and with a lower dose (40 mg/kg) on P8 and P9. We examined sensorimotor gating (prepulse inhibition), passive avoidance, and conditioned place preference to cocaine when the animals reached adulthood. Consistent with our previous reports, we found that three days of neonatal exposure to phenobarbital significantly impaired prepulse inhibition as compared to vehicle-exposed control animals. Using a step-though passive avoidance paradigm, we found that animals exposed to phenobarbital as neonates and tested as adults showed significant deficits in passive avoidance retention as compared to matched controls, indicating impairment in associative memory and/or recall. Finally, we examined place preference conditioning in response to cocaine. Phenobarbital exposure did not alter the normal conditioned place preference associated with cocaine exposure. Our findings expand the profile of behavioral toxicity induced by phenobarbital. PMID:25112558

Intersystem-crossing and phosphorescence rates in fac-Ir{sup III}(ppy){sub 3}: A theoretical study involving multi-reference configuration interaction wavefunctions

Energy Technology Data Exchange (ETDEWEB)

Kleinschmidt, Martin; Marian, Christel M., E-mail: Christel.Marian@hhu.de [Institute of Theoretical and Computational Chemistry, Heinrich-Heine-University Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf (Germany); Wüllen, Christoph van [Fachbereich Chemie and Forschungszentrum OPTIMAS, Technical University of Kaiserslautern, Erwin-Schrödinger-Straße 52, 67663 Kaiserslautern (Germany)

2015-03-07

We have employed combined density functional theory and multi-reference configuration interaction methods including spin–orbit coupling (SOC) effects to investigate the photophysics of the green phosphorescent emitter fac-tris-(2-phenylpyridine)iridium (fac-Ir(ppy){sub 3}). A critical evaluation of our quantum chemical approaches shows that a perturbational treatment of SOC is the method of choice for computing the UV/Vis spectrum of this heavy transition metal complex while multi-reference spin–orbit configuration interaction is preferable for calculating the phosphorescence rates. The particular choice of the spin–orbit interaction operator is found to be of minor importance. Intersystem crossing (ISC) rates have been determined by Fourier transformation of the time correlation function of the transition including Dushinsky rotations. In the electronic ground state, fac-Ir(ppy){sub 3} is C{sub 3} symmetric. The calculated UV/Vis spectrum is in excellent agreement with experiment. The effect of SOC is particularly pronounced for the metal-to-ligand charge transfer (MLCT) band in the visible region of the absorption spectrum which does not only extend its spectral onset towards longer wavelengths but also experiences a blue shift of its maximum. Pseudo-Jahn-Teller interaction leads to asymmetric coordinate displacements in the lowest MLCT states. Substantial electronic SOC and a small energy gap make ISC an ultrafast process in fac-Ir(ppy){sub 3}. For the S{sub 1}↝T{sub 1} non-radiative transition, we compute a rate constant of k{sub ISC} = 6.9 × 10{sup 12} s{sup −1} which exceeds the rate constant of radiative decay to the electronic ground state by more than six orders of magnitude, in agreement with the experimental observation of a subpicosecond ISC process and a triplet quantum yield close to unity. As a consequence of the geometric distortion in the T{sub 1} state, the T{sub 1} → S{sub 0} transition densities are localized on one of the

Pharmacokinetics and pharmacodynamics of the proton pump inhibitors.

Science.gov (United States)

Shin, Jai Moo; Kim, Nayoung

2013-01-01

Proton pump inhibitor (PPI) is a prodrug which is activated by acid. Activated PPI binds covalently to the gastric H(+), K(+)-ATPase via disulfide bond. Cys813 is the primary site responsible for the inhibition of acid pump enzyme, where PPIs bind. Omeprazole was the first PPI introduced in market, followed by pantoprazole, lansoprazole and rabeprazole. Though these PPIs share the core structures benzimidazole and pyridine, their pharmacokinetics and pharmacodynamics are a little different. Several factors must be considered in understanding the pharmacodynamics of PPIs, including: accumulation of PPI in the parietal cell, the proportion of the pump enzyme located at the canaliculus, de novo synthesis of new pump enzyme, metabolism of PPI, amounts of covalent binding of PPI in the parietal cell, and the stability of PPI binding. PPIs have about 1hour of elimination half-life. Area under the plasmic concentration curve and the intragastric pH profile are very good indicators for evaluating PPI efficacy. Though CYP2C19 and CYP3A4 polymorphism are major components of PPI metabolism, the pharmacokinetics and pharmacodynamics of racemic mixture of PPIs depend on the CYP2C19 genotype status. S-omeprazole is relatively insensitive to CYP2C19, so better control of the intragastric pH is achieved. Similarly, R-lansoprazole was developed in order to increase the drug activity. Delayed-release formulation resulted in a longer duration of effective concentration of R-lansoprazole in blood, in addition to metabolic advantage. Thus, dexlansoprazole showed best control of the intragastric pH among the present PPIs. Overall, PPIs made significant progress in the management of acid-related diseases and improved health-related quality of life.

A metal-based inhibitor of NEDD8-activating enzyme.

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Hai-Jing Zhong

Full Text Available A cyclometallated rhodium(III complex [Rh(ppy(2(dppz](+ (1 (where ppy=2-phenylpyridine and dppz=dipyrido[3,2-a:2',3'-c]phenazine dipyridophenazine has been prepared and identified as an inhibitor of NEDD8-activating enzyme (NAE. The complex inhibited NAE activity in cell-free and cell-based assays, and suppressed the CRL-regulated substrate degradation and NF-κB activation in human cancer cells with potency comparable to known NAE inhibitor MLN4924. Molecular modeling analysis suggested that the overall binding mode of 1 within the binding pocket of the APPBP1/UBA3 heterodimer resembled that for MLN4924. Complex 1 is the first metal complex reported to suppress the NEDDylation pathway via inhibition of the NEDD8-activating enzyme.

Emotional Contagion is not Altered in Mice Prenatally Exposed to Poly (I:C) on Gestational Day 9.

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Gonzalez-Liencres, Cristina; Juckel, Georg; Esslinger, Manuela; Wachholz, Simone; Manitz, Marie-Pierre; Brüne, Martin; Friebe, Astrid

2016-01-01

Prenatal immune activation has been associated with increased risk of developing schizophrenia. The polyinosinic-polycytidylic acid (Poly(I:C)) mouse model replicates some of the endophenotype characteristic of this disorder but the social deficits observed in schizophrenia patients have not been well studied in this model. Therefore we aimed to investigate social behavior, in particular emotional contagion for pain, in this mouse model. We injected pregnant mouse dams with Poly(I:C) or saline (control) on gestation day 9 (GD9) and we evaluated their offspring in the pre-pulse inhibition (PPI) test at age 50-55 days old to confirm the reliability of our model. Mice were then evaluated in an emotional contagion test immediately followed by the light/dark test to explore post-test anxiety-like behavior at 10 weeks of age. In the emotional contagion test, an observer (prenatally exposed to Poly(I:C) or to saline) witnessed a familiar wild-type (WT) mouse (demonstrator) receiving electric foot shocks. Our results replicate the sensory gating impairments in the Poly(I:C) offspring but we only observed minor group differences in the social tasks. One of the differences we found was that demonstrators deposited fewer feces in the presence of control observers than of observers prenatally exposed to Poly(I:C), which we suggest could be due to the observers' behavior. We discuss the findings in the context of age, sex and day of prenatal injection, suggesting that Poly(I:C) on GD9 may be a valuable tool to assess other symptoms or symptom clusters of schizophrenia but perhaps not comprising the social domain.

Effects of environmental enrichment on anxiety-like behavior, sociability, sensory gating, and spatial learning in male and female C57BL/6J mice.

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Hendershott, Taylor R; Cronin, Marie E; Langella, Stephanie; McGuinness, Patrick S; Basu, Alo C

2016-11-01

The influence of housing on cognition and emotional regulation in mice presents a problem for the study of genetic and environmental risk factors for neuropsychiatric disorders: standard laboratory housing may result in low levels of cognitive function or altered levels of anxiety that leave little room for assessment of deleterious effects of experimental manipulations. The use of enriched environment (EE) may allow for the measurement of a wider range of performance in cognitive domains. Cognitive and behavioral effects of EE in male mice have not been widely reproduced, perhaps due to variability in the application of enrichment protocols, and the effects of EE in female mice have not been widely studied. We have developed an EE protocol using common laboratory equipment that, without a running wheel for exercise, results in significant cognitive and behavioral effects relative to standard laboratory housing conditions. We compared male and female wild-type C57BL/6J mice reared from weaning age in an EE to those reared in a standard environment (SE), using common measures of anxiety-like behavior, sensory gating, sociability, and spatial learning and memory. Sex was a significant factor in relevant elevated plus maze (EPM) measures, and bordered on significance in a social interaction (SI) assay. Effects of EE on anxiety-like behavior and sociability were indicative of a general increase in exploratory activity. In male and female mice, EE resulted in reduced prepulse inhibition (PPI) of the acoustic startle response, and enhanced spatial learning and use of spatially precise strategies in a Morris water maze task. Copyright © 2016 Elsevier B.V. All rights reserved.

Antioxidant Treatment with N-acetyl Cysteine Prevents the Development of Cognitive and Social Behavioral Deficits that Result from Perinatal Ketamine Treatment

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Aarron Phensy

2017-06-01

Full Text Available Alterations of the normal redox state can be found in all stages of schizophrenia, suggesting a key role for oxidative stress in the etiology and maintenance of the disease. Pharmacological blockade of N-methyl-D-aspartic acid (NMDA receptors can disrupt natural antioxidant defense systems and induce schizophrenia-like behaviors in animals and healthy human subjects. Perinatal administration of the NMDA receptor (NMDAR antagonist ketamine produces persistent behavioral deficits in adult mice which mimic a range of positive, negative, and cognitive symptoms that characterize schizophrenia. Here we tested whether antioxidant treatment with the glutathione (GSH precursor N-acetyl-cysteine (NAC can prevent the development of these behavioral deficits. On postnatal days (PND 7, 9 and 11, we treated mice with subanesthetic doses (30 mg/kg of ketamine or saline. Two groups (either ketamine or saline treated also received NAC throughout development. In adult animals (PND 70–120 we then assessed behavioral alterations in a battery of cognitive and psychomotor tasks. Ketamine-treated animals showed deficits in a task of cognitive flexibility, abnormal patterns of spontaneous alternation, deficits in novel-object recognition, as well as social interaction. Developmental ketamine treatment also induced behavioral stereotypy in response to an acute amphetamine challenge, and it impaired sensorimotor gating, measured as reduced prepulse inhibition (PPI of the startle response. All of these behavioral abnormalities were either prevented or strongly ameliorated by NAC co-treatment. These results suggest that oxidative stress is a major factor for the development of the ketamine-induced behavioral dysfunctions, and that restoring oxidative balance during the prodromal stage of schizophrenia might be able to ameliorate the development of several major symptoms of the disease.

Overexpression of transmembrane protein 168 in the mouse nucleus accumbens induces anxiety and sensorimotor gating deficit.

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Kequan Fu

Full Text Available Transmembrane protein 168 (TMEM168 comprises 697 amino acid residues, including some putative transmembrane domains. It is reported that TMEM168 controls methamphetamine (METH dependence in the nucleus accumbens (NAc of mice. Moreover, a strong link between METH dependence-induced adaptive changes in the brain and mood disorders has been evaluated. In the present study, we investigated the effects of accumbal TMEM168 in a battery of behavioral paradigms. The adeno-associated virus (AAV Tmem168 vector was injected into the NAc of C57BL/6J mice (NAc-TMEM mice. Subsequently, the accumbal TMEM168 mRNA was increased approximately by seven-fold when compared with the NAc-Mock mice (controls. The NAc-TMEM mice reported no change in the locomotor activity, cognitive ability, social interaction, and depression-like behaviors; however, TMEM168 overexpression enhanced anxiety in the elevated-plus maze and light/dark box test. The increased anxiety was reversed by pretreatment with the antianxiety drug diazepam (0.3 mg/kg i.p.. Moreover, the NAc-TMEM mice exhibited decreased prepulse inhibition (PPI in the startle response test, and the induced schizophrenia-like behavior was reversed by pretreatment with the antipsychotic drug risperidone (0.01 mg/kg i.p.. Furthermore, accumbal TMEM168 overexpression decreased the basal levels of extracellular GABA in the NAc and the high K+ (100 mM-stimulated GABA elevation; however, the total contents of GABA in the NAc remained unaffected. These results suggest that the TMEM168-regulated GABAergic neuronal system in the NAc might become a novel target while studying the etiology of anxiety and sensorimotor gating deficits.

AVN-492, A Novel Highly Selective 5-HT6R Antagonist: Preclinical Evaluation.

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Ivachtchenko, Alexandre V; Okun, Ilya; Aladinskiy, Vladimir; Ivanenkov, Yan; Koryakova, Angela; Karapetyan, Ruben; Mitkin, Oleg; Salimov, Ramiz; Ivashchenko, Andrey

2017-01-01

Discovery of 5-HT6 receptor subtype and its exclusive localization within the central nervous system led to extensive investigations of its role in Alzheimer's disease, schizophrenia, and obesity. In the present study, we present preclinical evaluation of a novel highly-potent and highly-selective 5-HT6R antagonist, AVN-492. The affinity of AVN-492 to bind to 5-HT6R (Ki = 91 pM) was more than three orders of magnitude higher than that to bind to the only other target, 5-HT2BR, (Ki = 170 nM). Thus, the compound displayed great 5-HT6R selectivity against all other serotonin receptor subtypes, and is extremely specific against any other receptors such as adrenergic, GABAergic, dopaminergic, histaminergic, etc. AVN-492 demonstrates good in vitro and in vivo ADME profile with high oral bioavailability and good brain permeability in rodents. In behavioral tests, AVN-492 shows anxiolytic effect in elevated plus-maze model, prevents an apomorphine-induced disruption of startle pre-pulse inhibition (the PPI model) and reverses a scopolamine- and MK-801-induced memory deficit in passive avoidance model. No anti-obesity effect of AVN-492 was found in a murine model. The data presented here strongly indicate that due to its high oral bioavailability, extremely high selectivity, and potency to block the 5-HT6 receptor, AVN-492 is a very promising tool for evaluating the role the 5-HT6 receptor might play in cognitive and neurodegenerative impairments. AVN-492 is an excellent drug candidate to be tested for treatment of such diseases, and is currently being tested in Phase I trials.

Effects of postnatal anoxia on striatal dopamine metabolism and prepulse inhibition in rats

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Sandager-Nielsen, Karin; Andersen, Maibritt B; Sager, Thomas N

2004-01-01

(DOPAC) and homovanillic acid (HVA) concentrations. Furthermore, in the anoxic group only, striatal HVA concentrations were negatively correlated to prefrontal cortical N-acetylaspartate (NAA) levels. Similar findings of distorted prefrontal-subcortical interactions have recently been reported...

Electrochemiluminescence behavior of AgNCs and its application in immunosensors based on PANI/PPy-Ag dendrite-modified electrode.

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Zhang, Lina; Wang, Yanhu; Shen, Lei; Yu, Jinghua; Ge, Shenguang; Yan, Mei

2017-07-10

In this study, hyperbranched polyethyleneimine-protected silver nanoclusters (hPEI-AgNCs) with excellent electrochemiluminescence (ECL) emission in the presence of coreactant K 2 S 2 O 8 were prepared by chemical reduction of silver ions (silver nitrate) coordinated with dendrigraft polymer, and successfully used for the construction of an ECL immunosensor. Polyaniline (PANI)/polypyrrole (PPy)-silver (Ag) dendrites with good electrical conductivity and biocompatibility were electropolymerized on the surface of indium tin oxide (ITO) electrode as carriers. Porous ZnO sphere-loaded hPEI-AgNCs-induced signal amplification strategies were integrated exquisitely and applied sufficiently. Taking carcinoembryonic antigen (CEA) as an example, under optimal conditions, the CEA concentration was determined to be in the range of 10 -3 ng mL -1 -100 ng mL -1 and with a detection limit of 0.4 pg mL -1 using this method; it exhibited excellent selectivity, high stability, and acceptable fabrication reproducibility. It was anticipated that hPEI-AgNCs would have promising applications in green, selective, and sensitive detection of target analytes in the future.

Studying the Polypropylenimine-G2 (PPI-G2 Dendrimer Performance in Removal of Escherichia coli, Proteus mirabilis, Bacillus subtilis and Staphylococcus aureus from Aqueous Solution

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Hasan Izanloo

2015-09-01

Full Text Available Abstract Background: Dendrimers are a subset of branched structures that have certain structural order. The aim of this study was to investigate the performance of Polypropylenimine-G2 (PPI-G2 dendrimers in removal of Escherichia coli, Proteus mirabilis, Bacillus subtilis and Staphylococcus aureus from aqueous solution. Materials and Methods: In this experimental study, initially dilution of 103 CFU/ml was prepared from each strain of bacteria. Then, different concentrations of dendrimers (0.5, 5, 50 and 500 µg/ml was added to water. In order to determine the efficiency of dendrimers in removal of bacteria, samples were taken at different times (0, 10, 20, 30, 40, 50 and 60 min and were cultured on nutrient agar medium. Samples were incubated for 24 hours at 37 ° C and then the number of colonies was counted. Results: By the increasment of dendrimer concentration and contact time, the number of bacteria in aqueous solution decreased. In times of 40, 50 and 60 minutes, and the concentrations of 50 and 500 µg/ml, all kinds of bacteria in aqueous solution were removed. 0.5 µg/ml of dendrimer concentration had not effect in reducing the number of Escherichia coli and Proteus mirabilis. The effect of dendrimer on gram-negative bacteria was weaker than gram-positive bacteria. Conclusion: Results of this study indicated that PPI-G2 dendrimer is able to remove Escherichia coli, Proteus mirabilis, Staphylococcus aureus and Bacillus subtilis in aqueous solution. However, using dendrimers can be considered as a new approach for drinking water disinfection but it requires further wide range studies.

Arctigenin ameliorates inflammation in vitro and in vivo by inhibiting the PI3K/AKT pathway and polarizing M1 macrophages to M2-like macrophages.

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Hyam, Supriya R; Lee, In-Ah; Gu, Wan; Kim, Kyung-Ah; Jeong, Jin-Ju; Jang, Se-Eun; Han, Myung Joo; Kim, Dong-Hyun

2013-05-15

Seeds of Arctium lappa, containing arctigenin and its glycoside arctiin as main constituents, have been used as a diuretic, anti-inflammatory and detoxifying agent in Chinese traditional medicine. In our preliminary study, arctigenin inhibited IKKβ and NF-κB activation in peptidoglycan (PGN)- or lipopolysaccharide (LPS)-induced peritoneal macrophages. To understand the anti-inflammatory effect of arctigenin, we investigated its anti-inflammatory effect in LPS-stimulated peritoneal macrophages and on LPS-induced systemic inflammation as well as 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Arctigenin inhibited LPS-increased IL-1β, IL-6 and TNF-α expression in LPS-stimulated peritoneal macrophages, but increased LPS-reduced IL-10 and CD204 expression. Arctigenin inhibited LPS-induced PI3K, AKT and IKKβ phosphorylation, but did not suppress LPS-induced IRAK-1 phosphorylation. However, arctigenin did not inhibit NF-κB activation in LPS-stimulated PI3K siRNA-treated peritoneal macrophages. Arctigenin suppressed the binding of p-PI3K antibody and the nucleus translocation of NF-κB p65 in LPS-stimulated peritoneal macrophages. Arctigenin suppressed blood IL-1β and TNF-α level in mice systemically inflamed by intraperitoneal injection of LPS. Arctigenin also inhibited colon shortening, macroscopic scores and myeloperoxidase activity in TNBS-induced colitic mice. Arctigenin inhibited TNBS-induced IL-1β, TNF-α and IL-6 expression, as well as PI3K, AKT and IKKβ phosphorylation and NF-κB activation in mice, but increased IL-10 and CD204 expression. However, it did not affect IRAK-1 phosphorylation. Based on these findings, arctigenin may ameliorate inflammatory diseases, such as colitis, by inhibiting PI3K and polarizing M1 macrophages to M2-like macrophages. Copyright © 2013 Elsevier B.V. All rights reserved.

Extracellular acidosis and very low [Na+ ] inhibit NBCn1- and NHE1-mediated net acid extrusion from mouse vascular smooth muscle cells.

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Bonde, L; Boedtkjer, E

2017-10-01

The electroneutral Na + , HCO3- cotransporter NBCn1 and Na + /H + exchanger NHE1 regulate acid-base balance in vascular smooth muscle cells (VSMCs) and modify artery function and structure. Pathological conditions - notably ischaemia - can dramatically perturb intracellular (i) and extracellular (o) pH and [Na + ]. We examined effects of low [Na + ] o and pH o on NBCn1 and NHE1 activity in VSMCs of small arteries. We measured pH i by 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein-based fluorescence microscopy of mouse mesenteric arteries and induced intracellular acidification by NH4+ prepulse technique. NBCn1 activity - defined as Na + -dependent, amiloride-insensitive net base uptake with CO 2 /HCO3- present - was inhibited equally when pH o decreased from 7.4 (22 mm HCO3-/5% CO 2 ) by metabolic (pH o 7.1/11 mm HCO3-: 22 ± 8%; pH o 6.8/5.5 mm HCO3-: 61 ± 7%) or respiratory (pH o 7.1/10% CO 2 : 35 ± 11%; pH o 6.8/20% CO 2 : 56 ± 7%) acidosis. Extracellular acidosis more prominently inhibited NHE1 activity - defined as Na + -dependent net acid extrusion without CO 2 /HCO3- present - at both pH o 7.1 (45 ± 9%) and 6.8 (85 ± 5%). Independently of pH o , lowering [Na + ] o from 140 to 70 mm reduced NBCn1 and NHE1 activity respiratory (ΔpH i /ΔpH o  = 71 ± 4%) than metabolic (ΔpH i /ΔpH o  = 30 ± 7%) acidosis. Extracellular acidification inhibits NBCn1 and NHE1 activity in VSMCs. NBCn1 is equivalently inhibited when pCO 2 is raised or [HCO3-] o decreased. Lowering [Na + ] o inhibits NBCn1 and NHE1 markedly only below the typical physiological and pathophysiological range. We propose that inhibition of Na + -dependent net acid extrusion at low pH o protects against cellular Na + overload at the cost of intracellular acidification. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Anticancer effects of kaempferol in A375 human malignant melanoma cells are mediated via induction of apoptosis, cell cycle arrest, inhibition of cell migration and downregulation of m-TOR/PI3K/AKT pathway.

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Yang, Jia; Xiao, Peng; Sun, Jiaming; Guo, Liang

2018-01-01

Melanoma is an aggressive form of human cancer with limited treatment options currently available. The present study was aimed to evaluate the anticancer activity of kaempferol (KAM) against the human malignant melanoma A375 cell line along with evaluation of its effects on apoptosis, cell cycle, cell migration and m-TOR/PI3K/AKT pathway. Effects on cell viability were assessed by MTT assay while clonogenic assay measured the effects of KAM on colony formation. Annexin V assay evaluated the apoptotic effects of KAM in these cells using flow cytometry. Effects on cell cycle were determined by using flow cytometry with propidium iodide (PI) as probe. The effects of KAM on m-TOR/ PI3K/AKT signalling pathway were evaluated by western blot assay. MTT assay indicated that KAM exhibits a significant anticancer activity against A375 cells with an IC50 of 20 μM. These antiproliferative effects of KAM were also supported by the colony formation assay wherein KAM reduced the colony formation in a dose-dependent manner. The anticancer effect of KAM was found to be due to the initiation of apoptosis in human malignant melanoma A375 cells. Additionally, KAM also exhibited the capacity to trigger G2/M cell cycle arrest and to inhibit the cell migratory potential of A375 cells. KAM caused significant downregulation of m-TOR, phosphorylated (p) m-TOR, PI3K, p-PI3K and Akt protein levels in A375 malignantmelanoma cells. KAM exerts potent anticancer effects via induction of apoptosis, G2/M cell cycle arrest, cell migration inhibition and downregulation of m-TOR, pm-TOR, PI3K, p-PI3K and Akt protein levels.

A new strategy to inhibit the excision reaction catalysed by HIV-1 reverse transcriptase: compounds that compete with the template–primer

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Cruchaga, Carlos; Anso, Elena; Font, María; Martino, Virginia S.; Rouzaut, Ana; Martinez-Irujo, Juan J.

2007-01-01

Inhibitors of the excision reaction catalysed by HIV-1 RT (reverse transcriptase) represent a promising approach in the fight against HIV, because these molecules would interfere with the main mechanism of resistance of this enzyme towards chain-terminating nucleotides. Only a limited number of compounds have been demonstrated to inhibit this reaction to date, including NNRTIs (non-nucleoside RT inhibitors) and certain pyrophosphate analogues. We have found previously that 2GP (2-O-galloylpunicalin), an antiviral compound extracted from the leaves of Terminalia triflora, was able to inhibit both the RT and the RNase H activities of HIV-1 RT without affecting cell proliferation or viability. In the present study, we show that 2GP also inhibited the ATP- and PPi-dependent phosphorolysis catalysed by wild-type and AZT (3′-azido-3′-deoxythymidine)-resistant enzymes at sub-micromolar concentrations. Kinetic and direct-binding analysis showed that 2GP was a non-competitive inhibitor against the nucleotide substrate, whereas it competed with the binding of RT to the template–primer (Kd=85 nM). As expected from its mechanism of action, 2GP was active against mutations conferring resistance to NNRTIs and AZT. The combination of AZT with 2GP was highly synergistic when tested in the presence of pyrophosphate, indicating that the inhibition of RT-catalysed phosphorolysis was responsible for the synergy found. Although other RT inhibitors that compete with the template–primer have been described, this is the first demonstration that these compounds can be used to block the excision of chain terminating nucleotides, providing a rationale for their combination with nucleoside analogues. PMID:17355225

Experimental evidence for the involvement of PDLIM5 in mood disorders in hetero knockout mice.

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Yasue Horiuchi

Full Text Available BACKGROUND: Reports indicate that PDLIM5 is involved in mood disorders. The PDLIM5 (PDZ and LIM domain 5 gene has been genetically associated with mood disorders; it's expression is upregulated in the postmortem brains of patients with bipolar disorder and downregulated in the peripheral lymphocytes of patients with major depression. Acute and chronic methamphetamine (METH administration may model mania and the evolution of mania into psychotic mania or schizophrenia-like behavioral changes, respectively. METHODS: To address whether the downregulation of PDLIM5 protects against manic symptoms and cause susceptibility to depressive symptoms, we evaluated the effects of reduced Pdlim5 levels on acute and chronic METH-induced locomotor hyperactivity, prepulse inhibition, and forced swimming by using Pdlim5 hetero knockout (KO mice. RESULTS: The homozygous KO of Pdlim5 is embryonic lethal. The effects of METH administration on locomotor hyperactivity and the impairment of prepulse inhibition were lower in Pdlim5 hetero KO mice than in wild-type mice. The transient inhibition of PDLIM5 (achieved by blocking the translocation of protein kinase C epsilon before the METH challenge had a similar effect on behavior. Pdlim5 hetero KO mice showed increased immobility time in the forced swimming test, which was diminished after the chronic administration of imipramine. Chronic METH treatment increased, whereas chronic haloperidol treatment decreased, Pdlim5 mRNA levels in the prefrontal cortex. Imipramine increased Pdlim5 mRNA levels in the hippocampus. CONCLUSION: These findings are partially compatible with reported observations in humans, indicating that PDLIM5 is involved in psychiatric disorders, including mood disorders.

Novel Technology for Protein-Protein Interaction-based Targeted Drug Discovery

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Jung Me Hwang

2011-12-01

Full Text Available We have developed a simple but highly efficient in-cell protein-protein interaction (PPI discovery system based on the translocation properties of protein kinase C- and its C1a domain in live cells. This system allows the visual detection of trimeric and dimeric protein interactions including cytosolic, nuclear, and/or membrane proteins with their cognate ligands. In addition, this system can be used to identify pharmacological small compounds that inhibit specific PPIs. These properties make this PPI system an attractive tool for screening drug candidates and mapping the protein interactome.

Involving seldom-heard groups in a PPI process to inform the design of a proposed trial on the use of probiotics to prevent preterm birth: a case study.

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Rayment, Juliet; Lanlehin, Rosemary; McCourt, Christine; Husain, Shahid M

2017-01-01

When designing clinical trials it is important to involve members of the public, who can provide a view on what may encourage or prevent people participating and on what matters to them. This is known as Public and Patient Involvement (PPI). People from minority ethnic groups are often less likely to take part in clinical trials, but it is important to ensure they are able to participate fully so that health research and its findings are relevant to a wide population. We are preparing to conduct a randomised controlled trial (RCT) to test whether taking probiotic capsules can play a role in preventing preterm birth. Women from some minority ethnic groups, for example women from West Africa, and those who are from low-income groups are more likely to suffer preterm births. Preterm birth can lead to extra costs to health services and psychosocial costs for families. In this article we describe how we engaged women in discussion about the design of the planned trial, and how we aim to use our findings to ensure the trial is workable and beneficial to women, as well as to further engage service users in the future development of the trial. Four socially and ethnically diverse groups of women in East London took part in discussions about the trial and contributed their ideas and concerns. These discussions have helped to inform and improve the design of a small practice or 'pilot' trial to test the recruitment in a 'real life' setting, as well as encourage further PPI involvement for the future full-scale trial. Background Patient and public involvement (PPI) is an important tool in approaching research challenges. However, involvement of socially and ethnically diverse populations remains limited and practitioners need effective methods of involving a broad section of the population in planning and designing research. Methods In preparation for the development of a pilot randomised controlled trial (RCT) on the use of probiotics to prevent preterm birth, we conducted a

Pharmacokinetic, Ambulatory, and Hyperthermic Effects of 3,4-Methylenedioxy-N-Methylcathinone (Methylone in Rats

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Kristýna Štefková

2017-11-01

Full Text Available Methylone (3,4-methylenedioxy-N-methylcathinone is a synthetic cathinone analog of the recreational drug ecstasy. Although it is marketed to recreational users as relatively safe, fatalities due to hyperthermia, serotonin syndrome, and multi-organ system failure have been reported. Since psychopharmacological data remain scarce, we have focused our research on pharmacokinetics, and on a detailed evaluation of temporal effects of methylone and its metabolite nor-methylone on behavior and body temperature in rats. Methylone [5, 10, 20, and 40 mg/kg subcutaneously (s.c.] and nor-methylone (10 mg/kg s.c. were used in adolescent male Wistar rats across three behavioral/physiological procedures and in two temporal windows from administration (15 and 60 min in order to test: locomotor effects in the open field, sensorimotor gating in the test of prepulse inhibition (PPI, and effects on rectal temperature in individually and group-housed rats. Serum and brain pharmacokinetics after 10 mg/kg s.c. over 8 h were analyzed using liquid chromatography mass spectrometry. Serum and brain levels of methylone and nor-methylone peaked at 30 min after administration, both drugs readily penetrated the brain with serum: brain ratio 1:7.97. Methylone dose-dependently increased overall locomotion. It also decrease the amount of time spent in the center of open field arena in dose 20 mg/kg and additionally this dose induced stereotyped circling around the arena walls. The maximum of effects corresponded to the peak of its brain concentrations. Nor-methylone had approximately the same behavioral potency. Methylone also has weak potency to disturb PPI. Behavioral testing was not performed with 40 mg/kg, because it was surprisingly lethal to some animals. Methylone 10 and 20 mg/kg s.c. induced hyperthermic reaction which was more pronounced in group-housed condition relative to individually housed rats. To conclude, methylone increased exploration and

Human iPSC Glial Mouse Chimeras Reveal Glial Contributions to Schizophrenia

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Windrem, Martha S.; Osipovitch, Mikhail; Liu, Zhengshan

2017-01-01

with childhood-onset SCZ. After neonatal implantation into myelin-deficient shiverer mice, SCZ GPCs showed premature migration into the cortex, leading to reduced white matter expansion and hypomyelination relative to controls. The SCZ glial chimeras also showed delayed astrocytic differentiation and abnormal...... astrocytic morphologies. When established in myelin wild-type hosts, SCZ glial mice showed reduced prepulse inhibition and abnormal behavior, including excessive anxiety, antisocial traits, and disturbed sleep. RNA-seq of cultured SCZ human glial progenitor cells (hGPCs) revealed disrupted glial...

Cyclosporine A-sensitive, cyclophilin B-dependent endoplasmic reticulum-associated degradation.

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Riccardo Bernasconi

2010-09-01

Full Text Available Peptidyl-prolyl cis/trans isomerases (PPIs catalyze cis/trans isomerization of peptide bonds preceding proline residues. The involvement of PPI family members in protein refolding has been established in test tube experiments. Surprisingly, however, no data is available on the involvement of endoplasmic reticulum (ER-resident members of the PPI family in protein folding, quality control or disposal in the living cell. Here we report that the immunosuppressive drug cyclosporine A (CsA selectively inhibits the degradation of a subset of misfolded proteins generated in the ER. We identify cyclophilin B (CyPB as the ER-resident target of CsA that catalytically enhances disposal from the ER of ERAD-L(S substrates containing cis proline residues. Our manuscript presents the first evidence for enzymatic involvement of a PPI in protein quality control in the ER of living cells.

Cyclosporine A-Sensitive, Cyclophilin B-Dependent Endoplasmic Reticulum-Associated Degradation

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Luban, Jeremy; Molinari, Maurizio

2010-01-01

Peptidyl-prolyl cis/trans isomerases (PPIs) catalyze cis/trans isomerization of peptide bonds preceding proline residues. The involvement of PPI family members in protein refolding has been established in test tube experiments. Surprisingly, however, no data is available on the involvement of endoplasmic reticulum (ER)-resident members of the PPI family in protein folding, quality control or disposal in the living cell. Here we report that the immunosuppressive drug cyclosporine A (CsA) selectively inhibits the degradation of a subset of misfolded proteins generated in the ER. We identify cyclophilin B (CyPB) as the ER-resident target of CsA that catalytically enhances disposal from the ER of ERAD-LS substrates containing cis proline residues. Our manuscript presents the first evidence for enzymatic involvement of a PPI in protein quality control in the ER of living cells. PMID:20927389

Structural and kinetic studies of the allosteric transition in Sulfolobus solfataricus uracil phosphoribosyltransferase: Permanent activation by engineering of the C-terminus

DEFF Research Database (Denmark)

Christoffersen, Stig; Kadziola, Anders; Johansson, Eva

2009-01-01

and PPi, in the other sites. Combined with three existing structures of uracil phosphoribosyltransferase in complex with UMP and the allosteric inhibitor cytidine triphosphate (CTP), these structures provide valuable insight into the mechanism of allosteric transition from inhibited to active enzyme...

Co-segregation of hyperactivity, active coping styles, and cognitive dysfunction in mice selectively bred for low levels of anxiety.

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Yen, Yi-Chun; Anderzhanova, Elmira; Bunck, Mirjam; Schuller, Julia; Landgraf, Rainer; Wotjak, Carsten T

2013-01-01

We established mouse models of extremes in trait anxiety, which are based on selective breeding for low vs. normal vs. high open-arm exploration on the elevated plus-maze. Genetically selected low anxiety-related behavior (LAB) coincided with hyperactivity in the home cage. Given the fact that several psychiatric disorders such as schizophrenia, mania, and attention deficit hyperactivity disorder (ADHD) share hyperactivity symptom, we systematically examined LAB mice with respect to unique and overlapping endophenotypes of the three diseases. To this end Venn diagrams were used as an instrument for discrimination of possible models. We arranged the endophenotypes in Venn diagrams and translated them into different behavioral tests. LAB mice showed elevated levels of locomotion in the open field (OF) test with deficits in habituation, compared to mice bred for normal (NAB) and high anxiety-related behavior (HAB). Cross-breeding of hypoactive HAB and hyperactive LAB mice resulted in offspring showing a low level of locomotion comparable to HAB mice, indicating that the HAB alleles are dominant over LAB alleles in determining the level of locomotion. In a holeboard test, LAB mice spent less time in hole exploration, as shown in patients with schizophrenia and ADHD; however, LAB mice displayed no impairments in social interaction and prepulse inhibition (PPI), implying a unlikelihood of LAB as an animal model of schizophrenia. Although LAB mice displayed hyperarousal, active coping styles, and cognitive deficits, symptoms shared by mania and ADHD, they failed to reveal the classic manic endophenotypes, such as increased hedonia and object interaction. The neuroleptic haloperidol reduced locomotor activity in all mouse lines. The mood stabilizer lithium and the psychostimulant amphetamine, in contrast, selectively reduced hyperactivity in LAB mice. Based on the behavioral and pharmacological profiles, LAB mice are suggested as a novel rodent model of ADHD-like symptoms.

Chronic Anabolic Androgenic Steroid Exposure Alters Corticotropin Releasing Factor Expression and Anxiety-Like Behaviors in the Female Mouse

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Costine, Beth A; Oberlander, Joseph G; Davis, Matthew C; Penatti, Carlos A A; Porter, Donna M; Leaton, Robert N; Henderson, Leslie P

2010-01-01

Summary In the past several decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit use of these drugs by elite athletes and a growing number of adolescents to enhance performance and body image. As with adults, AAS use by adolescents is associated with a range of behavioral effects, including increased anxiety and altered responses to stress. It has been suggested that adolescents, especially adolescent females, may be particularly susceptible to the effects of these steroids, but few experiments in animal models have been performed to test this assertion. Here we show that chronic exposure of adolescent female mice to a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and methandrostenolone; 7.5 mg/kg/day for 5 days) significantly enhanced anxiety-like behavior as assessed by the acoustic startle response (ASR), but did not augment the fear-potentiated startle response (FPS) or alter sensorimotor gating as assessed by prepulse inhibition of the acoustic startle response (PPI). AAS treatment also significantly increased the levels of corticotropin releasing factor (CRF) mRNA and somal-associated CRF immunoreactivity in the central amygdala (CeA), as well as neuropil-associated immunoreactivity in the dorsal aspect of the anterolateral division of the bed nucleus of the stria terminalis (dBnST). AAS treatment did not alter CRF receptor 1 or 2 mRNA in either the CeA or the dBnST; CRF immunoreactivity in the ventral BNST, the paraventricular nucleus (PVN) or the median eminence (ME); or peripheral levels of corticosterone. These results suggest that chronic AAS treatment of adolescent female mice may enhance generalized anxiety, but not sensorimotor gating or learned fear, via a mechanism that involves increased CRF-mediated signaling from CeA neurons projecting to the dBnST. PMID:20537804

Association analysis of 94 candidate genes and schizophrenia-related endophenotypes.

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Tiffany A Greenwood

Full Text Available While it is clear that schizophrenia is highly heritable, the genetic basis of this heritability is complex. Human genetic, brain imaging, and model organism studies have met with only modest gains. A complementary research tactic is to evaluate the genetic substrates of quantitative endophenotypes with demonstrated deficits in schizophrenia patients. We used an Illumina custom 1,536-SNP array to interrogate 94 functionally relevant candidate genes for schizophrenia and evaluate association with both the qualitative diagnosis of schizophrenia and quantitative endophenotypes for schizophrenia. Subjects included 219 schizophrenia patients and normal comparison subjects of European ancestry and 76 schizophrenia patients and normal comparison subjects of African ancestry, all ascertained by the UCSD Schizophrenia Research Program. Six neurophysiological and neurocognitive endophenotype test paradigms were assessed: prepulse inhibition (PPI, P50 suppression, the antisaccade oculomotor task, the Letter-Number Span Test, the California Verbal Learning Test-II, and the Wisconsin Card Sorting Test-64 Card Version. These endophenotype test paradigms yielded six primary endophenotypes with prior evidence of heritability and demonstrated schizophrenia-related impairments, as well as eight secondary measures investigated as candidate endophenotypes. Schizophrenia patients showed significant deficits on ten of the endophenotypic measures, replicating prior studies and facilitating genetic analyses of these phenotypes. A total of 38 genes were found to be associated with at least one endophenotypic measure or schizophrenia with an empirical p-value<0.01. Many of these genes have been shown to interact on a molecular level, and eleven genes displayed evidence for pleiotropy, revealing associations with three or more endophenotypic measures. Among these genes were ERBB4 and NRG1, providing further support for a role of these genes in schizophrenia susceptibility

Co-segregation of hyperactivity, active coping styles, and cognitive dysfunction in mice selectively bred for low levels of anxiety

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Yen, Yi-Chun; Anderzhanova, Elmira; Bunck, Mirjam; Schuller, Julia; Landgraf, Rainer; Wotjak, Carsten T.

2013-01-01

We established mouse models of extremes in trait anxiety, which are based on selective breeding for low vs. normal vs. high open-arm exploration on the elevated plus-maze. Genetically selected low anxiety-related behavior (LAB) coincided with hyperactivity in the home cage. Given the fact that several psychiatric disorders such as schizophrenia, mania, and attention deficit hyperactivity disorder (ADHD) share hyperactivity symptom, we systematically examined LAB mice with respect to unique and overlapping endophenotypes of the three diseases. To this end Venn diagrams were used as an instrument for discrimination of possible models. We arranged the endophenotypes in Venn diagrams and translated them into different behavioral tests. LAB mice showed elevated levels of locomotion in the open field (OF) test with deficits in habituation, compared to mice bred for normal (NAB) and high anxiety-related behavior (HAB). Cross-breeding of hypoactive HAB and hyperactive LAB mice resulted in offspring showing a low level of locomotion comparable to HAB mice, indicating that the HAB alleles are dominant over LAB alleles in determining the level of locomotion. In a holeboard test, LAB mice spent less time in hole exploration, as shown in patients with schizophrenia and ADHD; however, LAB mice displayed no impairments in social interaction and prepulse inhibition (PPI), implying a unlikelihood of LAB as an animal model of schizophrenia. Although LAB mice displayed hyperarousal, active coping styles, and cognitive deficits, symptoms shared by mania and ADHD, they failed to reveal the classic manic endophenotypes, such as increased hedonia and object interaction. The neuroleptic haloperidol reduced locomotor activity in all mouse lines. The mood stabilizer lithium and the psychostimulant amphetamine, in contrast, selectively reduced hyperactivity in LAB mice. Based on the behavioral and pharmacological profiles, LAB mice are suggested as a novel rodent model of ADHD-like symptoms

Fat suppression with short inversion time inversion-recovery and chemical-shift selective saturation: a dual STIR-CHESS combination prepulse for turbo spin echo pulse sequences.

Science.gov (United States)

Tanabe, Koji; Nishikawa, Keiichi; Sano, Tsukasa; Sakai, Osamu; Jara, Hernán

2010-05-01

To test a newly developed fat suppression magnetic resonance imaging (MRI) prepulse that synergistically uses the principles of fat suppression via inversion recovery (STIR) and spectral fat saturation (CHESS), relative to pure CHESS and STIR. This new technique is termed dual fat suppression (Dual-FS). To determine if Dual-FS could be chemically specific for fat, the phantom consisted of the fat-mimicking NiCl(2) aqueous solution, porcine fat, porcine muscle, and water was imaged with the three fat-suppression techniques. For Dual-FS and STIR, several inversion times were used. Signal intensities of each image obtained with each technique were compared. To determine if Dual-FS could be robust to magnetic field inhomogeneities, the phantom consisting of different NiCl(2) aqueous solutions, porcine fat, porcine muscle, and water was imaged with Dual-FS and CHESS at the several off-resonance frequencies. To compare fat suppression efficiency in vivo, 10 volunteer subjects were also imaged with the three fat-suppression techniques. Dual-FS could suppress fat sufficiently within the inversion time of 110-140 msec, thus enabling differentiation between fat and fat-mimicking aqueous structures. Dual-FS was as robust to magnetic field inhomogeneities as STIR and less vulnerable than CHESS. The same results for fat suppression were obtained in volunteers. The Dual-FS-STIR-CHESS is an alternative and promising fat suppression technique for turbo spin echo MRI. Copyright 2010 Wiley-Liss, Inc.

Corrosion Protection of Steels by Conducting Polymer Coating

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Toshiaki Ohtsuka

2012-01-01

Full Text Available The corrosion protection of steels by conducting polymer coating is reviewed. The conducting polymer such as polyaniline, polypyrrole, and polythiophen works as a strong oxidant to the steel, inducing the potential shift to the noble direction. The strongly oxidative conducting polymer facilitates the steel to be passivated. A bilayered PPy film was designed for the effective corrosion protection. It consisted of the inner layer in which phosphomolybdate ion, PMo12O3−40 (PMo, was doped and the outer layer in which dodecylsulfate ion (DoS was doped. The inner layer stabilized the passive oxide and the outer possessed anionic perm-selectivity to inhibit the aggressive anions such as chloride from penetrating through the PPy film to the substrate steel. By the bilayered PPy film, the steel was kept passive for about 200 h in 3.5% sodium chloride solution without formation of corrosion products.

Neonatal exposure to phenobarbital potentiates schizophrenia-like behavioral outcomes in the rat.

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Bhardwaj, S K; Forcelli, P A; Palchik, G; Gale, K; Srivastava, L K; Kondratyev, A

2012-06-01

Previous work has indicated an association between seizures early in life and increased risk of psychiatric disorders, including schizophrenia. However, because early-life seizures are commonly treated with antiepileptic drugs (AEDs) such as phenobarbital, the possibility that drug treatment may affect later-life psychiatric outcomes needs to be evaluated. We therefore tested the hypothesis that phenobarbital exposure in the neonatal rat increases the risk of schizophrenia-like behavioral abnormalities in adulthood. Thus, in this study, we examined the effects of a single acute neonatal exposure to phenobarbital on adult behavioral outcomes in the rat neonatal ventral hippocampal (nVH) lesion model of schizophrenia. We compared these outcomes to those in rats a) without nVH lesions and b) with nVH lesions, without phenobarbital. The tasks used for behavioral evaluation were: amphetamine-induced locomotion, prepulse inhibition, elevated plus-maze, and novel object recognition task. We found that neonatal phenobarbital treatment (in the absence of nVH lesions) was sufficient to disrupt sensorimotor gating (as tested by prepulse inhibition) in adulthood to an extent equivalent to nVH lesions. Additionally, neonatal phenobarbital exposure enhanced the locomotor response to amphetamine in adult animals with and without nVH lesions. Our findings suggest that neonatal exposure to phenobarbital can predispose to schizophrenia-like behavioral abnormalities. Our findings underscore the importance of examining AED exposure early in life as a potential risk factor for later-life neuropsychiatric abnormalities in clinical populations. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effects of the selective 5-HT7 receptor antagonist SB-269970 and amisulpride on ketamine-induced schizophrenia-like deficits in rats.

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Agnieszka Nikiforuk

Full Text Available A wide body of evidence suggests that 5-HT7 receptors are implicated in a variety of central nervous system functions, including control of learning and memory processes. According to recent preclinical data, the selective blockade of these receptors may be a potential target for cognitive improvement in schizophrenia. The first aim of the present study was to evaluate the effects of the selective 5-HT7 receptor antagonist, SB-269970, and the antipsychotic drug with a high affinity for 5-HT7 receptors, amisulpride, on ketamine-induced deficits in attentional set-shifting and novel object recognition tasks in rats. Because the role of 5-HT7 receptor blockade in ameliorating positive and negative symptoms of schizophrenia remains equivocal, the second aim of these experiments was to examine the effectiveness of SB-269970 and amisulpride in reversing ketamine-induced deficits in prepulse inhibition of the startle reflex and in social interaction test in rats. The study revealed that acute administration of SB-269970 (1 mg/kg or amisulpride (3 mg/kg ameliorated ketamine-induced cognitive inflexibility and novel object recognition deficit in rats. Both compounds were also effective in attenuating ketamine-evoked disruption of social interactions. In contrast, neither SB-269970 nor amisulpride affected ketamine-disrupted prepulse inhibition or 50 kHz USVs accompanying social behaviour. In conclusion, antagonism of 5-HT7 receptors may represent a useful pharmacological approach in the treatment of cognitive deficits and some negative symptoms of schizophrenia.

Inhibition of Rac1 ameliorates neuronal oxidative stress damage via reducing Bcl-2/Rac1 complex formation in mitochondria through PI3K/Akt/mTOR pathway.

Science.gov (United States)

Pan, Yundan; Wang, Na; Xia, Pingping; Wang, E; Guo, Qulian; Ye, Zhi

2018-02-01

Although the neuroprotective effects of Rac1 inhibition have been reported in various cerebral ischemic models, the molecular mechanisms of action have not yet been fully elucidated. In this study, we investigated whether the inhibition of Rac1 provided neuroprotection in a diabetic rat model of focal cerebral ischemia and hyperglycemia-exposed PC-12 cells. Intracerebroventricular administration of lentivirus expressing the Rac1 small hairpin RNA (shRNA) and specific Rac1 inhibitor NSC23766 not only decreased the infarct volumes and improved neurologic deficits with a correlated significant activation of mitochondrial DNA specific proteins, such as OGG1 and POLG, but also elevated Bcl-2 S70 phosphorylation in mitochondria. Furthermore, the levels of p-PI3K, p-Akt and p-mTOR increased, while 8-OHdG, ROS production and Bcl-2/Rac1 complex formation in mitochondria reduced in both Rac1-shRNA- and NSC23766-treated rats. Moreover, to confirm our in vivo observations, inhibition of Rac1 activity by NSC23766 suppressed the interactions between Bcl-2 and Rac1 in the mitochondria of PC-12 cells cultured in high glucose conditions and protected PC-12 cells from high glucose-induced neurotoxicity. More importantly, these beneficial effects of Rac1 inhibition were abolished by PI3K inhibitor LY294002. In contrast to NSC23766 treatment, LY294002 had little effect on the decrement of p-PTEN level. Taken together, these findings revealed novel neuroprotective roles of Rac1 inhibition against cerebral ischemic reperfusion injury in vivo and high glucose-induced neurotoxicity in PC-12 cells in vitro, by reducing Bcl-2/Rac1 complex formation in mitochondria through the activation of PI3K/Akt/mTOR survival pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Survey of findings in patients having persistent heartburn on proton pump inhibitor therapy.

Science.gov (United States)

Mandaliya, R; DiMarino, A J; Cohen, S

2016-01-01

In patients with refractory heartburn while on proton pump inhibitor (PPI) therapy, changing drugs or increasing treatment to a twice a day (b.i.d.) dose has become a common practice. This study aims to study patients with persistent heartburn while on PPI therapy and to determine if persistent symptom indicates the need for more aggressive or different therapy. A retrospective review of impedance-pH tracings on PPI therapy (q.d. or b.i.d.) for patients with persistent heartburn was performed. DeMeester score, impedance, and symptom sensitive index (SSI) were used as indices. Statistical analyses were performed using chi-squared test with Yates correction and paired t-test. One hundred consecutive patients, (female 50%, male 50%, mean age 54 [range 16-83] years) were studied on q.d. (n = 45) or b.i.d. PPI (n = 55). Only 20% of the patients had abnormal DeMeester score; 41% had an abnormal impedance score and 56% had abnormal SSI; 29% had all indices normal. There was no difference between patients taking q.d. versus b.i.d. PPI for abnormal DeMeester score (22 vs. 18%), impedance (38 vs. 44%) and SSI (53 vs. 58%); P = 0.80, 0.69, and 0.77, respectively. In 56 patients with positive SSI, symptoms were due to acid reflux in 8 (14%) patients, nonacid reflux in 31 (55%) patients, and combined acid and nonacid reflux in 17 (30%) patients. Patients with persistent heartburn on PPI therapy show a variety of disorders: (i) acid reflux (20%); (ii) nonacid reflux (26%); (iii) positive SSI (56%); (iv) all normal indices (29%). These studies indicate that persistent heartburn on PPI therapy is a complex problem that may not respond to simply increasing acid inhibition. © 2014 International Society for Diseases of the Esophagus.

Proton pump inhibitors inhibit pancreatic secretion

DEFF Research Database (Denmark)

Wang, Jing; Barbuskaite, Dagne; Tozzi, Marco

2015-01-01

+/K+-ATPases are expressed and functional in human pancreatic ducts and whether proton pump inhibitors (PPIs) have effect on those. Here we show that the gastric HKα1 and HKβ subunits (ATP4A; ATP4B) and non-gastric HKα2 subunits (ATP12A) of H+/K+-ATPases are expressed in human pancreatic cells. Pumps have similar...... of major ions in secretion follow similar excretory curves in control and PPI treated animals. In addition to HCO3-, pancreas also secretes K+. In conclusion, this study calls for a revision of the basic model for HCO3- secretion. We propose that proton transport is driving secretion, and that in addition...

Dopamine, nitric oxide and their interactions in models for the study of schizophrenia / Dopamina, óxido nítrico e suas interações em modelos para o estudo da esquizofrenia

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Cristiane Salum

2008-01-01

Full Text Available Experimental models based on the increase of dopaminergic neurotransmission mimic behavioral and neurochemical schizophrenia-like aspects. Psychostimulants, as amphetamine, are used with this purpose because they increase extracellular dopamine levels in mesocorticolimbic and mesostriatal pathways. The limitations of direct manipulation uniquely based on the dopamine system in animal models have encouraged the use of new approaches. Nitric oxide (NO, an atypical neurotransmitter which inhibits dopamine reuptake and stimulates its release, seems to modulate dopamine-controlled behaviors. The prepulse inhibition test reveals deficits on the sensorimotor filter found in schizophrenics or after psichotomimetic treatments. This review presents evidences for the interaction between NO and DA systems on schizophrenia models as a new tool for the investigation of this pathology.

Identification of ligand-selective peptidic ActRIIB-antagonists using phage display technology

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Kotaro Sakamoto

2017-09-01

Full Text Available ActRIIB (activin receptor type-2B is an activin receptor subtype constitutively expressed in the whole body, playing a role in cellular proliferation, differentiation, and metabolism. For its various physiological activities, ActRIIB interacts with activin and multiple other ligands including myostatin (MSTN, growth differentiation factor 11 (GDF11, and bone morphogenetic protein 9 (BMP9. Notably, the protein-protein interaction (PPI between ActRIIB and MSTN negatively controls muscular development. Therefore, this PPI has been targeted for effective treatment of muscle degenerative diseases such as muscular dystrophy and sarcopenia. Here, we report the identification of ligand-selective peptidic ActRIIB-antagonists by phage display technology. Our peptides bound to the extracellular domain of ActRIIB, inhibited PPIs between ActRIIB expressed on the cell surface and its ligands, and subsequently suppressed activation of Smad that serves as the downstream signal of the ActRIIB pathway. Interestingly, these peptidic antagonists displayed different ligand selectivities; the AR2mini peptide inhibited multiple ligands (activin A, MSTN, GDF11, and BMP9, AR9 inhibited MSTN and GDF11, while AR8 selectively inhibited MSTN. This is the first report of artificial peptidic ActRIIB-antagonists possessing ligand-selectivity.

Lansoprazole and carbonic anhydrase IX inhibitors sinergize against human melanoma cells.

Science.gov (United States)

Federici, Cristina; Lugini, Luana; Marino, Maria Lucia; Carta, Fabrizio; Iessi, Elisabetta; Azzarito, Tommaso; Supuran, Claudiu T; Fais, Stefano

2016-01-01

Proton Pump Inhibitors (PPIs) reduce tumor acidity and therefore resistance of tumors to drugs. Carbonic Anhydrase IX (CA IX) inhibitors have proven to be effective against tumors, while tumor acidity might impair their full effectiveness. To analyze the effect of PPI/CA IX inhibitors combined treatment against human melanoma cells. The combination of Lansoprazole (LAN) and CA IX inhibitors (FC9-399A and S4) has been investigated in terms of cell proliferation inhibition and cell death in human melanoma cells. The combination of these inhibitors was more effective than the single treatments in both inhibiting cell proliferation and in inducing cell death in human melanoma cells. These results represent the first successful attempt in combining two different proton exchanger inhibitors. This is the first evidence on the effectiveness of a new approach against tumors based on the combination of PPI and CA IX inhibitors, thus providing an alternative strategy against tumors.

Clopidogrel and proton pump inhibitors--where do we stand in 2012?

LENUS (Irish Health Repository)

Drepper, Michael D

2012-05-14

Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events. Concomitant treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical guidelines. Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19 (CYP2C19) and proton pump inhibitors (PPIs) are extensively metabolized by the CYP2C19 isoenzyme as well. Several pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole, but not for pantoprazole. Initial clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events, when under clopidogrel and PPI treatment at the same time. These observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI (especially omeprazole) in the same year. In contrast, more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on clopidogrel. Three meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality, with high and moderate quality studies not reporting any association, rising concern about unmeasured confounders biasing the low quality studies. Thus, no definite evidence exists for an effect on mortality. Because PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding, combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended.

Dynamic programming re-ranking for PPI interactor and pair extraction in full-text articles

Science.gov (United States)

2011-01-01

Background Experimentally verified protein-protein interactions (PPIs) cannot be easily retrieved by researchers unless they are stored in PPI databases. The curation of such databases can be facilitated by employing text-mining systems to identify genes which play the interactor role in PPIs and to map these genes to unique database identifiers (interactor normalization task or INT) and then to return a list of interaction pairs for each article (interaction pair task or IPT). These two tasks are evaluated in terms of the area under curve of the interpolated precision/recall (AUC iP/R) score because the order of identifiers in the output list is important for ease of curation. Results Our INT system developed for the BioCreAtIvE II.5 INT challenge achieved a promising AUC iP/R of 43.5% by using a support vector machine (SVM)-based ranking procedure. Using our new re-ranking algorithm, we have been able to improve system performance (AUC iP/R) by 1.84%. Our experimental results also show that with the re-ranked INT results, our unsupervised IPT system can achieve a competitive AUC iP/R of 23.86%, which outperforms the best BC II.5 INT system by 1.64%. Compared to using only SVM ranked INT results, using re-ranked INT results boosts AUC iP/R by 7.84%. Statistical significance t-test results show that our INT/IPT system with re-ranking outperforms that without re-ranking by a statistically significant difference. Conclusions In this paper, we present a new re-ranking algorithm that considers co-occurrence among identifiers in an article to improve INT and IPT ranking results. Combining the re-ranked INT results with an unsupervised approach to find associations among interactors, the proposed method can boost the IPT performance. We also implement score computation using dynamic programming, which is faster and more efficient than traditional approaches. PMID:21342534

Exosome release and low pH belong to a framework of resistance of human melanoma cells to cisplatin.

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Cristina Federici

Full Text Available Intrinsic resistance to cytotoxic drugs has been a main issue in cancer therapy for decades. Microenvironmental acidity is a simple while highly efficient mechanism of chemoresistance, exploited through impairment of drug delivery. The latter is achieved by extracellular protonation and/or sequestration into acidic vesicles. This study investigates the importance of extracellular acidosis and nanovesicle (exosome release in the resistance of human tumour cell to cisplatin (CisPt; in parallel to proton pump inhibitors (PPI ability of interfering with these tumour cell features. The results showed that CisPt uptake by human tumour cells was markedly impaired by low pH conditions. Moreover, exosomes purified from supernatants of these cell cultures contained various amounts of CisPt, which correlated to the pH conditions of the culture medium. HPLC-Q-ICP-MS analysis revealed that exosome purified from tumour cell culture supernatants contained CisPt in its native form. PPI pre-treatment increased cellular uptake of CisPt, as compared to untreated cells, in an acidic-depend manner. Furthermore, it induced a clear inhibition of exosome release by tumour cells. Human tumours obtained from xenografts pretreated with PPI contained more CisPt as compared to tumours from xenografts treated with CisPt alone. Further analysis showed that in vivo PPI treatment induced a clear reduction in the plasmatic levels of tumour-derived exosomes which also contained lower level of CisPt. Altogether, these findings point to the identification of a double mechanism that human malignant melanoma use in resisting to a dreadful cellular poison such as cisplatin. This framework of resistance includes both low pH-dependent extracellular sequestration and an exosome-mediated elimination. Both mechanisms are markedly impaired by proton pump inhibition, leading to an increased CisPt-dependent cytotoxicity.

Exosome release and low pH belong to a framework of resistance of human melanoma cells to cisplatin.

Science.gov (United States)

Federici, Cristina; Petrucci, Francesco; Caimi, Stefano; Cesolini, Albino; Logozzi, Mariantonia; Borghi, Martina; D'Ilio, Sonia; Lugini, Luana; Violante, Nicola; Azzarito, Tommaso; Majorani, Costanza; Brambilla, Daria; Fais, Stefano

2014-01-01

Intrinsic resistance to cytotoxic drugs has been a main issue in cancer therapy for decades. Microenvironmental acidity is a simple while highly efficient mechanism of chemoresistance, exploited through impairment of drug delivery. The latter is achieved by extracellular protonation and/or sequestration into acidic vesicles. This study investigates the importance of extracellular acidosis and nanovesicle (exosome) release in the resistance of human tumour cell to cisplatin (CisPt); in parallel to proton pump inhibitors (PPI) ability of interfering with these tumour cell features. The results showed that CisPt uptake by human tumour cells was markedly impaired by low pH conditions. Moreover, exosomes purified from supernatants of these cell cultures contained various amounts of CisPt, which correlated to the pH conditions of the culture medium. HPLC-Q-ICP-MS analysis revealed that exosome purified from tumour cell culture supernatants contained CisPt in its native form. PPI pre-treatment increased cellular uptake of CisPt, as compared to untreated cells, in an acidic-depend manner. Furthermore, it induced a clear inhibition of exosome release by tumour cells. Human tumours obtained from xenografts pretreated with PPI contained more CisPt as compared to tumours from xenografts treated with CisPt alone. Further analysis showed that in vivo PPI treatment induced a clear reduction in the plasmatic levels of tumour-derived exosomes which also contained lower level of CisPt. Altogether, these findings point to the identification of a double mechanism that human malignant melanoma use in resisting to a dreadful cellular poison such as cisplatin. This framework of resistance includes both low pH-dependent extracellular sequestration and an exosome-mediated elimination. Both mechanisms are markedly impaired by proton pump inhibition, leading to an increased CisPt-dependent cytotoxicity.

Annotating activation/inhibition relationships to protein-protein interactions using gene ontology relations.

Science.gov (United States)

Yim, Soorin; Yu, Hasun; Jang, Dongjin; Lee, Doheon

2018-04-11

Signaling pathways can be reconstructed by identifying 'effect types' (i.e. activation/inhibition) of protein-protein interactions (PPIs). Effect types are composed of 'directions' (i.e. upstream/downstream) and 'signs' (i.e. positive/negative), thereby requiring directions as well as signs of PPIs to predict signaling events from PPI networks. Here, we propose a computational method for systemically annotating effect types to PPIs using relations between functional information of proteins. We used regulates, positively regulates, and negatively regulates relations in Gene Ontology (GO) to predict directions and signs of PPIs. These relations indicate both directions and signs between GO terms so that we can project directions and signs between relevant GO terms to PPIs. Independent test results showed that our method is effective for predicting both directions and signs of PPIs. Moreover, our method outperformed a previous GO-based method that did not consider the relations between GO terms. We annotated effect types to human PPIs and validated several highly confident effect types against literature. The annotated human PPIs are available in Additional file 2 to aid signaling pathway reconstruction and network biology research. We annotated effect types to PPIs by using regulates, positively regulates, and negatively regulates relations in GO. We demonstrated that those relations are effective for predicting not only signs, but also directions of PPIs. The usefulness of those relations suggests their potential applications to other types of interactions such as protein-DNA interactions.

Characterizing Protein Interactions Employing a Genome-Wide siRNA Cellular Phenotyping Screen

Science.gov (United States)

Suratanee, Apichat; Schaefer, Martin H.; Betts, Matthew J.; Soons, Zita; Mannsperger, Heiko; Harder, Nathalie; Oswald, Marcus; Gipp, Markus; Ramminger, Ellen; Marcus, Guillermo; Männer, Reinhard; Rohr, Karl; Wanker, Erich; Russell, Robert B.; Andrade-Navarro, Miguel A.; Eils, Roland; König, Rainer

2014-01-01

Characterizing the activating and inhibiting effect of protein-protein interactions (PPI) is fundamental to gain insight into the complex signaling system of a human cell. A plethora of methods has been suggested to infer PPI from data on a large scale, but none of them is able to characterize the effect of this interaction. Here, we present a novel computational development that employs mitotic phenotypes of a genome-wide RNAi knockdown screen and enables identifying the activating and inhibiting effects of PPIs. Exemplarily, we applied our technique to a knockdown screen of HeLa cells cultivated at standard conditions. Using a machine learning approach, we obtained high accuracy (82% AUC of the receiver operating characteristics) by cross-validation using 6,870 known activating and inhibiting PPIs as gold standard. We predicted de novo unknown activating and inhibiting effects for 1,954 PPIs in HeLa cells covering the ten major signaling pathways of the Kyoto Encyclopedia of Genes and Genomes, and made these predictions publicly available in a database. We finally demonstrate that the predicted effects can be used to cluster knockdown genes of similar biological processes in coherent subgroups. The characterization of the activating or inhibiting effect of individual PPIs opens up new perspectives for the interpretation of large datasets of PPIs and thus considerably increases the value of PPIs as an integrated resource for studying the detailed function of signaling pathways of the cellular system of interest. PMID:25255318

Effects of prenatal exposure to surface-coated nanosized titanium dioxide (UV-Titan). A study in mice

DEFF Research Database (Denmark)

Hougaard, Karin S.; Jackson, Petra; Jensen, Keld A.

2010-01-01

to a nanoparticulate UV-filter (UV-titan L181). Methods: Time-mated mice (C57BL/6BomTac) were exposed by inhalation 1h/day to 42 mg/m(3) aerosolized powder (1.7.10(6) n/cm(3); peak-size: 97 nm) on gestation days 8-18. Endpoints included: maternal lung inflammation; gestational and litter parameters; offspring...... the central zone of the open field and exposed female offspring displayed enhanced prepulse inhibition. Cognitive function was unaffected (Morris water maze test). Conclusion: Inhalation exposure to nano-sized UV Titan dusts induced long term lung inflammation in time-mated adult female mice. Gestationally...

Antitumor effect of triptolide in T-cell lymphoblastic lymphoma by inhibiting cell viability, invasion, and epithelial–mesenchymal transition via regulating the PI3K/AKT/mTOR pathway

Directory of Open Access Journals (Sweden)

Huang Y

2018-02-01

Full Text Available Yan Huang, Sun Wu, Yuan Zhang, Lihua Wang, Yan Guo Department of Hematology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, People’s Republic of China Introduction: T-cell lymphoblastic lymphoma (T-LBL is a widely disseminated disease worldwide. Triptolide (TPL is purified from Chinese herb and displays anti-inflammatory, anti-fertility, anti-tumor and immunosuppressive effects. Materials and methods: Here, in vitro and in vivo experiments were conducted to investigate the anti-tumor effect of TPL treatment in T-LBL and the potential mechanism in T-LBL progression. Results: TPL inhibited cell proliferation of T-LBL cells (Jurkat cells and Molt-3 cells in a dose-dependent manner. Flow cytometry analysis showed that cell apoptosis rate was increased by TPL treatment. TPL also up-regulated the expression of Caspase-3, Bax and down-regulated the expression of Bcl-2, indicating that TPL promoted apoptosis in Jurkat cells. Moreover, TPL inhibited invasion ability of Jurkat cells and down-regulated the expression of MMP-3 and MMP-9 in a dose-dependent manner. The expression of Snail, Slug, Twist and Integrin αVβ6 was decreased and the expression of E-cadherin was increased by TPL treatment, indicating that TPL inhibited EMT of Jurkat cells. Apart from that, TPL treatment attenuated the phoslevels of PI3K, Akt and mTOR and suppressed AKT activation compared with control group, suggesting that TPL inhibited PI3K/Akt/mTOR signal pathway in T-LBL. In vivo experiments showed that TPL inhibited tumor growth of T-LBL and promoted apoptosis of tumor cells. The expression of PCNA, Bcl-2, Snail, p-PI3K, p-Akt and mTOR was suppressed by TPL in a dose-dependent manner, suggesting that TPL suppressed tumor growth and promoted apoptosis of tumor cells by inhibiting PI3K/Akt/mTOR signal pathway in T-LBL. Conclusion: In conclusion, TPL exerted anti-tumor effect in T-LBL by inhibiting cell viability, invasion and EMT via regulating the PI3K

The Gαh-PLCδ1 signaling axis drives metastatic progression in triple-negative breast cancer.

Science.gov (United States)

Huang, Shang-Pen; Liu, Pei-Yao; Kuo, Chih-Jung; Chen, Chi-Long; Lee, Wei-Jiunn; Tsai, Yu-Hui; Lin, Yuan-Feng

2017-06-02

Distant metastasis of triple-negative breast cancer (TNBC) to other organs, e.g., the lungs, has been correlated with poor survival rates among breast cancer patients. Therefore, the identification of useful therapeutic targets to prevent metastasis or even inhibit tumor growth of TNBC is urgently needed. Gαh is a novel GTP-binding protein and known as an inactive form of calcium-dependent tissue transglutaminase. However, the functional consequences of transamidating and G-protein activities of tissue transglutaminase in promoting cancer metastasis are still controversial. Kaplan-Meier analyses were performed to estimate the prognostic values of Gαh and PLCδ1 by utilizing public databases and performing immunohistochemical staining experiments. Cell-based invasion assays and in vivo lung colony-forming and orthotropic lung metastasis models were established to evaluate the effectiveness of interrupting the protein-protein interaction (PPI) between Gαh and PLCδ1 in inhibiting the invasive ability and metastatic potential of TNBC cells. Here, we showed that the increased level of cytosolic, not extracellular, Gαh is a poor prognostic marker in breast cancer patients and correlates with the metastatic evolution of TNBC cells. Moreover, clinicopathological analyses revealed that the combined signature of high Gαh/PLCδ1 levels indicates worse prognosis in patients with breast cancer and correlates with lymph node metastasis of ER-negative breast cancer. Blocking the PPI of the Gαh/PLCδ1 complex by synthetically myristoylated PLCδ1 peptide corresponding to the Gαh-binding interface appeared to significantly suppress cellular invasiveness in vitro and inhibit lung metastatic colonies of TNBC cells in vivo. This study establishes Gαh/PLCδ1 as a poor prognostic factor for patients with estrogen receptor-negative breast cancers, including TNBCs, and provides therapeutic value by targeting the PPI of the Gαh/PLCδ1 complex to combat the metastatic progression

Anxiety and retrieval inhibition: support for an enhanced inhibition account.

Science.gov (United States)

Nuñez, Mia; Gregory, Josh; Zinbarg, Richard E

2017-02-01

Retrieval inhibition of negative associations is important for exposure therapy for anxiety, but the relationship between memory inhibition and anxiety is not well understood-anxiety could either be associated with enhanced or deficient inhibition. The present study tested these two competing hypotheses by measuring retrieval inhibition of negative stimuli by related neutral stimuli. Non-clinically anxious undergraduates completed measures of trait and state anxiety and completed a retrieval induced forgetting task. Adaptive forgetting varied with state anxiety. Low levels of state anxiety were associated with no evidence for retrieval inhibition for either threatening or non-threatening categories. Participants in the middle tertile of state anxiety scores exhibited retrieval inhibition for non-threatening categories but not for threatening categories. Participants in the highest tertile of state anxiety, however, exhibited retrieval inhibition for both threatening and non-threatening categories with the magnitude of retrieval inhibition being greater for threatening than non-threatening categories. The data are in line with the avoidance aspect of the vigilance-avoidance theory of anxiety and inhibition. Implications for cognitive behavioural therapy practices are discussed.

Optically controlled seeding of Raman forward scattering and injection of electrons in a self-modulated laser-wakefield accelerator

International Nuclear Information System (INIS)

Chen, W.-T.; Chien, T.-Y.; Lee, C.-H.; Lin, J.-Y.; Wang, J.; Chen, S.-Y.

2004-01-01

Optical seeding of plasma waves and the injection of electrons are key issues in self-modulated laser-wakefield accelerators. By implementing a copropagating laser prepulse with proper timing, we are able to control the growth of Raman forward scattering and the production of accelerated electrons. The dependence of the Raman intensity on prepulse timing indicates that the seeding of Raman forward scattering is dominated by the ionization-induced wakefield, and the dependence of the divergence and number of accelerated electrons further reveals that the stimulated Raman backward scattering of the prepulse plays the essential role of injecting hot electrons into the fast plasma wave driven by the main pulse

DNA-inorganic hybrid nanovaccine for cancer immunotherapy

Science.gov (United States)

Zhu, Guizhi; Liu, Yijing; Yang, Xiangyu; Kim, Young-Hwa; Zhang, Huimin; Jia, Rui; Liao, Hsien-Shun; Jin, Albert; Lin, Jing; Aronova, Maria; Leapman, Richard; Nie, Zhihong; Niu, Gang; Chen, Xiaoyuan

2016-03-01

Cancer evolves to evade or compromise the surveillance of the immune system, and cancer immunotherapy aims to harness the immune system in order to inhibit cancer development. Unmethylated CpG dinucleotide-containing oligonucleotides (CpG), a class of potent adjuvants that activate the toll-like receptor 9 (TLR9) located in the endolysosome of many antigen-presenting cells (APCs), are promising for cancer immunotherapy. However, clinical application of synthetic CpG confronts many challenges such as suboptimal delivery into APCs, unfavorable pharmacokinetics caused by limited biostability and short in vivo half-life, and side effects associated with leaking of CpG into the systemic circulation. Here we present DNA-inorganic hybrid nanovaccines (hNVs) for efficient uptake into APCs, prolonged tumor retention, and potent immunostimulation and cancer immunotherapy. hNVs were self-assembled from concatemer CpG analogs and magnesium pyrophosphate (Mg2PPi). Mg2PPi renders hNVs resistant to nuclease degradation and thermal denaturation, both of which are demanding characteristics for effective vaccination and the storage and transportation of vaccines. Fluorophore-labeled hNVs were tracked to be efficiently internalized into the endolysosomes of APCs, where Mg2PPi was dissolved in an acidic environment and thus CpG analogs were exposed to hNVs. Internalized hNVs in APCs led to (1) elevated secretion of proinflammatory factors, and (2) elevated expression of co-stimulatory factors. Compared with molecular CpG, hNVs dramatically prolonged the tissue retention of CpG analogs and reduced splenomegaly, a common side effect of CpG. In a melanoma mouse model, two injections of hNVs significantly inhibited the tumor growth and outperformed the molecular CpG. These results suggest hNVs are promising for cancer immunotherapy.Cancer evolves to evade or compromise the surveillance of the immune system, and cancer immunotherapy aims to harness the immune system in order to inhibit

The gap-startle paradigm to assess auditory temporal processing: Bridging animal and human research.

Science.gov (United States)

Fournier, Philippe; Hébert, Sylvie

2016-05-01

The gap-prepulse inhibition of the acoustic startle (GPIAS) paradigm is the primary test used in animal research to identify gap detection thresholds and impairment. When a silent gap is presented shortly before a loud startling stimulus, the startle reflex is inhibited and the extent of inhibition is assumed to reflect detection. Here, we applied the same paradigm in humans. One hundred and fifty-seven normal-hearing participants were tested using one of five gap durations (5, 25, 50, 100, 200 ms) in one of the following two paradigms-gap-embedded in or gap-following-the continuous background noise. The duration-inhibition relationship was observable for both conditions but followed different patterns. In the gap-embedded paradigm, GPIAS increased significantly with gap duration up to 50 ms and then more slowly up to 200 ms (trend only). In contrast, in the gap-following paradigm, significant inhibition-different from 0--was observable only at gap durations from 50 to 200 ms. The finding that different patterns are found depending on gap position within the background noise is compatible with distinct mechanisms underlying each of the two paradigms. © 2016 Society for Psychophysiological Research.

MCH and apomorphine in combination enhance action potential firing of nucleus accumbens shell neurons in vitro

Directory of Open Access Journals (Sweden)

F Woodward Hopf

2013-04-01

Full Text Available The MCH and dopamine receptor systems have been shown to modulate a number of behaviors related to reward processing, addiction, and neuropsychiatric conditions such as schizophrenia and depression. In addition, MCH and dopamine receptors can interact in a positive manner, for example in the expression of cocaine self-administration. A recent report (Chung et al., 2011a showed that the DA1/DA2 dopamine receptor activator apomorphine suppresses pre-pulse inhibition, a preclinical model for some aspects of schizophrenia. Importantly, MCH can enhance the effects of lower doses of apomorphine, suggesting that co-modulation of dopamine and MCH receptors might alleviate some symptoms of schizophrenia with a lower dose of dopamine receptor modulator and thus fewer potential side effects. Here, we investigated whether MCH and apomorphine could enhance action potential firing in vitro in the nucleus accumbens shell (NAshell, a region which has previously been shown to mediate some behavioral effects of MCH. Using whole-cell patch-clamp electrophysiology, we found that MCH, which has no effect on firing on its own, was able to increase NAshell firing when combined with a subthreshold dose of apomorphine. Further, this MCH/apomorphine increase in firing was prevented by an antagonist of either a DA1 or a DA2 receptor, suggesting that apomorphine acts through both receptor types to enhance NAshell firing. The MCH/apomorphine-mediated firing increase was also prevented by an MCH receptor antagonist or a PKA inhibitor. Taken together, our results suggest that MCH can interact with lower doses of apomorphine to enhance NAshell firing, and thus that MCH and apomorphine might interact in vivo within the NAshell to suppress pre-pulse inhibition.

Rasd2 Modulates Prefronto-Striatal Phenotypes in Humans and 'Schizophrenia-Like Behaviors' in Mice.

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Vitucci, Daniela; Di Giorgio, Annabella; Napolitano, Francesco; Pelosi, Barbara; Blasi, Giuseppe; Errico, Francesco; Attrotto, Maria Teresa; Gelao, Barbara; Fazio, Leonardo; Taurisano, Paolo; Di Maio, Anna; Marsili, Valentina; Pasqualetti, Massimo; Bertolino, Alessandro; Usiello, Alessandro

2016-02-01

Rasd2 is a thyroid hormone target gene, which encodes for a GTP-binding protein enriched in the striatum where, among other functions, it modulates dopaminergic neurotransmission. Here we report that human RASD2 mRNA is abundant in putamen, but it also occurs in the cerebral cortex, with a distinctive expression pattern that differs from that present in rodents. Consistent with its localization, we found that a genetic variation in RASD2 (rs6518956) affects postmortem prefrontal mRNA expression in healthy humans and is associated with phenotypes of relevance to schizophrenia, including prefrontal and striatal grey matter volume and physiology during working memory, as measured with magnetic resonance imaging. Interestingly, quantitative real-time PCR analysis indicated that RASD2 mRNA is slightly reduced in postmortem prefrontal cortex of patients with schizophrenia. In the attempt to uncover the neurobiological substrates associated with Rasd2 activity, we used knockout mice to analyze the in vivo influence of this G-protein on the prepulse inhibition of the startle response and psychotomimetic drug-related behavioral response. Data showed that Rasd2 mutants display deficits in basal prepulse inhibition that, in turn, exacerbate gating disruption under psychotomimetic drug challenge. Furthermore, we documented that lack of Rasd2 strikingly enhances the behavioral sensitivity to motor stimulation elicited by amphetamine and phencyclidine. Based on animal model data, along with the finding that RASD2 influences prefronto-striatal phenotypes in healthy humans, we suggest that genetic mutation or reduced levels of this G-protein might have a role in cerebral circuitry dysfunction underpinning exaggerated psychotomimetic drugs responses and development of specific biological phenotypes linked to schizophrenia.

Rasd2 Modulates Prefronto-Striatal Phenotypes in Humans and ‘Schizophrenia-Like Behaviors' in Mice

Science.gov (United States)

Vitucci, Daniela; Di Giorgio, Annabella; Napolitano, Francesco; Pelosi, Barbara; Blasi, Giuseppe; Errico, Francesco; Attrotto, Maria Teresa; Gelao, Barbara; Fazio, Leonardo; Taurisano, Paolo; Di Maio, Anna; Marsili, Valentina; Pasqualetti, Massimo; Bertolino, Alessandro; Usiello, Alessandro

2016-01-01

Rasd2 is a thyroid hormone target gene, which encodes for a GTP-binding protein enriched in the striatum where, among other functions, it modulates dopaminergic neurotransmission. Here we report that human RASD2 mRNA is abundant in putamen, but it also occurs in the cerebral cortex, with a distinctive expression pattern that differs from that present in rodents. Consistent with its localization, we found that a genetic variation in RASD2 (rs6518956) affects postmortem prefrontal mRNA expression in healthy humans and is associated with phenotypes of relevance to schizophrenia, including prefrontal and striatal grey matter volume and physiology during working memory, as measured with magnetic resonance imaging. Interestingly, quantitative real-time PCR analysis indicated that RASD2 mRNA is slightly reduced in postmortem prefrontal cortex of patients with schizophrenia. In the attempt to uncover the neurobiological substrates associated with Rasd2 activity, we used knockout mice to analyze the in vivo influence of this G-protein on the prepulse inhibition of the startle response and psychotomimetic drug-related behavioral response. Data showed that Rasd2 mutants display deficits in basal prepulse inhibition that, in turn, exacerbate gating disruption under psychotomimetic drug challenge. Furthermore, we documented that lack of Rasd2 strikingly enhances the behavioral sensitivity to motor stimulation elicited by amphetamine and phencyclidine. Based on animal model data, along with the finding that RASD2 influences prefronto-striatal phenotypes in healthy humans, we suggest that genetic mutation or reduced levels of this G-protein might have a role in cerebral circuitry dysfunction underpinning exaggerated psychotomimetic drugs responses and development of specific biological phenotypes linked to schizophrenia. PMID:26228524

Gap-prepulse inhibition of the startle reflex (GPIAS for tinnitus assessment: current status and future directions

Directory of Open Access Journals (Sweden)

Alexander eGalazyuk

2015-04-01

Full Text Available The progress in the field of tinnitus largely depends on the development of a reliable tinnitus animal model. Recently a new method based on the acoustic startle reflex modification was introduced for tinnitus screening in laboratory animals. This method was enthusiastically adopted and now widely used by many scientists in the field due to its seeming simplicity and a number of advantages over the other methods of tinnitus assessment. Furthermore, this method opened an opportunity for tinnitus assessment in humans as well. Unfortunately multiple modifications of data collection and interpretation implemented in different labs make comparisons across studies very difficult. In addition, recent animal and human studies have challenged the original filling-in interpretation of the paradigm. Here we review the current literature to emphasize on the commonalities and differences in data collection and interpretation across laboratories that are using this method for tinnitus assessment. We also propose future research directions that could be taken in order to establish whether or not this method is warranted as an indicator of the presence of tinnitus.

Music processing in preterm and full-term newborns: A psychophysiological interaction (PPI) approach in neonatal fMRI.

Science.gov (United States)

Lordier, Lara; Loukas, Serafeim; Grouiller, Frédéric; Vollenweider, Andreas; Vasung, Lana; Meskaldij, Djalel-Eddine; Lejeune, Fleur; Pittet, Marie Pascale; Borradori-Tolsa, Cristina; Lazeyras, François; Grandjean, Didier; Van De Ville, Dimitri; Hüppi, Petra S

2018-04-06

Neonatal Intensive Care Units (NICU) provide special equipment designed to give life support for the increasing number of prematurely born infants and assure their survival. More recently NICU's strive to include developmentally oriented care and modulate sensory input for preterm infants. Music, among other sensory stimuli, has been introduced into NICUs, but without knowledge on the basic music processing in the brain of preterm infants. In this study, we explored the cortico-subcortical music processing of different types of conditions (Original music, Tempo modification, Key transposition) in newborns shortly after birth to assess the effective connectivity of the primary auditory cortex with the entire newborn brain. Additionally, we investigated if early exposure during NICU stay modulates brain processing of music in preterm infants at term equivalent age. We approached these two questions using Psychophysiological Interaction (PPI) analyses. A group of preterm infants listened to music (Original music) starting from 33 weeks postconceptional age until term equivalent age and were compared to two additional groups without music intervention; preterm infants and full-term newborns. Auditory cortex functional connectivity with cerebral regions known to be implicated in tempo and familiarity processing were identified only for preterm infants with music training in the NICU. Increased connectivity between auditory cortices and thalamus and dorsal striatum may not only reflect their sensitivity to the known music and the processing of its tempo as familiar, but these results are also compatible with the hypothesis that the previously listened music induces a more arousing and pleasant state. Our results suggest that music exposure in NICU's environment can induce brain functional connectivity changes that are associated with music processing. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Buspirone Counteracts MK-801-Induced Schizophrenia-Like Phenotypes through Dopamine D3 Receptor Blockade

Science.gov (United States)

Torrisi, Sebastiano Alfio; Salomone, Salvatore; Geraci, Federica; Caraci, Filippo; Bucolo, Claudio; Drago, Filippo; Leggio, Gian Marco

2017-01-01

Background: Several efforts have been made to develop effective antipsychotic drugs. Currently, available antipsychotics are effective on positive symptoms, less on negative symptoms, but not on cognitive impairment, a clinically relevant dimension of schizophrenia. Drug repurposing offers great advantages over the long-lasting, risky and expensive, de novo drug discovery strategy. To our knowledge, the possible antipsychotic properties of buspirone, an azapirone anxiolytic drug marketed in 1986 as serotonin 5-HT1A receptor (5-HT1AR) partial agonist, have not been extensively investigated despite its intriguing pharmacodynamic profile, which includes dopamine D3 (D3R) and D4 receptor (D4R) antagonist activity. Multiple lines of evidence point to D3R as a valid therapeutic target for the treatment of several neuropsychiatric disorders including schizophrenia. In the present study, we tested the hypothesis that buspirone, behaving as dopamine D3R antagonist, may have antipsychotic-like activity. Materials and Methods: Effects of acute administration of buspirone was assessed on a wide-range of schizophrenia-relevant abnormalities induced by a single administration of the non-competitive NMDAR antagonist MK-801, in both wild-type mice (WT) and D3R-null mutant mice (D3R-/-). Results: Buspirone (3 mg⋅kg-1, i.p.) was devoid of cataleptogenic activity in itself, but resulted effective in counteracting disruption of prepulse inhibition (PPI), hyperlocomotion and deficit of temporal order recognition memory (TOR) induced by MK-801 (0.1 mg⋅kg-1, i.p.) in WT mice. Conversely, in D3R-/- mice, buspirone was ineffective in preventing MK-801-induced TOR deficit and it was only partially effective in blocking MK-801-stimulated hyperlocomotion. Conclusion: Taken together, these results indicate, for the first time, that buspirone, might be a potential therapeutic medication for the treatment of schizophrenia. In particular, buspirone, through its D3R antagonist activity, may be

Characteristics of soft x-ray and extreme ultraviolet (XUV) emission from laser-produced highly charged rhodium ions

Science.gov (United States)

Barte, Ellie Floyd; Hara, Hiroyuki; Tamura, Toshiki; Gisuji, Takuya; Chen, When-Bo; Lokasani, Ragava; Hatano, Tadashi; Ejima, Takeo; Jiang, Weihua; Suzuki, Chihiro; Li, Bowen; Dunne, Padraig; O'Sullivan, Gerry; Sasaki, Akira; Higashiguchi, Takeshi; Limpouch, Jiří

2018-05-01

We have characterized the soft x-ray and extreme ultraviolet (XUV) emission of rhodium (Rh) plasmas produced using dual pulse irradiation by 150-ps or 6-ns pre-pulses, followed by a 150-ps main pulse. We have studied the emission enhancement dependence on the inter-pulse time separation and found it to be very significant for time separations less than 10 ns between the two laser pulses when using 6-ns pre-pulses. The behavior using a 150-ps pre-pulse was consistent with such plasmas displaying only weak self-absorption effects in the expanding plasma. The results demonstrate the advantage of using dual pulse irradiation to produce the brighter plasmas required for XUV applications.

Mechanical and antibacterial properties of a nanocellulose-polypyrrole multilayer composite

Energy Technology Data Exchange (ETDEWEB)

Bideau, Benoit, E-mail: Benoit.bideau@uqtr.ca [Lignocellulosic Material Research Center, Université du Québec à Trois-Rivières, 3351 boul. des Forges, C.P. 500, Trois-Rivières, QC G9A 5H7 (Canada); Bras, Julien, E-mail: Julien.bras@pagora.grenoble-inp.fr [Univ. Grenoble Alpes, LGP2, F-38000 Grenoble (France); CNRS, LGP2, F-38000 Grenoble (France); Saini, Seema, E-mail: Seema.Saini@lgp2.grenoble-inp.fr [Univ. Grenoble Alpes, LGP2, F-38000 Grenoble (France); CNRS, LGP2, F-38000 Grenoble (France); Daneault, Claude, E-mail: Claude.daneault@uqtr.ca [Lignocellulosic Material Research Center, Université du Québec à Trois-Rivières, 3351 boul. des Forges, C.P. 500, Trois-Rivières, QC G9A 5H7 (Canada); Loranger, Eric, E-mail: Eric.Loranger1@uqtr.ca [Lignocellulosic Material Research Center, Université du Québec à Trois-Rivières, 3351 boul. des Forges, C.P. 500, Trois-Rivières, QC G9A 5H7 (Canada)

2016-12-01

In this study, a composite film based on TEMPO-oxidized cellulose nanofibers (TOCN), polyvinyl alcohol (PVA) and polypyrrole (PPy) was synthesized in situ by a chemical polymerization, resulting in the induced absorption of PPy on the surface of the TOCN. The composite films were investigated with scanning electron microscopy, thermogravimetric analysis, contact angle measurements, mechanical tests, and evaluation of antibacterial properties. The developed composite has nearly identical Young modulus (3.4 GPa), elongation (2.6%) and tensile stress (about 51 MPa) to TOCN even if PPy, which as poor properties by itself, was incorporated. From the energy-dispersive X-ray spectroscopy (EDX) results, it was shown that PPy is mainly located on the composite surface. Results confirmed by an increase from 54.5 to 83° in contact angle, an increased heat protection (Thermogravimetric analysis) and a decrease in surface energy. The nanocomposites were also evaluated for antibacterial activity against bacteria occasionally found in food: Gram-positive Bacillus subtilis (B. subtilis) and Gram-negative bacteria Escherichia coli (E. coli). The results indicate that the nanocomposites are effective against all of the bacteria studied as shown by the decrease of 5.2 log colony forming units (CFU) for B. subtilis and 6.5 log CFU for E. coli. Resulting in the total destruction of the studied bacteria. The perfect match between the resulting inhibition zone and the composite surface area has demonstrated that our composite was contact active with a slight leaching of PPy. Our composite was successful as an active packaging on meat (liver) as bacteria were killed by contact, thereby preventing the spread of possible diseases. While it has not been tested on bacteria found in medicine, TOCN/PVA-PPy film may be able to act as an active sterile packaging for surgical instruments. - Highlights: • Good antibacterial activity against Gram-positive and Gram-negative bacteria • High

A network-based predictive gene-expression signature for adjuvant chemotherapy benefit in stage II colorectal cancer.

Science.gov (United States)

Cao, Bangrong; Luo, Liping; Feng, Lin; Ma, Shiqi; Chen, Tingqing; Ren, Yuan; Zha, Xiao; Cheng, Shujun; Zhang, Kaitai; Chen, Changmin

2017-12-13

The clinical benefit of adjuvant chemotherapy for stage II colorectal cancer (CRC) is controversial. This study aimed to explore novel gene signature to predict outcome benefit of postoperative 5-Fu-based therapy in stage II CRC. Gene-expression profiles of stage II CRCs from two datasets with 5-Fu-based adjuvant chemotherapy (training dataset, n = 212; validation dataset, n = 85) were analyzed to identify the indicator. A systemic approach by integrating gene-expression and protein-protein interaction (PPI) network was implemented to develop the predictive signature. Kaplan-Meier curves and Cox proportional hazards model were used to determine the survival benefit of adjuvant chemotherapy. Experiments with shRNA knock-down were carried out to confirm the signature identified in this study. In the training dataset, we identified 44 PPI sub-modules, by which we separate patients into two clusters (1 and 2) having different chemotherapeutic benefit. A predictor of 11 PPI sub-modules (11-PPI-Mod) was established to discriminate the two sub-groups, with an overall accuracy of 90.1%. This signature was independently validated in an external validation dataset. Kaplan-Meier curves showed an improved outcome for patients who received adjuvant chemotherapy in Cluster 1 sub-group, but even worse survival for those in Cluster 2 sub-group. Similar results were found in both the training and the validation dataset. Multivariate Cox regression revealed an interaction effect between 11-PPI-Mod signature and adjuvant therapy treatment in the training dataset (RFS, p = 0.007; OS, p = 0.006) and the validation dataset (RFS, p = 0.002). From the signature, we found that PTGES gene was up-regulated in CRC cells which were more resistant to 5-Fu. Knock-down of PTGES indicated a growth inhibition and up-regulation of apoptotic markers induced by 5-Fu in CRC cells. Only a small proportion of stage II CRC patients could benefit from adjuvant therapy. The 11-PPI-Mod as

MHC class II-derived peptides can bind to class II molecules, including self molecules, and prevent antigen presentation

DEFF Research Database (Denmark)

Rosloniec, E F; Vitez, L J; Buus, S

1990-01-01

the alpha k-3 peptide binds slightly less well. These combined data, suggesting that class II-derived peptides can bind to MHC class II molecules, including the autologous molecule from which they are derived, have important implications for the molecular basis of alloreactivity and autoreactivity. Further...... found in the first and third polymorphic regions (PMR) of the A alpha k chain (alpha k-1 and alpha k-3) were capable of inhibiting the presentation of three different HEL-derived peptide antigens to their appropriate T cells. In addition, the alpha k-1 peptide inhibited the presentation of the OVA(323......-339) immunodominant peptide to the I-Ad-restricted T cell hybridomas specific for it. Prepulsing experiments demonstrated that the PMR peptides were interacting with the APC and not with the T cell hybridomas. These observations were confirmed and extended by the demonstration that the alpha k-1 and alpha k-3...

The Gap-Startle Paradigm for Tinnitus Screening in Animal Models: Limitations and Optimization

Science.gov (United States)

Lobarinas, Edward; Hayes, Sarah H.; Allman, Brian L.

2012-01-01

In 2006, Turner and colleagues (Behav Neurosci, 120:188–195) introduced the gap-startle paradigm as a high-throughput method for tinnitus screening in rats. Under this paradigm, gap detection ability was assessed by determining the level of inhibition of the acoustic startle reflex produced by a short silent gap inserted in an otherwise continuous background sound prior to a loud startling stimulus. Animals with tinnitus were expected to show impaired gap detection ability (i.e., lack of inhibition of the acoustic startle reflex) if the background sound containing the gap was qualitatively similar to the tinnitus pitch. Thus, for the gap-startle paradigm to be a valid tool to screen for tinnitus, a robust startle response from which to inhibit must be present. Because recent studies have demonstrated that the acoustic startle reflex could be dramatically reduced following noise exposure, we endeavored to 1) modify the gap-startle paradigm to be more resilient in the presence of hearing loss, and 2) evaluate whether a reduction in startle reactivity could confound the interpretation of gap prepulse inhibition and lead to errors in screening for tinnitus. In the first experiment, the traditional broadband noise (BBN) startle stimulus was replaced by a bandpass noise in which the sound energy was concentrated in the lower frequencies (5–10 kHz) in order to maintain audibility of the startle stimulus after unilateral high frequency noise exposure (16 kHz). However, rats still showed a 57% reduction in startle amplitude to the bandpass noise post-noise exposure. A follow-up experiment on a separate group of rats with transiently-induced conductive hearing loss revealed that startle reactivity was better preserved when the BBN startle stimulus was replaced by a rapid airpuff to the back of the rats neck. Furthermore, it was found that transient unilateral conductive hearing loss, which was not likely to induce tinnitus, caused an impairment in gap prepulse inhibition

Pulsed magnetization transfer contrast MRI by a sequence with water selective excitation

Energy Technology Data Exchange (ETDEWEB)

Schick, F. [Univ. of Tuebingen (Germany)

1996-01-01

A water selective SE imaging sequence was developed providing suitable properties for the assessment of magnetization transfer (MT) effects in tissues with considerable amounts of fat. The sequence with water selective excitation and slice selective refocusing combines the following features: The RIF exposure on the macromolecular protons is relatively low for single slice imaging without MT prepulses, since no additional pulses for fat saturation are necessary. Water selection by frequency selective excitation diminishes faults in the subtraction of images recorded with and without MT prepulses (which might arise from movements). High differences in the signal amplitudes from hyaline cartilage and muscle tissue were obtained comparing images recorded with irradiation of the series of prepulses for MT and those lacking MT prepulses. Utilizations of the described water selective approach for the assessment of MT effects in lesions of cartilage and bone are demonstrated. MT saturation was also examined in muscles with fatty degeneration of patients suffering from progressive muscular dystrophy. The described technique allows determination of MT effects with good precision in a single slice, especially in regions with dominating fat signals. 22 refs., 5 figs.

Hypoxia-induced hypothermia mediated by GABA in the rostral parapyramidal area of the medulla oblongata.

Science.gov (United States)

Osaka, T

2014-05-16

Hypoxia evokes a regulated decrease in the body core temperature (Tc) in a variety of animals. The neuronal mechanisms of this response include, at least in part, glutamatergic activation in the lateral preoptic area (LPO) of the hypothalamus. As the sympathetic premotor neurons in the medulla oblongata constitute a cardinal relay station in the descending neuronal pathway from the hypothalamus for thermoregulation, their inhibition can also be critically involved in the mechanisms of the hypoxia-induced hypothermia. Here, I examined the hypothesis that hypoxia-induced hypothermia is mediated by glutamate-responsive neurons in the LPO that activate GABAergic transmission in the rostral raphe pallidus (rRPa) and neighboring parapyramidal region (PPy) of the medulla oblongata in urethane-chloralose-anesthetized, neuromuscularly blocked, artificially ventilated rats. Unilateral microinjection of GABA (15nmol) into the rRPa and PPy regions elicited a prompt increase in tail skin temperature (Ts) and decreases in Tc, oxygen consumption rate (VO2), and heart rate. Next, when the GABAA receptor blocker bicuculline methiodide (bicuculline methiodide (BMI), 10pmol) alone was microinjected into the rRPa, it elicited unexpected contradictory responses: simultaneous increases in Ts, VO2 and heart rate and a decrease in Tc. Then, when BMI was microinjected bilaterally into the PPy, no direct effect on Ts was seen; and thermogenic and tachycardic responses were slight. However, pretreatment of the PPy with BMI, but not vehicle saline, greatly attenuated the hypothermic responses evoked by hypoxic (10%O2-90%N2, 5min) ventilation or bilateral microinjections of glutamate (5nmol, each side) into the LPO. The results suggest that hypoxia-induced hypothermia was mediated, at least in part, by the activation of GABAA receptors in the PPy. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

The extent, quality and impact of patient and public involvement in primary care research: a mixed methods study.

Science.gov (United States)

Blackburn, Steven; McLachlan, Sarah; Jowett, Sue; Kinghorn, Philip; Gill, Paramjit; Higginbottom, Adele; Rhodes, Carol; Stevenson, Fiona; Jinks, Clare

2018-01-01

In the UK, more patients go to primary care than other parts of the health service. Therefore it is important for research into primary care to include the insights and views of people who receive these services. To explore the extent, quality and impact of patient and public involvement (PPI) in primary care research, we examined documents of 200 projects and surveyed 191 researchers.We found that about half of studies included PPI to develop research ideas and during the study itself. Common activities included designing study materials, advising on methods, and managing the research. Some studies did not undertake the PPI activities initially planned and funded for. PPI varied by study design, health condition and study population. We found pockets of good practice: having a PPI budget, supporting PPI contributors, and PPI informing recruitment issues. However, good practice was lacking in other areas. Few projects offered PPI contributors training, used PPI to develop information for participants about study progress and included PPI to advise on publishing findings.Researchers reported beneficial impacts of PPI. Most impact was reported when the approach to PPI included more indicators of good practice. The main cost of PPI for researchers was their time. Many reported difficulties providing information about PPI.In partnership with PPI contributors, we have used these findings to develop:a new Cost and Consequences Framework for PPI highlighting financial and non-financial costs, benefits and harms of PPIFifteen co-produced recommendations to improve the practice and delivery of PPI. Background: To improve the lives of patients in primary care requires the involvement of service users in primary care research. We aimed to explore the extent, quality and impact of patient and public involvement (PPI) in primary care research. Methods: We extracted information about PPI from grant applications, reports and an electronic survey of researchers of studies funded

Proactive modulation of long-interval intracortical inhibition during response inhibition

Science.gov (United States)

Cowie, Matthew J.; MacDonald, Hayley J.; Cirillo, John

2016-01-01

Daily activities often require sudden cancellation of preplanned movement, termed response inhibition. When only a subcomponent of a whole response must be suppressed (required here on Partial trials), the ensuing component is markedly delayed. The neural mechanisms underlying partial response inhibition remain unclear. We hypothesized that Partial trials would be associated with nonselective corticomotor suppression and that GABAB receptor-mediated inhibition within primary motor cortex might be responsible for the nonselective corticomotor suppression contributing to Partial trial response delays. Sixteen right-handed participants performed a bimanual anticipatory response inhibition task while single- and paired-pulse transcranial magnetic stimulation was delivered to elicit motor evoked potentials in the left first dorsal interosseous muscle. Lift times, amplitude of motor evoked potentials, and long-interval intracortical inhibition were examined across the different trial types (Go, Stop-Left, Stop-Right, Stop-Both). Go trials produced a tight distribution of lift times around the target, whereas those during Partial trials (Stop-Left and Stop-Right) were substantially delayed. The modulation of motor evoked potential amplitude during Stop-Right trials reflected anticipation, suppression, and subsequent reinitiation of movement. Importantly, suppression was present across all Stop trial types, indicative of a “default” nonselective inhibitory process. Compared with blocks containing only Go trials, inhibition increased when Stop trials were introduced but did not differ between trial types. The amount of inhibition was positively correlated with lift times during Stop-Right trials. Tonic levels of inhibition appear to be proactively modulated by task context and influence the speed at which unimanual responses occur after a nonselective “brake” is applied. PMID:27281744

Amplification of spontaneous emission of neon-like argon in a fast gas-filled capillary discharge

International Nuclear Information System (INIS)

Kolacek, K.; Schmidt, J.; Bohacek, V.; Ripa, M.; Frolov, O.; Vrba, P.; Straus, J.; Prukner, V.; Rupasov, A. A.; Shikanov, A. S.

2008-01-01

The evolution of the CAPEX facility and its basic diagnostics are described. The experiments carried out in the last modification of this facility accomplished with the demonstration of amplified spontaneous emission of neon-like argon (Ar 8+ ) at the wavelength 46.88 nm. The first version of the facility, CAPEX1, operated with a plastic capillary and had a short high-power passive prepulse and an imperfect gas-filling system. In the second version, CAPEX2, a ceramic capillary was used, the prepulse amplitude was lowered, and the gas-filling system was improved. In the third, most successful version, CAPEX3, the capillary bending was reduced, a longer external prepulse was used, and the gas-filling system was further optimized. For each version, results of X-ray measurements are presented and interpreted

Identification of Small Molecule Translesion Synthesis Inhibitors That Target the Rev1-CT/RIR Protein-Protein Interaction.

Science.gov (United States)

Sail, Vibhavari; Rizzo, Alessandro A; Chatterjee, Nimrat; Dash, Radha C; Ozen, Zuleyha; Walker, Graham C; Korzhnev, Dmitry M; Hadden, M Kyle

2017-07-21

Translesion synthesis (TLS) is an important mechanism through which proliferating cells tolerate DNA damage during replication. The mutagenic Rev1/Polζ-dependent branch of TLS helps cancer cells survive first-line genotoxic chemotherapy and introduces mutations that can contribute to the acquired resistance so often observed with standard anticancer regimens. As such, inhibition of Rev1/Polζ-dependent TLS has recently emerged as a strategy to enhance the efficacy of first-line chemotherapy and reduce the acquisition of chemoresistance by decreasing tumor mutation rate. The TLS DNA polymerase Rev1 serves as an integral scaffolding protein that mediates the assembly of the active multiprotein TLS complexes. Protein-protein interactions (PPIs) between the C-terminal domain of Rev1 (Rev1-CT) and the Rev1-interacting region (RIR) of other TLS DNA polymerases play an essential role in regulating TLS activity. To probe whether disrupting the Rev1-CT/RIR PPI is a valid approach for developing a new class of targeted anticancer agents, we designed a fluorescence polarization-based assay that was utilized in a pilot screen for small molecule inhibitors of this PPI. Two small molecule scaffolds that disrupt this interaction were identified, and secondary validation assays confirmed that compound 5 binds to Rev1-CT at the RIR interface. Finally, survival and mutagenesis assays in mouse embryonic fibroblasts and human fibrosarcoma HT1080 cells treated with cisplatin and ultraviolet light indicate that these compounds inhibit mutagenic Rev1/Polζ-dependent TLS in cells, validating the Rev1-CT/RIR PPI for future anticancer drug discovery and identifying the first small molecule inhibitors of TLS that target Rev1-CT.

  A Cost-Effectiveness Analysis of Two Management Strategies for Dyspepsia

DEFF Research Database (Denmark)

Kjeldsen, Hans Chr; Bech, Mickael; Christensen, Bo

2007-01-01

Objectives: To compare the cost-effectiveness of endoscopy and empirical proton pump inhibition (PPI) therapy for management of dyspepsia in primary care. Methods: A randomized controlled trial (RCT) including prospective collection of economic resource data was conducted in general practice from...... of dyspeptic symptoms and proportion of patients with dyspepsia after one year based on patients' and general practitioners' (GPs') assessment. Costs were estimated from patient and GP questionnaires and from medical records. Results: The incremental cost-effectiveness (CE) ratio for one day free of dyspeptic...... symptoms using the endoscopy strategy was €/day 154 compared with the PPI strategy. The incremental CE ratio for one person free of dyspeptic symptoms after one year using the endoscopy strategy was € 13,905 based on the patients' evaluation and the incremental CE ratio for one person free of predominant...

Interactions of Stress and Nicotine on Amplitude, Pre-Pulse Inhibition and Habituation of the Acoustic Startle Reflex

Science.gov (United States)

1992-09-24

Marquez , Armario , & Gelpi, 1988) consistent with a stress response . Restraint stress has been reported to increase the amplitude of sensory...and NE in the brain (Adell , Garcia- Marquez , Armario , & Gelpi , 1988) consistent with a stress response. Restraint stress has been reported t o...and non- reactive strains. Al coholism. Clinical and Experimental Research, ~(2), 170-174. Adell, A., Garcia - Marquez, C., Armario , A. , & Gelpi , E

Tcf4 Regulates Synaptic Plasticity, DNA Methylation, and Memory Function

Directory of Open Access Journals (Sweden)

Andrew J. Kennedy

2016-09-01

Full Text Available Human haploinsufficiency of the transcription factor Tcf4 leads to a rare autism spectrum disorder called Pitt-Hopkins syndrome (PTHS, which is associated with severe language impairment and development delay. Here, we demonstrate that Tcf4 haploinsufficient mice have deficits in social interaction, ultrasonic vocalization, prepulse inhibition, and spatial and associative learning and memory. Despite learning deficits, Tcf4(+/− mice have enhanced long-term potentiation in the CA1 area of the hippocampus. In translationally oriented studies, we found that small-molecule HDAC inhibitors normalized hippocampal LTP and memory recall. A comprehensive set of next-generation sequencing experiments of hippocampal mRNA and methylated DNA isolated from Tcf4-deficient and WT mice before or shortly after experiential learning, with or without administration of vorinostat, identified “memory-associated” genes modulated by HDAC inhibition and dysregulated by Tcf4 haploinsufficiency. Finally, we observed that Hdac2 isoform-selective knockdown was sufficient to rescue memory deficits in Tcf4(+/− mice.

Preparation and microwave absorbing properties of nickel-coated graphite nanosheet with pyrrole via in situ polymerization

International Nuclear Information System (INIS)

Yang Yongqing; Qi Shuhua; Wang Jianning

2012-01-01

Highlights: ► NanoG was prepared and chemically coated by nano-Ni. ► PPy/NanoG and PPy/Ni/NanoG were prepared via in situ polymerization. ► The samples were characterized by SEM, XRD, EDS and FTIR. ► PPy/NanoG and PPy/Ni/NanoG exhibit good electromagnetic properties. - Abstract: Nanocomposites PPy/NanoG and PPy/Ni/NanoG were prepared via in situ polymerization of pyrrole in the presence of NanoG and nickel-coated graphite nanosheet (Ni/NanoG), respectively. The morphologies and nanostructures of NanoG, Ni/NanoG, PPy, PPy/NanoG and PPy/Ni/NanoG were characterized by scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), Fourier transmission infrared (FTIR) and X-ray diffraction analysis (XRD). Results show that most of PPy chains disperse on NanoG and Ni/NanoG's surfaces for the high aspect ratio (300–500) of NanoG and Ni/NanoG. From the thermogravimetric analysis (TG) it can be seen that the introduction of Ni and NanoG leads the composites PPy/NanoG and PPy/Ni/NanoG to exhibit a better thermal stability than pure PPy. According to the four-point-probe test, the conductivities of the final PPy/NanoG and PPy/Ni/NanoG composites are dramatically increased compared to pure PPy. Measurement of electromagnetic parameters shows that the reflection loss (R) of PPy/Ni/NanoG is below −19 dB at the X band (8.2–12.4 GHz) and the minimum loss value is −23.46 dB at 9.88 GHz. The reflection loss of PPy/NanoG is below −10 dB at 8.2–12.4 GHz and the minimum loss value is −13.44 dB at 10.28 GHz. The microwave absorbing properties of PPy/NanoG and PPy/Ni/NanoG are superior to those of PPy.

Effect of Qufengtongluo Decoction on PI3K/Akt Signaling Pathway in the Kidney of Type 2 Diabetes Mellitus Rat (GK Rat with Diabetic Nephropathy

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Wei-Jun Huang

2018-01-01

Full Text Available Qufengtongluo (QFTL decoction is an effective treatment for diabetic nephropathy (DN. However, the underlying molecular mechanism is still unclear. In this study, we try to investigate whether QFTL decoction acts via inhibiting PI3K/Akt signaling pathway. Twenty-four GK rats were randomly divided into 3 groups: blank group, sham-operated group, and QFTL group. After model establishment, rats in QFTL group were given QFTL decoction by gavage, while the rest were given pure water. During the 8-week intervention, 24 hr urinal protein was measured every 2-3 weeks. After intervention, kidneys were removed for pathological smear, quantitative real-time PCR, and western blotting to detect expression levels of p-PI3K, p-Akt, PTEN, TGF-β, PI3K mRNA, Akt mRNA, PTEN mRNA, and TGF-β mRNA. QFTL group showed a slighter degree of renal fibrosis in Masson and PASM staining and a greater reduction of 24 hr urinal protein than blank group. Compared to blank group, expression levels of p-PI3K, p-Akt, PI3K mRNA, and Akt mRNA were lower in QFTL group, while expression levels of PTEN and PTEN mRNA were higher. Besides, TGF-β was downregulated by QFTL decoction. In conclusion, this study suggests that QFTL decoction might inhibit PI3K/Akt signaling pathway via activating PTEN and inhibiting TGF-β.

INHIBITION IN SPEAKING PERFORMANCE

OpenAIRE

Humaera, Isna

2015-01-01

The most common problem encountered by the learner in the languageacquisition process is learner inhibition. Inhibition refers to a temperamentaltendency to display wariness, fearfulness, or restrain in response tounfamiliar people, objects, and situations. There are some factors that causeinhibition, such as lack of motivation, shyness, self-confidence, self-esteem,and language ego. There are also levels of inhibition, it refers to kinds ofinhibition and caused of inhibition itself. Teacher ...

AlphaSpace: Fragment-Centric Topographical Mapping To Target Protein–Protein Interaction Interfaces

Science.gov (United States)

2016-01-01

Inhibition of protein–protein interactions (PPIs) is emerging as a promising therapeutic strategy despite the difficulty in targeting such interfaces with drug-like small molecules. PPIs generally feature large and flat binding surfaces as compared to typical drug targets. These features pose a challenge for structural characterization of the surface using geometry-based pocket-detection methods. An attractive mapping strategy—that builds on the principles of fragment-based drug discovery (FBDD)—is to detect the fragment-centric modularity at the protein surface and then characterize the large PPI interface as a set of localized, fragment-targetable interaction regions. Here, we introduce AlphaSpace, a computational analysis tool designed for fragment-centric topographical mapping (FCTM) of PPI interfaces. Our approach uses the alpha sphere construct, a geometric feature of a protein’s Voronoi diagram, to map out concave interaction space at the protein surface. We introduce two new features—alpha-atom and alpha-space—and the concept of the alpha-atom/alpha-space pair to rank pockets for fragment-targetability and to facilitate the evaluation of pocket/fragment complementarity. The resulting high-resolution interfacial map of targetable pocket space can be used to guide the rational design and optimization of small molecule or biomimetic PPI inhibitors. PMID:26225450

Understanding of electrochemical and structural changes of polypyrrole/polyethylene glycol composite films in aqueous solution

Energy Technology Data Exchange (ETDEWEB)

Pirvu, Cristian, E-mail: c_pirvu@chim.pub.ro [University Polytechnic of Bucharest, Faculty of Applied Chemistry and Materials Science, 1-7 Polizu, 011061 Bucharest (Romania); Manole, Claudiu Constantin; Stoian, Andrei Bogdan; Demetrescu, Ioana [University Polytechnic of Bucharest, Faculty of Applied Chemistry and Materials Science, 1-7 Polizu, 011061 Bucharest (Romania)

2011-11-30

Highlights: > Electrochemical monitoring of PPy and PPy-PEG films over immersion time. > Electrochemical and surface analysis showed that PEG improves the stability of PPy films. > Mott-Schottky analysis reveals p-type conductance for both films. > In situ AFM analysis sustains electrochemical behaviour. > A model of PPy and PPy-PEG films behaviour during immersion was elaborated. - Abstract: Electrochemical monitoring of electrical and structural changes of both PPy and PPy-PEG films electrochemical deposited, in order to highlight if the structural stability offered by PEG has an influence on electrical properties and stability in aqueous solution over immersion time was investigated. Electrochemical analysis suggests that PPy-PEG film inserts cations easier than PPy film for a short immersion time probably due to ability of PEG to form complexes with metal cations. The FTIR spectra showed that the PEG incorporation decreases the rate of PPy overoxidation probably by restraining the electron release and by rendering O{sub 2} inaccessible to PPy. Mott-Schottky analysis based on capacitance measurement reveal p-type conductance for both films. The in situ AFM analysis sustains electrochemical behaviour and has permitted elaboration of a model of PPy and PPy-PEG films behaviour during immersion in testing solution.

Inhibition of lactation.

Science.gov (United States)

Llewellyn-Jones, D

1975-01-01

The mechanism and hormonal regulation of lactation is explained and illustrated with a schematic representation. Circulating estrogen above a critical amount seems to be the inhibitory factor controlling lactation during pregnancy. Once delivery occurs, the level of estrogen falls, that of prolactin rises, and lactation begins. Nonsuckling can be used to inhibit lactation. Estrogens can also be used to inhibit lactation more quickly and with less pain. The reported association between estrogens and puerperal thromboembolism cannot be considered conclusive due to defects in the reporting studies. There is no reason not to use estrogens in lactation inhibition except for women over 35 who experienced a surgical delivery. Alternative therapy is available for these women. The recently-developed drug, brom-ergocryptine, may replace other methods of lactation inhibition.

Chondroitin sulphate-guided construction of polypyrrole nanoarchitectures

Energy Technology Data Exchange (ETDEWEB)

Zhou, Zhengnan [School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641 (China); Zhu, Wenjun [Department of Prosthodontics, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Liao, Jingwen [School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641 (China); Huang, Shishu [State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University (China); Department of Orthopaedics and Traumatology, The University of Hong Kong (China); Chen, Junqi; He, Tianrui [School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641 (China); Tan, Guoxin, E-mail: tanguoxin@126.com [Faculty of Light and Chemical, Guangdong University of Technology, Guangzhou 510006 (China); Ning, Chengyun, E-mail: imcyning@scut.edu.cn [School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641 (China)

2015-03-01

Nanospheres, nanocones, and nanowires are three typical polypyrrole (PPy) nanoarchitectures and electrochemically polymerized with the dope of chondroitin sulphate (CS) in this study. CS, a functional biomacromolecule, guides the formation of PPy nanoarchitectures as the dopant and morphology-directing agent. Combined with our previous reported other PPy nanoarchitectures (such as nanotube arrays and nanowires), this work further proposed the novel mechanism of the construction of PPy/CS nanoarchitectures with the synergistic effect of CS molecular chains structure and the steric hindrance. Compared to the undoped PPy, MC3T3-E1 cells with PPy/CS nanoarchitectures possessed stronger proliferation and osteogenic differentiation capability. This suggests that PPy/CS nanoarchitectures have appropriate biocompatibility. Altogether, the nanoarchitectured PPy/CS may find application in the regeneration of bone defect. - Highlights: • The formation mechanism of PPy nanoarchitectures was proposed. • CS acted as biofunctional dopant and morphology-directing agent in PPy forming. • PPy-CS nanoarchitectures were dependent on the Py/CS ratio.

Understanding of electrochemical and structural changes of polypyrrole/polyethylene glycol composite films in aqueous solution

International Nuclear Information System (INIS)

Pirvu, Cristian; Manole, Claudiu Constantin; Stoian, Andrei Bogdan; Demetrescu, Ioana

2011-01-01

Highlights: → Electrochemical monitoring of PPy and PPy-PEG films over immersion time. → Electrochemical and surface analysis showed that PEG improves the stability of PPy films. → Mott-Schottky analysis reveals p-type conductance for both films. → In situ AFM analysis sustains electrochemical behaviour. → A model of PPy and PPy-PEG films behaviour during immersion was elaborated. - Abstract: Electrochemical monitoring of electrical and structural changes of both PPy and PPy-PEG films electrochemical deposited, in order to highlight if the structural stability offered by PEG has an influence on electrical properties and stability in aqueous solution over immersion time was investigated. Electrochemical analysis suggests that PPy-PEG film inserts cations easier than PPy film for a short immersion time probably due to ability of PEG to form complexes with metal cations. The FTIR spectra showed that the PEG incorporation decreases the rate of PPy overoxidation probably by restraining the electron release and by rendering O 2 inaccessible to PPy. Mott-Schottky analysis based on capacitance measurement reveal p-type conductance for both films. The in situ AFM analysis sustains electrochemical behaviour and has permitted elaboration of a model of PPy and PPy-PEG films behaviour during immersion in testing solution.

Proton pump inhibition and cancer therapeutics: A specific tumor targeting or it is a phenomenon secondary to a systemic buffering?

Science.gov (United States)

Spugnini, Enrico; Fais, Stefano

2017-04-01

One of the unsolved mysteries in oncology includes the strategies that cancer cells adopt to cope with an adverse microenvironment. However, we knew, from the Warburg's discovery that through their metabolism based on sugar fermentation, cancer cells acidify their microenvironment and this progressive acidification induces a selective pressure, leading to the development of very malignant cells entirely armed to survive in the hostile microenvironment generated by their own metabolism. In the last decades a primordial role for proton exchangers has been supported as a key tumor advantage in facing off the acidic milieu. Proton exchangers do not allow intracellular acidification through a continuous elimination of H+ either outside the cells or within the internal vacuoles. This article wants to comment a translational process through that led to the preclinical demonstration that a class of proton pump inhibitors (PPI) exploited worldwide for peptic ulcer treatment and gastroprotection are indeed powerful chemosensitizers as well. In this process we achieved the clinical proof of concept that PPI may well be included in new anti-cancer strategies with a solid background and rationale. Copyright © 2017 Elsevier Ltd. All rights reserved.

The influence of laser-particle interaction in laser induced breakdown spectroscopy and laser ablation inductively coupled plasma spectrometry

International Nuclear Information System (INIS)

Lindner, Helmut; Loper, Kristofer H.; Hahn, David W.; Niemax, Kay

2011-01-01

Particles produced by previous laser shots may have significant influence on the analytical signal in laser-induced breakdown spectroscopy (LIBS) and laser ablation inductively coupled plasma (LA-ICP) spectrometry if they remain close to the position of laser sampling. The effects of these particles on the laser-induced breakdown event are demonstrated in several ways. LIBS-experiments were conducted in an ablation cell at atmospheric conditions in argon or air applying a dual-pulse arrangement with orthogonal pre-pulse, i.e., plasma breakdown in a gas generated by a focussed laser beam parallel and close to the sample surface followed by a delayed crossing laser pulse in orthogonal direction which actually ablates material from the sample and produces the LIBS plasma. The optical emission of the LIBS plasma as well as the absorption of the pre-pulse laser was measured. In the presence of particles in the focus of the pre-pulse laser, the plasma breakdown is affected and more energy of the pre-pulse laser is absorbed than without particles. As a result, the analyte line emission from the LIBS plasma of the second laser is enhanced. It is assumed that the enhancement is not only due to an increase of mass ablated by the second laser but also to better atomization and excitation conditions favored by a reduced gas density in the pre-pulse plasma. Higher laser pulse frequencies increase the probability of particle-laser interaction and, therefore, reduce the shot-to-shot line intensity variation as compared to lower particle loadings in the cell. Additional experiments using an aerosol chamber were performed to further quantify the laser absorption by the plasma in dependence on time both with and without the presence of particles. The overall implication of laser-particle interactions for LIBS and LA-ICP-MS/OES are discussed.

The influence of laser-particle interaction in laser induced breakdown spectroscopy and laser ablation inductively coupled plasma spectrometry

Science.gov (United States)

Lindner, Helmut; Loper, Kristofer H.; Hahn, David W.; Niemax, Kay

2011-02-01

Particles produced by previous laser shots may have significant influence on the analytical signal in laser-induced breakdown spectroscopy (LIBS) and laser ablation inductively coupled plasma (LA-ICP) spectrometry if they remain close to the position of laser sampling. The effects of these particles on the laser-induced breakdown event are demonstrated in several ways. LIBS-experiments were conducted in an ablation cell at atmospheric conditions in argon or air applying a dual-pulse arrangement with orthogonal pre-pulse, i.e., plasma breakdown in a gas generated by a focussed laser beam parallel and close to the sample surface followed by a delayed crossing laser pulse in orthogonal direction which actually ablates material from the sample and produces the LIBS plasma. The optical emission of the LIBS plasma as well as the absorption of the pre-pulse laser was measured. In the presence of particles in the focus of the pre-pulse laser, the plasma breakdown is affected and more energy of the pre-pulse laser is absorbed than without particles. As a result, the analyte line emission from the LIBS plasma of the second laser is enhanced. It is assumed that the enhancement is not only due to an increase of mass ablated by the second laser but also to better atomization and excitation conditions favored by a reduced gas density in the pre-pulse plasma. Higher laser pulse frequencies increase the probability of particle-laser interaction and, therefore, reduce the shot-to-shot line intensity variation as compared to lower particle loadings in the cell. Additional experiments using an aerosol chamber were performed to further quantify the laser absorption by the plasma in dependence on time both with and without the presence of particles. The overall implication of laser-particle interactions for LIBS and LA-ICP-MS/OES are discussed.

Influence of pea protein aggregates on the structure and stability of pea protein/soybean polysaccharide complex emulsions.

Science.gov (United States)

Yin, Baoru; Zhang, Rujing; Yao, Ping

2015-03-20

The applications of plant proteins in the food and beverage industry have been hampered by their precipitation in acidic solution. In this study, pea protein isolate (PPI) with poor dispersibility in acidic solution was used to form complexes with soybean soluble polysaccharide (SSPS), and the effects of PPI aggregates on the structure and stability of PPI/SSPS complex emulsions were investigated. Under acidic conditions, high pressure homogenization disrupts the PPI aggregates and the electrostatic attraction between PPI and SSPS facilitates the formation of dispersible PPI/SSPS complexes. The PPI/SSPS complex emulsions prepared from the PPI containing aggregates prove to possess similar droplet structure and similar stability compared with the PPI/SSPS emulsions produced from the PPI in which the aggregates have been previously removed by centrifugation. The oil droplets are protected by PPI/SSPS complex interfacial films and SSPS surfaces. The emulsions show long-term stability against pH and NaCl concentration changes. This study demonstrates that PPI aggregates can also be used to produce stable complex emulsions, which may promote the applications of plant proteins in the food and beverage industry.

Influence of Pea Protein Aggregates on the Structure and Stability of Pea Protein/Soybean Polysaccharide Complex Emulsions

Directory of Open Access Journals (Sweden)

Baoru Yin

2015-03-01

Full Text Available The applications of plant proteins in the food and beverage industry have been hampered by their precipitation in acidic solution. In this study, pea protein isolate (PPI with poor dispersibility in acidic solution was used to form complexes with soybean soluble polysaccharide (SSPS, and the effects of PPI aggregates on the structure and stability of PPI/SSPS complex emulsions were investigated. Under acidic conditions, high pressure homogenization disrupts the PPI aggregates and the electrostatic attraction between PPI and SSPS facilitates the formation of dispersible PPI/SSPS complexes. The PPI/SSPS complex emulsions prepared from the PPI containing aggregates prove to possess similar droplet structure and similar stability compared with the PPI/SSPS emulsions produced from the PPI in which the aggregates have been previously removed by centrifugation. The oil droplets are protected by PPI/SSPS complex interfacial films and SSPS surfaces. The emulsions show long-term stability against pH and NaCl concentration changes. This study demonstrates that PPI aggregates can also be used to produce stable complex emulsions, which may promote the applications of plant proteins in the food and beverage industry.

Should we stop thinking about inhibition? Searching for individual and age differences in inhibition ability.

Science.gov (United States)

Rey-Mermet, Alodie; Gade, Miriam; Oberauer, Klaus

2018-04-01

Inhibition is often conceptualized as a unitary construct reflecting the ability to ignore and suppress irrelevant information. At the same time, it has been subdivided into inhibition of prepotent responses (i.e., the ability to stop dominant responses) and resistance to distracter interference (i.e., the ability to ignore distracting information). The present study investigated the unity and diversity of inhibition as a psychometric construct, and tested the hypothesis of an inhibition deficit in older age. We measured inhibition in young and old adults with 11 established laboratory tasks: antisaccade, stop-signal, color Stroop, number Stroop, arrow flanker, letter flanker, Simon, global-local, positive and negative compatibility tasks, and n-2 repetition costs in task switching. In both age groups, the inhibition measures from individual tasks had good reliabilities, but correlated only weakly among each other. Structural equation modeling identified a 2-factor model with factors for inhibition of prepotent responses and resistance to distracter interference. Older adults scored worse in the inhibition of prepotent response, but better in the resistance to distracter interference. However, the model had low explanatory power. Together, these findings call into question inhibition as a psychometric construct and the hypothesis of an inhibition deficit in older age. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Electrochemical synthesis of highly ordered polypyrrole on copper modified aluminium substrates

International Nuclear Information System (INIS)

Siddaramanna, Ashoka; Saleema, N.; Sarkar, D.K.

2014-01-01

Fabrication of highly ordered conducting polymers on metal surfaces has received a significant interest owing to their potential applications in organic electronic devices. In this context, we have developed a simple method for the synthesis of highly ordered polypyrrole (PPy) on copper modified aluminium surfaces via electrochemical polymerization process. A series of characteristic peaks of PPy evidenced on the infrared spectra of these surfaces confirm the formation of PPy. The X-ray diffraction (XRD) pattern of PPy deposited on copper modified aluminium surfaces also confirmed the deposition of PPy as a sharp and intense peak at 2θ angle of 23° attributable to PPy is observed while this peak is absent on PPy deposited on as-received aluminium surfaces. An atomic model of the interface of PPy/Cu has been presented based on the inter-atomic distance of copper–copper of (1 0 0) plane and the inter-monomer distance of PPy, to describe the ordering of PPy on Cu modified Al surfaces.

USE OF WOOD DERIVATIVES AS DOPING / DISPERSING AGENTS IN THE PREPARATION OF POLYPYRROLE AQUEOUS DISPERSIONS

Directory of Open Access Journals (Sweden)

Claudia Sasso

2008-11-01

Full Text Available Polystyrene sulfonic acid (PSS, lignosulfonic acid (LS sodium salts, and carboxymethylcellulose (CMC were used as doping/dispersing agents in the chemical polymerization of polypyrrole (Ppy. Conductivity measure-ments performed on dry Ppy pellets showed a sharp increase in conductivity when adding the anionic polymers to the polymerization liquor. For a polyanion/pyrrole weight ratio ranging between 0.1 and 0.6, the highest conductivity was given by PpyCMC (82 S/m and PpyPSS (80 S/m, followed by PpyLS (6 S/m. On the other hand, for a polyanion/pyrrole ratio higher than 0.6, the conductivity of PpyPSS systems sharply decreased, and for polyanion/pyrrole ratios higher than 1, the highest conductivity was given by PpyCMC (~10 S/m, followed by PpyLS (~7 S/m and PpyPSS (~5 S/m. Zeta-potential measurements showed that the surface charge of Ppy was strongly affected by the polyanion type and amount. Cationic Ppy particles were obtained in the presence of the two polymers bearing strongly acidic moieties (PSS and LS. Anionic PpyPSS colloids were obtained at the highest PSS/Py ratio, after the degradation of the conducting properties. When using a weakly acidic dopant (CMC, PpyCMC colloids had a negative charge for all of the tested conditions.

Controlled delivery of Gemcitabine Hydrochloride using mannosylated poly(propyleneimine) dendrimers

International Nuclear Information System (INIS)

Soni, Namrata; Jain, Keerti; Gupta, Umesh; Jain, N. K.

2015-01-01

The aim of the present investigation was to deliver Gemcitabine Hydrochloride (GmcH), an anticancer bioactive, specifically to lung tumor cells using mannosylated 4.0G poly(propyleneimine) dendrimers (M-PPI). 4.0G poly(propyleneimine) (PPI) dendrimers was synthesized using ethylenediamine as core and conjugated with mannose by ring opening reactions, followed by Schiff’s reaction in the presence of sodium acetate buffer (pH 4.0). Synthesized PPI dendrimers and mannose-conjugated dendrimers were characterized using IR, NMR spectroscopy, and scanning electron microscopy. GmcH was loaded into PPI and M-PPI dendrimers using equilibrium dialysis method to develop the formulations, GmcH-PPI and GmcH-M-PPI, respectively. The developed formulations were evaluated for drug loading, in vitro release kinetics, in vitro stability, hemolytic toxicity, cytotoxicity, pharmacokinetic, and biodistribution studies. The dendrimeric formulation of GmcH showed pH-sensitive release with faster release at acidic pH, i.e., pH 4.0 in comparison with physiological pH 7.4. M-PPI conjugate showed significant reduction in hemolytic toxicity as compared to plain 4.0G PPI dendrimers towards human erythrocytes. In the cytotoxicity studies with A-549 lung adenocarcinoma cell line, the GmcH-M-PPI formulation showed the lowest IC 50 value. Further, the pharmacokinetic and tissue distribution studies of free drug GmcH, GmcH-PPI, and GmcH-M-PPI in albino rats of Sprague–Dawley strain suggested the mean residence time of GmcH-M-PPI conjugate to be significantly higher (24.85 h) than free GmcH and GmcH-PPI. Deposition of drug (396.1 ± 4.7 after 2 h) in lung was found to be significantly higher with GmcH-M-PPI formulation in comparison with Gmch and GmcH-PPI

Controlled delivery of Gemcitabine Hydrochloride using mannosylated poly(propyleneimine) dendrimers

Energy Technology Data Exchange (ETDEWEB)

Soni, Namrata; Jain, Keerti, E-mail: keertijain02@gmail.com; Gupta, Umesh, E-mail: umeshgupta175@gmail.com; Jain, N. K., E-mail: jnarendr@yahoo.co.in [Dr. H. S. Gour Central University, Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences (India)

2015-11-15

The aim of the present investigation was to deliver Gemcitabine Hydrochloride (GmcH), an anticancer bioactive, specifically to lung tumor cells using mannosylated 4.0G poly(propyleneimine) dendrimers (M-PPI). 4.0G poly(propyleneimine) (PPI) dendrimers was synthesized using ethylenediamine as core and conjugated with mannose by ring opening reactions, followed by Schiff’s reaction in the presence of sodium acetate buffer (pH 4.0). Synthesized PPI dendrimers and mannose-conjugated dendrimers were characterized using IR, NMR spectroscopy, and scanning electron microscopy. GmcH was loaded into PPI and M-PPI dendrimers using equilibrium dialysis method to develop the formulations, GmcH-PPI and GmcH-M-PPI, respectively. The developed formulations were evaluated for drug loading, in vitro release kinetics, in vitro stability, hemolytic toxicity, cytotoxicity, pharmacokinetic, and biodistribution studies. The dendrimeric formulation of GmcH showed pH-sensitive release with faster release at acidic pH, i.e., pH 4.0 in comparison with physiological pH 7.4. M-PPI conjugate showed significant reduction in hemolytic toxicity as compared to plain 4.0G PPI dendrimers towards human erythrocytes. In the cytotoxicity studies with A-549 lung adenocarcinoma cell line, the GmcH-M-PPI formulation showed the lowest IC{sub 50} value. Further, the pharmacokinetic and tissue distribution studies of free drug GmcH, GmcH-PPI, and GmcH-M-PPI in albino rats of Sprague–Dawley strain suggested the mean residence time of GmcH-M-PPI conjugate to be significantly higher (24.85 h) than free GmcH and GmcH-PPI. Deposition of drug (396.1 ± 4.7 after 2 h) in lung was found to be significantly higher with GmcH-M-PPI formulation in comparison with Gmch and GmcH-PPI.

What Difference Does Patient and Public Involvement Make and What Are Its Pathways to Impact? Qualitative Study of Patients and Researchers from a Cohort of Randomised Clinical Trials.

Directory of Open Access Journals (Sweden)

Louise Dudley

Full Text Available Patient and public involvement (PPI is advocated in clinical trials yet evidence on how to optimise its impact is limited. We explored researchers' and PPI contributors' accounts of the impact of PPI within trials and factors likely to influence its impact.Semi-structured qualitative interviews with researchers and PPI contributors accessed through a cohort of randomised clinical trials. Analysis of transcripts of audio-recorded interviews was informed by the principles of the constant comparative method, elements of content analysis and informant triangulation.We interviewed 21 chief investigators, 10 trial managers and 17 PPI contributors from 28 trials. The accounts of informants within the same trials were largely in agreement. Over half the informants indicted PPI had made a difference within a trial, through contributions that influenced either an aspect of a trial, or how researchers thought about a trial. According to informants, the opportunity for PPI to make a difference was influenced by two main factors: whether chief investigators had goals and plans for PPI and the quality of the relationship between the research team and the PPI contributors. Early involvement of PPI contributors and including them in responsive (e.g. advisory groups and managerial (e.g. trial management groups roles were more likely to achieve impact compared to late involvement and oversight roles (e.g. trial steering committees.Those seeking to enhance PPI in trials should develop goals for PPI at an early stage that fits the needs of the trial, plan PPI implementation in accordance with these goals, invest in developing good relationships between PPI contributors and researchers, and favour responsive and managerial roles for contributors in preference to oversight-only roles. These features could be used by research funders in judging PPI in trial grant applications and to inform policies to optimise PPI within trials.

The innovative potential of Lactobacillus rhamnosus LR06, Lactobacillus pentosus LPS01, Lactobacillus plantarum LP01, and Lactobacillus delbrueckii Subsp. delbrueckii LDD01 to restore the "gastric barrier effect" in patients chronically treated with PPI: a pilot study.

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Del Piano, Mario; Anderloni, Andrea; Balzarini, Marco; Ballarè, Marco; Carmagnola, Stefania; Montino, Franco; Orsello, Marco; Pagliarulo, Michela; Tari, Roberto; Soattini, Liliana; Sforza, Filomena; Mogna, Luca; Mogna, Giovanni

2012-10-01

Gastroesophageal reflux disease is a very widespread condition. In Europe, it is estimated that about 175 million people suffer from this disease and have to chronically take drugs to increase gastric pH. The proton pump inhibitors (PPIs) such as omeprazole, lansoprazole, and esomeprazole are the most widely used drug typology in this regard. However, the inhibition of normal gastric acid secretion has important side effects, the most important being bacterial overgrowth in the stomach and duodenum with a concentration of >10⁵ viable cells/mL. As a major consequence of this, many harmful or even pathogenic bacteria contained in some foods could survive the gastric transit and colonize either the stomach itself, the duodenum, or the gut, where they could establish acute and even chronic infections with unavoidable consequences for the host's health. In other words, the "gastric barrier effect" is strongly reduced or even disrupted. To date, there are no real strategies to deal with this widespread, although still relatively little known, problem. The aim of this study was to confirm the gastric bacterial overgrowth in long-term PPI consumers and to assess the efficacy of some probiotic bacteria, belonging to both genera Lactobacillus and Bifidobacterium, in the reduction of gastric and duodenal bacterial overgrowth, therefore partially restoring the gastric barrier effect against foodborne pathogenic bacteria. For this purpose, probiotics with a strong demonstrated inhibitory activity on gram-negative bacteria, such as Escherichia coli, were tested in a human intervention trial involving a total of 30 subjects treated with PPIs for either 3 to 12 consecutive months (short-term) or >12 consecutive months (long-term). An additional 10 subjects not taking PPIs were enrolled and used as a control group representing the general population. Four selected probiotics Probiotical SpA (Novara, Italy), namely Lactobacillus rhamnosus LR06 (DSM 21981), Lactobacillus pentosus

Efficacy and safety of lesogaberan in gastro-oesophageal reflux disease: a randomised controlled trial.

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Shaheen, Nicholas J; Denison, Hans; Björck, Karin; Karlsson, Maria; Silberg, Debra G

2013-09-01

Lesogaberan (AZD3355) is a novel γ-aminobutyric acid B-type receptor agonist designed to treat gastro-oesophageal reflux disease (GERD) by inhibiting transient lower oesophageal sphincter relaxations. A randomised, double-blind, placebo-controlled, multi-centre phase IIb study was performed to assess the efficacy and safety of lesogaberan as an add-on to proton pump inhibitor (PPI) therapy in patients with GERD who are partially responsive to PPI therapy (ClinicalTrials.gov reference: NCT01005251). In total, 661 patients were randomised to receive 4 weeks of placebo or 60, 120, 180 or 240 mg of lesogaberan twice daily, in addition to ongoing PPI therapy. Symptoms were measured using the Reflux Symptom Questionnaire electronic Diary. Response to treatment was defined as having an average of ≥ 3 additional days per week of not more than mild GERD symptoms during treatment compared with baseline. In the primary analysis, 20.9%, 25.6%, 23.5% and 26.2% of patients responded to the 60, 120, 180 and 240 mg twice daily lesogaberan doses, respectively, and 17.9% responded to placebo. The response to the 240 mg twice daily dose was statistically significantly greater than the response to placebo using a one-sided test at the predefined significance level of p < 0.1. However, the absolute increases in the proportions of patients who responded to lesogaberan compared with placebo were low. Lesogaberan was generally well tolerated, although six patients receiving lesogaberan developed reversible elevated alanine transaminase levels. In patients with GERD symptoms partially responsive to PPI therapy, lesogaberan was only marginally superior to placebo in achieving an improvement in symptoms.

Design, fabrication, and characterization of polymeric bioMEMS for the detection of feline immunodeficiency virus (FIV)

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Cohen, Brian; Gadre, Anand; Kaloyeros, Alain E.

2007-02-01

This project comprises the development of a novel polymeric BioMEMS device capable of rapidly detecting FIV in a minimally invasive manner. FIV severely inhibits the infected feline from mounting an immune response, and causes susceptibility to other types of diseases. Vaccines against FIV do exist, but have some strong limitations to their effectiveness; so early detection is the best method to combat the spread of the disease. Current testing methods look for antibodies to the FIV protein p24 in feline blood using established Enzyme Linked ImmunoSorbent Assay (ELISA) protocols. The focus of this research is to design and construct a device that can detect antibodies to p24 in a salivary sample by non-intrusive electrochemical means. The device is constructed upon a silicon substrate with gold microelectrodes coated with polypyrrole (PPy), an electrically conducting and biocompatible polymer. In the current phase of the research, the PPy deposition process has been optimized with regards to film thickness, uniformity and conductivity. Microfluidic channels have been fabricated using SU-8, an epoxy based polymer that enables the test sample and other solutions to pass freely through the device. The PPy will be coated with anti-FIV p24 antibodies that can capture FIV p24 antigens present in a salivary sample. Future research will involve the analysis of PPy/antibody interaction and its effect on functionality. The capture of such antigens will interfere with a reduction-oxidation (redox) reaction in a subsequently added ionic solution. This interference will change the characteristic resistance of the solution yielding a qualitative test for the presence of the viral antigens in the sample and hence determining the occurrence of infection.

Inhibition of ethylene production by putrescine alleviates aluminium-induced root inhibition in wheat plants.

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Yu, Yan; Jin, Chongwei; Sun, Chengliang; Wang, Jinghong; Ye, Yiquan; Zhou, Weiwei; Lu, Lingli; Lin, Xianyong

2016-01-08

Inhibition of root elongation is one of the most distinct symptoms of aluminium (Al) toxicity. Although putrescine (Put) has been identified as an important signaling molecule involved in Al tolerance, it is yet unknown how Put mitigates Al-induced root inhibition. Here, the possible mechanism was investigated by using two wheat genotypes differing in Al resistance: Al-tolerant Xi Aimai-1 and Al-sensitive Yangmai-5. Aluminium caused more root inhibition in Yangmai-5 and increased ethylene production at the root apices compared to Xi Aimai-1, whereas the effects were significantly reversed by ethylene biosynthesis inhibitors. The simultaneous exposure of wheat seedlings to Al and ethylene donor, ethephon, or ethylene biosynthesis precursor, 1-aminocyclopropane-1-carboxylic acid (ACC), increased ethylene production and aggravated root inhibition, which was more pronounced in Xi Aimai-1. In contrast, Put treatment decreased ethylene production and alleviated Al-induced root inhibition in both genotypes, and the effects were more conspicuous in Yangmai-5. Furthermore, our results indicated that Al-induced ethylene production was mediated by ACC synthase (ACS) and ACC oxidase, and that Put decreased ethylene production by inhibiting ACS. Altogether, these findings indicate that ethylene is involved in Al-induced root inhibition and this process could be alleviated by Put through inhibiting ACS activity.

Poly(1-(2-carboxyethyl)pyrrole)/polypyrrole composite nanowires for glucose biosensor

International Nuclear Information System (INIS)

Jiang Hairong; Zhang Aifeng; Sun Yanan; Ru Xiaoning; Ge Dongtao; Shi Wei

2012-01-01

A novel glucose biosensor based on poly(1-(2-carboxyethyl)pyrrole) (PPyCOOH)/polypyrrole (PPy) composite nanowires was developed by immobilizing glucose oxidase (GOD) on the nanowires via covalent linkages. The PPyCOOH/PPy composite nanowires were fabricated by a facile two-step electrochemical synthesis route. First, PPy nanowires were synthesized in phosphate buffer solution using organic sulfonic acid, p-toluenesulfonate acid, as soft-template. Then, PPyCOOH/PPy composite nanowires were obtained by polymerizing 1-(2-carboxyethyl)pyrrole onto PPy nanowires via electrochemical method. Scanning electron microscopic, FT-IR spectra, X-ray photoelectron spectroscopy and cyclic voltammograms were used to characterize the structural and electrical behaviors of the composite nanowires. The PPyCOOH/PPy composite nanowires exhibited uniform diameter, high reactive site (-COOH), large specific surface, excellent electroactivity and good adhesion to electrode. The glucose biosensor was constructed by covalently coupling GOD to the composite nanowires. The biosensor response was rapid (5 s), highly sensitive (33.6 μA mM −1 cm −2 ) with a wide linear range (up to 10.0 mM) and low detection limit (0.63 μM); it also exhibited high stability and specificity to glucose. The attractive electrochemical and structural properties of PPyCOOH/PPy composite nanowires suggested potential application for electrocatalysis and biosensor.

Extent, quality and impact of patient and public involvement in antimicrobial drug development research: A systematic review.

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Evans, David; Bird, Emma; Gibson, Andy; Grier, Sally; Chin, Teh Li; Stoddart, Margaret; MacGowan, Alasdair

2018-02-01

Patient and public involvement (PPI) is increasingly recognized as bringing a range of benefits to clinical and health services research. Recent systematic reviews have identified and synthesized many benefits (eg higher recruitment rates) and some costs (eg extra time need). Much of the literature focuses on PPI in long-term conditions rather than more acute health care in which the majority of microbiological research is undertaken. The aim was to identify the extent, quality and impact of PPI in antimicrobial drug development research. Objectives were to identify any relevant reporting of PPI in antimicrobial research; appraise the quality of reporting on PPI using recognized PPI reporting and critical appraisal tools; and extract and synthesize data on the impact of PPI. A systematic review was undertaken with a search strategy based on four word groups (PPI, patients, antimicrobial drug development and outcomes). Eight online databases were searched. English language publication, publication between 1996 and 2016 and studies describing PPI in antimicrobial drug development research. No studies were found through online searching that met the search strategy and inclusion criteria. One relevant protocol paper with a brief mention of PPI was identified through expert recommendation. Commentary papers recommending PPI were identified through website searching and expert opinion. Despite strong policy guidance encouraging PPI at the international and national levels, and anecdotal accounts of PPI taking place, evidence for the extent, quality and impact of PPI in antimicrobial drug development research has not yet appeared in the peer-reviewed literature. © 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.

Externally Controlled Injection of Electrons by a Laser Pulse in a Laser Wakefield Electron Accelerator

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Chen Szu Yuan; Chen Wei Ting; Chien, Ting-Yei; Lee, Chau-Hwang; Lin, Jiunn-Yuan; Wang, Jyhpyng

2005-01-01

Spatially and temporally localized injection of electrons is a key element for development of plasma-wave electron accelerator. Here we report the demonstration of two different schemes for electron injection in a self-modulated laser wakefield accelerator (SM-LWFA) by using a laser pulse. In the first scheme, by implementing a copropagating laser prepulse with proper timing, we are able to control the growth of Raman forward scattering and the production of accelerated electrons. We found that the stimulated Raman backward scattering of the prepulse plays the essential role of injecting hot electrons into the fast plasma wave driven by the pump pulse. In the second scheme, by using a transient density ramp we achieve self-injection of electrons in a SM-LWFA with spatial localization. The transient density ramp is produced by a prepulse propagating transversely to drill a density depression channel via ionization and expansion. The same mechanism of injection with comparable efficiency is also demonstrated wi...

Schlieren, Phase-Contrast, and Spectroscopy Diagnostics for the LBNL HIF Plasma Channel Experiment

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Ponce, D. M.; Niemann, C.; Fessenden, T. J.; Leemans, W.; Vandersloot, K.; Dahlbacka, G.; Yu, S. S.; Sharp, W. M.; Tauschwitz, A.

1999-11-01

The LBNL Plasma Channel experiment has demonstrated stable 42-cm Z-pinch discharge plasma channels with peak currents in excess of 50 kA for a 7 torr nitrogen, 30 kV discharge. These channels offer the possibility of transporting heavy-ion beams for inertial fusion. We postulate that the stability of these channels resides in the existance of a neutral-gas density depresion created by a pre-pulse discharge before the main capacitor bank discharge is created. Here, we present the results and experimental diagnostics setup used for the study of the pre-pulse and main bank channels. Observation of both the plasma and neutral gas dynamics is achieved. Schlieren, Zernike's phase-contrast, and spectroscopic techniques are used. Preliminary Schlieren results show a gas shockwave moving radially at a rate of ≈ 10^6 mm/sec as a result of the fast and localized deposited energy during the evolution of the pre-pulse channel. This data will be used to validate simulation codes (BUCKY and CYCLOPS).

Value of the Gastroesophageal Reflux Disease Questionnaire (GerdQ) in predicting the proton pump inhibitor response in coronary artery disease patients with gastroesophageal reflux-related chest pain.

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He, S; Liu, Y; Chen, Y; Tang, Y; Xu, J; Tang, C

2016-05-01

Chest pain experienced by patients with coronary artery disease can be partly due to gastroesophageal reflux-induced chest pain (GERP). Empirical proton pump inhibitor (PPI) therapy has been recommended as an initial clinical approach for treating GERP. However, PPI use may lead to some health problems. The Gastroesophageal Reflux Disease Questionnaire (GerdQ) may represent a noninvasive and cost-effective approach for avoiding PPI misuse and for identifying the appropriate patients for the PPI trial test. The aim of this pilot study was to prospectively evaluate the association between GerdQ scores and PPI response in patients with coronary artery disease (CAD) and GERP to determine whether the GerdQ predicts the PPI response in patients with CAD and GERP and to further validate the clinical application value of the GerdQ. A total of 154 consecutive patients with potential GERP were recruited to complete a GerdQ with subsequent PPI therapy. Based on the PPI trial result, patients were divided into a PPI-positive response group and a PPI-negative response group. The difference in the GerdQ scores between the two groups was assessed. The receiver operating characteristic (ROC) curve of GerdQ score was drawn according to the PPI response as the gold standard. The ability of GerdQ to predict the PPI response was assessed. A total of 96 patients completed the entire study; 62 patients (64.6%) were assigned to the PPI-positive response group, and 34 patients (35.4%) to the PPI-negative response group. The GerdQ score of the PPI-positive response group (8.11 ± 3.315) was significantly higher than that of the PPI-negative response group (4.41 ± 2.743), and the difference was statistically significant (t = 5.863, P = 0.000). The ROC curve was drawn according to a PPI response assessment result with a score above 2 as the gold standard. The area under curve was 0.806. When the critical value of GerdQ score was 7.5, Youden index was up to 0.514, the diagnostic sensitivity

Behavioral inhibition and obsessive-compulsive disorder.

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Coles, Meredith E; Schofield, Casey A; Pietrefesa, Ashley S

2006-01-01

Behavioral inhibition is frequently cited as a vulnerability factor for development of anxiety. However, few studies have examined the unique relationship between behavioral inhibition and obsessive-compulsive disorder (OCD). Therefore, the current study addressed the relationship between behavioral inhibition and OCD in a number of ways. In a large unselected student sample, frequency of current OC symptoms was significantly correlated with retrospective self-reports of total levels of childhood behavioral inhibition. In addition, frequency of current OC symptoms was also significantly correlated with both social and nonsocial components of behavioral inhibition. Further, there was evidence for a unique relationship between behavioral inhibition and OC symptoms beyond the relationship of behavioral inhibition and social anxiety. In addition, results showed that reports of childhood levels of behavioral inhibition significantly predicted levels of OCD symptoms in adulthood. Finally, preliminary evidence suggested that behavioral inhibition may be more strongly associated with some types of OC symptoms than others, and that overprotective parenting may moderate the impact of behavioral inhibition on OC symptoms. The current findings suggest the utility of additional research examining the role of behavioral inhibition in the etiology of OCD.

Effects of Proton Pump Inhibitor Administration and Intake of a Combination of Yogurt and Galactooligosaccharides on Bone and Mineral Metabolism in Rats

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Satoshi Takasugi

2016-10-01

Full Text Available The aim of this study was to investigate the effects of proton pump inhibitor (PPI, the most potent acid-suppressing drug, administration and intake of a combination of yogurt and galactooligosaccharides (YG on bone and mineral metabolism in adult rats. Twelve-week-old male Wistar rats were divided into three groups: a control group fed the control diet with vehicle administration, a PPI group fed the control diet with PPI administration and a YG + PPI group fed the YG diet with PPI administration. All of the groups received their respective experimental diets and daily subcutaneous injection of the vehicle or PPI for 12 weeks. The PPI group showed significantly lower bone mineral density (BMD of the femur and the lumbar vertebrae and serum fibroblast growth factor 23 (FGF23 and significantly higher phosphorus absorption and serum 1,25-dihydroxyvitamin D (1,25(OH2D than the control group, although PPI did not affect calcium absorption. The PPI + YG group showed significantly higher BMD and serum FGF23 and significantly lower phosphorus absorption and serum 1,25(OH2D than the PPI group. Furthermore, the PPI + YG group showed higher calcium absorption than the control group. These results suggest that although PPI administration did not affect calcium absorption, it adversely affected BMD and influenced phosphorus metabolism in adult rats. Furthermore, the YG diet beneficially affected BMD and attenuated the effects of PPI administration on phosphorus metabolism.

Proton pump inhibitor co-prescription with dual antiplatelet therapy among patients with acute coronary syndrome in Qatar.

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Awaisu, Ahmed; Hamou, Fatima; Mekideche, Lylia; El Muabby, Nisrine; Mahfouz, Ahmed; Mohammed, Shaban; Saad, Ahmad

2016-04-01

There are increasing concerns about clinically significant interactions between proton pump inhibitors (PPIs) and clopidogrel, resulting in adverse cardiovascular outcomes in patients with acute coronary syndromes (ACS). However, published evidence on the prevalence and predictors of PPI use with dual antiplatelet therapy (DAPT) is scarce. This study investigated the prevalence of PPI use among patients with ACS receiving DAPT and possible predictors of co-prescribing the PPIs with the DAPT. Heart Hospital, a specialized tertiary care center in Qatar. A retrospective observational study of a prescription database was conducted. Subjects included 626 patients admitted between January and December 2012 with the diagnosis of ACS who received DAPT and discharged with or without a PPI. Univariate analysis and multivariate binary logistic regression analysis were performed to determine the predictors of PPI-DAPT co-prescription. Prevalence of PPI co-prescribing with DAPT in proportions and percentages and odd ratios for the predictors of PPI-DAPT co-prescribing. A total of 626 patients were analyzed for PPI prevalence, with 200 patients (32 %) being prescribed PPI with DAPT upon discharge. After controlling for confounders, PPI use on admission (aOR 14.5; 95 % CI 7.6-27.6, p < 0.001), nationality (aOR 3.2; 95 % CI 1.1-9.9, p = 0.041), and having a history of diabetes (aOR 0.5; 95 % CI 0.24-0.99, p = 0.046) significantly influenced PPI-DAPT co-prescribing. Users of PPI on admission compared to nonusers were about 15 times more likely to be prescribed PPI with DAPT upon discharge; likewise, having Qatari nationality increased the likelihood of co-prescribing PPI with DAPT upon discharge by three folds. Lastly, patients with a history of diabetes were 50 % less likely to be prescribed PPIs upon discharge compared to those with no history of diabetes. The rate of PPI co-prescribing with DAPT in the population studied was relatively high. The strongest predictor of PPI co

A little more conversation please? Qualitative study of researchers' and patients' interview accounts of training for patient and public involvement in clinical trials.

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Dudley, Louise; Gamble, Carrol; Allam, Alison; Bell, Philip; Buck, Deborah; Goodare, Heather; Hanley, Bec; Preston, Jennifer; Walker, Alison; Williamson, Paula; Young, Bridget

2015-04-27

Training in patient and public involvement (PPI) is recommended, yet little is known about what training is needed. We explored researchers' and PPI contributors' accounts of PPI activity and training to inform the design of PPI training for both parties. We used semi-structured qualitative interviews with researchers (chief investigators and trial managers) and PPI contributors, accessed through a cohort of clinical trials, which had been funded between 2006 and 2010. An analysis of transcripts of audio-recorded interviews drew on the constant comparative method. We interviewed 31 researchers and 17 PPI contributors from 28 trials. Most researchers could see some value in PPI training for researchers, although just under half had received such training themselves, and some had concerns about the purpose and evidence base for PPI training. PPI contributors were evenly split in their perceptions of whether researchers needed training in PPI. Few PPI contributors had themselves received training for their roles. Many informants across all groups felt that training PPI contributors was unnecessary because they already possessed the skills needed. Informants were also concerned that training would professionalise PPI contributors, limiting their ability to provide an authentic patient perspective. However, informants welcomed informal induction 'conversations' to help contributors understand their roles and support them in voicing their opinions. Informants believed that PPI contributors should be confident, motivated, intelligent, focussed on helping others and have relevant experience. Researchers looked for these qualities when selecting contributors, and spoke of how finding 'the right' contributor was more important than accessing 'the right' training. While informants were broadly receptive to PPI training for researchers, they expressed considerable reluctance to training PPI contributors. Providers of training will need to address these reservations. Our

Preparation of Different Substitued Polypyridine Ligands, Ruthenium(II)-Bridged Complexes and Spectoscopıc Studies.

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Obali, Aslihan Yilmaz; Ucan, Halil Ismet

2016-09-01

Novel different substitued polypyridine ligands 4-((4-(1H-imidazo[4,5-f][1,10]phenanthroline-2-yl)phenoxy)methyl)benzaldehyde (BA-PPY), (E)-N-(4-((4-(1H-imidazo[4,5-f][1,10]phenanthroline-2-yl)phenoxy)methyl)benzylidene)-pyrene-4-amine (PR-PPY), (E)-N-(4-((4-(1H-imidazo[4,5-f][1,10] phenanthroline-2-yl)phenoxy)methyl)benzylidene)-1,10-phenanthroline-5amine (FN-PPY), 2-(4-(bromomethyl)phenyl)-1H-imidazo[4,5-f][1,10] phenanthroline (BR-PPY), 2-(4-(azidomethyl)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline (N3-PPY) and triazole containing polypyridine ligand 3,4-bis[(4-(metoxy)-1,2,3-triazole)1-methylphenyl)-1H-imidazo[4,5-f][1,10]phenanthroline)] benzaldehyde (BA-DIPPY) and Ruthenium(II) complexes were synthesized and characterized. Their photopysical properties were investigated. The complexes RuP(PR-PPY), RuB(PR-PPY, RuP(FN-PPY) and RuB(FN-PPY) exhibited a broad absorption bands at 485, 475, 476, and 453 nm, respectively, assignable to the spin-allowed MLCT (dπ-π*) transition. The emission maxima of the pyrene-appended polypyridine ligand PR-PPY was observed at λems = 616 nm and the phenanthroline-appended polypyridine ligand FN-PPY was observed at λems = 668 nm. And the emission maxima of the complexes RuP(PR-PPY), RuB(PR-PPY), RuP(FN-PPY) and RuB(FN-PPY) were observed at λems = 646, 646, 685 and 685 nm, respectively. As seen in fluorescence spectra, the fluorescence intensities of the ligands are higher than their metal complexes. This is because of quenching effect of Ruthenium(II) metal on chromophore groups.

On the development of polypyrrole coatings with self-healing properties for iron corrosion protection

International Nuclear Information System (INIS)

Paliwoda-Porebska, G.; Stratmann, M.; Rohwerder, M.; Potje-Kamloth, K.; Lu, Y.; Pich, A.Z.; Adler, H.-J.

2005-01-01

This paper presents studies on the efficacy and on the limits of polypyrrole (Ppy) doped with either MoO 4 2- or [PMo 12 O 40 ] 3- as self-healing corrosion protecting coatings. The kinetics of the cathodic delamination were studied by means of the Scanning Kelvin Probe (SKP). This method, in combination with cyclic voltammetry, UV-visible spectroscopy (UV-vis) and X-ray photoelectron spectroscopy (XPS), shows a potential driven anion release from the Ppy coating that results in an inhibition of the corrosion process taking place in the defect. Thus, an intelligent release of inhibitor occurs only when the potential at the interface decreases. Inhibitor anions are released only due to an active defect. However, the release mechanism can be easily negatively affected by the presence of small cations and/or by too high pH values at the buried interface. Hence, such a self-healing coating has to be carefully designed in order to ensure an effective performance

Long-term effects of environmentally relevant doses of 2,2',4,4',5,5' hexachlorobiphenyl (PCB153 on neurobehavioural development, health and spontaneous behaviour in maternally exposed mice

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Heegaard Einar

2011-01-01

Full Text Available Abstract Background Polychlorinated biphenyls (PCBs are widespread in the environment, human food and breast milk. Seafood is known to contain nutrients beneficial for the normal development and function of the brain, but also contaminants such as PCBs which are neurotoxic. Exposure to non-coplanar PCBs during brain development can disrupt spontaneous behaviour in mice and lead to hyperactive behaviour. Humans are chronically exposed to the highest relative levels of organochlorines in early childhood during brain development, though usually at doses which do not give clinical symptoms of toxicity. This study aimed to elucidate the developmental and behavioural effects of 2,2',4,4',5,5' hexachlorobiphenyl (PCB153 in mice, mimicking human exposure during gestation and lactation. Methods Environmentally relevant doses of PCB153 were added to the experimental diets. Feed concentrations were approximately 0.5, 6.5, and 1500 μg PCB153/kg feed, representing a realistic and a worst case scenario of frequent consumption of contaminated fish. The study also investigated the effects of maternal nutrition, i.e. a standard rodent diet versus a high inclusion of salmon. Mice pups were examined for physical- and reflex development, sensorimotor function and spontaneous behaviour from five days after birth until weaning. A selection of pups were followed until 16 weeks of age and tested for open field behaviour and the acoustic startle response (ASR with prepulse inhibition (PPI. Blood thyroid hormones and liver enzymes, blood lipids and PCB153 content in fat were examined at 16 weeks. Statistical analyses modelled the three way interactions of diet, PCB exposure and litter size on behaviour, using generalized linear models (GLM and linear mixed effect models (LME. The litter was used as a random variable. Non-parametric tests were used for pair wise comparisons of biochemical analyses. Results Litter size consistently influenced pup development and behaviour

Long-term effects of environmentally relevant doses of 2,2',4,4',5,5' hexachlorobiphenyl (PCB153) on neurobehavioural development, health and spontaneous behaviour in maternally exposed mice.

Science.gov (United States)

Haave, Marte; Bernhard, Annette; Jellestad, Finn K; Heegaard, Einar; Brattelid, Trond; Lundebye, Anne-Katrine

2011-01-13

Polychlorinated biphenyls (PCBs) are widespread in the environment, human food and breast milk. Seafood is known to contain nutrients beneficial for the normal development and function of the brain, but also contaminants such as PCBs which are neurotoxic. Exposure to non-coplanar PCBs during brain development can disrupt spontaneous behaviour in mice and lead to hyperactive behaviour. Humans are chronically exposed to the highest relative levels of organochlorines in early childhood during brain development, though usually at doses which do not give clinical symptoms of toxicity. This study aimed to elucidate the developmental and behavioural effects of 2,2',4,4',5,5' hexachlorobiphenyl (PCB153) in mice, mimicking human exposure during gestation and lactation. Environmentally relevant doses of PCB153 were added to the experimental diets. Feed concentrations were approximately 0.5, 6.5, and 1500 μg PCB153/kg feed, representing a realistic and a worst case scenario of frequent consumption of contaminated fish. The study also investigated the effects of maternal nutrition, i.e. a standard rodent diet versus a high inclusion of salmon. Mice pups were examined for physical- and reflex development, sensorimotor function and spontaneous behaviour from five days after birth until weaning. A selection of pups were followed until 16 weeks of age and tested for open field behaviour and the acoustic startle response (ASR) with prepulse inhibition (PPI). Blood thyroid hormones and liver enzymes, blood lipids and PCB153 content in fat were examined at 16 weeks. Statistical analyses modelled the three way interactions of diet, PCB exposure and litter size on behaviour, using generalized linear models (GLM) and linear mixed effect models (LME). The litter was used as a random variable. Non-parametric tests were used for pair wise comparisons of biochemical analyses. Litter size consistently influenced pup development and behaviour. Few lasting PCB153 related changes were observed

Mechanical, barrier and morphological properties of pea starch and peanut protein isolate blend films.

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Sun, Qingjie; Sun, Cuixia; Xiong, Liu

2013-10-15

Mechanical, barrier and morphological properties of edible films based on blends of Pea starch (PS) and Peanut protein isolate (PPI) plasticized with glycerol (30%, w/w) were investigated. As PPI ratio in PS/PPI blends increased, the thickness of films decreased, the opacity slightly elevated and color intensified. The addition of PPI to the PS film significantly reduced tensile strength from 5.44 MPa to 3.06 MPa, but increased elongation from 28.56% to 98.12% with the incorporation of PPI into PS at 50% level. Film solubility value fell from 22.31% to 9.78% upon the incorporation of PPI ranged from 0 to 50% level. When PPI was added into PS film at 40% level, the WVP and WVTR of the films markedly dropped from 11.18% to 4.19% and 6.16 to 1.95%, respectively. Scanning electron microscopy (SEM) of the surface of films showed that many swollen starch granules were presented in the 100% PS film, while 100% PPI film was observed to have rougher surfaces with presence of pores or cavities. The PS/PPI blend films upon the incorporation of PPI at 20% and 50% level were not homogeneous. However, the smoother film surface was observed in PS/PPI blend films with the addition of PPI at 40% level. SEM image of the cross-sections of the films revealed that the 100% PS film showed a uniform and compact matrix without disruption, and pore formation and 100% PPI film displayed a smooth structure. Rougher and flexible network was shown in blend film with the addition of PPI reaching 40% level. Copyright © 2013. Published by Elsevier Ltd.

Study on the relationship between PI3K/AKT signaling pathway and apoptosis in cartilage tissue of rats with osteoarthritis

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Xiao-Yan Li

2017-05-01

Full Text Available Objective: To study the relationship between PI3K/AKT signaling pathway and apoptosis in cartilage tissue of rats with osteoarthritis (OA. Methods: The clean male Wistar rats were selected as experimental animals and randomly divided into OA model group and control group. The OA model was established by intra-articular injection of papain solution and L-cysteine. Fourth weeks and eighth weeks after model establishment, the expression of PI3K/AKT signaling molecules, inflammatory mediators, apoptosis marker molecules and autophagy marker molecules in articular cartilage were determined. Results: p-PI3K and p-AKT expression in articular cartilage of OA group were significantly lower than those of control group; IL-1β, IL-6, IL-17, IL-18, eIF4E, Bax, Caspase-3, mTOR, Beclin1, Atg5 and Atg7 expression in articular cartilage of OA group were significantly higher than those of control group and negatively correlated with p-PI3K and p-AKT expression while Bcl-2 expression in articular cartilage of OA group was significantly lower than that of control group and positively correlated with p-PI3K and p-AKT expression. Conclusion: The inhibition of PI3K/AKT signaling pathway in cartilage tissue of OA rat model can promote chondrocyte apoptosis and autophagy.

Electrochemical fabrication and electronic behavior of polypyrrole nano-fiber array devices

International Nuclear Information System (INIS)

Liu Ling; Zhao Yaomin; Jia Nengqin; Zhou Qin; Zhao Chongjun; Yan Manming; Jiang Zhiyu

2006-01-01

Electrochemically active Polypyrrole (PPy) nano-fiber array device was fabricated via electrochemical deposition method using aluminum anodic oxide (AAO) membrane as template. After alkaline treatment electrochemically active PPy nano-fiber lost electrochemical activity, and became electrochemically inactive PPy. The electronic properties of PPy nano-fiber array devices were measured by means of a simple method. It was found that for an indium-tin oxide/electrochemically inactive PPy nano-fiber device, the conductivity of nano-fiber increased with the increase of voltage applied on the two terminals of nano-fiber. The electrochemical inactive PPy nano-fiber might be used as a nano-fiber switching diode. Both Au/electrochemically active PPy and Au/electrochemically inactive PPy nano-fiber devices demonstrate rectifying behavior, and might have been used for further application as nano-rectifiers

Electrochemical fabrication and electronic behavior of polypyrrole nano-fiber array devices

Energy Technology Data Exchange (ETDEWEB)

Ling, Liu [Department of Chemistry, and Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai 200433 (China); Yaomin, Zhao [Department of Chemistry, and Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai 200433 (China); Nengqin, Jia [Department of Chemistry, and Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai 200433 (China); Qin, Zhou [Department of Chemistry, and Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai 200433 (China); Chongjun, Zhao [Photon Craft Project, Shanghai Institute of Optics and Fine Mechanics, Chinese Academy of Sciences and Japan Science and Technology Agency, Shanghai 201800 (China); Manming, Yan [Department of Chemistry, and Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai 200433 (China); Zhiyu, Jiang [Department of Chemistry, and Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai 200433 (China)

2006-05-01

Electrochemically active Polypyrrole (PPy) nano-fiber array device was fabricated via electrochemical deposition method using aluminum anodic oxide (AAO) membrane as template. After alkaline treatment electrochemically active PPy nano-fiber lost electrochemical activity, and became electrochemically inactive PPy. The electronic properties of PPy nano-fiber array devices were measured by means of a simple method. It was found that for an indium-tin oxide/electrochemically inactive PPy nano-fiber device, the conductivity of nano-fiber increased with the increase of voltage applied on the two terminals of nano-fiber. The electrochemical inactive PPy nano-fiber might be used as a nano-fiber switching diode. Both Au/electrochemically active PPy and Au/electrochemically inactive PPy nano-fiber devices demonstrate rectifying behavior, and might have been used for further application as nano-rectifiers.

Electrochemical behavior of polypyrrole/chitosan composite coating on Ti metal for biomedical applications.

Science.gov (United States)

Rikhari, Bhavana; Pugal Mani, S; Rajendran, N

2018-06-01

In the present work, the corrosion resistance performance and biocompatibility of polypyrrole/chitosan (PPy/CHI) composite coated Ti was studied. The deposition of composite coating was carried out by electropolymerization method. The deposited PPy/CHI composite coatings were different in morphology, structural, surface roughness and wettability compared PPy coated Ti. The presence of composite coating was confirmed by solid 13 C NMR. The PPy/CHI composite coating showed enhanced microhardness and adhesion strength compared to the PPy coating. The corrosion protection ability of PPy/CHI composite coatings at various applied potentials was analyzed by dynamic electrochemical impedance spectroscopy (DEIS), exhibited higher impedance in all the potentials compared to uncoated and PPy coated Ti. The lower corrosion current density obtained for PPy/CHI-2 composite coating from polarization studies revealed increased corrosion protection ability in SBF solution. The stability of composite coating was confirmed by immersion studies. PPy/CHI-2 composite coating immersed in SBF solution enhances hydroxyapatite (HAp) formation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Ionic liquid assisted mechanochemical preparation and electrochemical performance of graphene nanosheets/polypyrrole composite for supercapacitor

Energy Technology Data Exchange (ETDEWEB)

Lu, X.J.; Zhang, X.G.; Yang, S.D.; Hao, L. [Nanjing Univ. of Aeronautics and Astronautics (China). College of Material Science and Engineering

2010-07-01

Carbons, metal oxides, and conducting polymers are the main materials used to construct supercapacitor electrodes. As a conducting polymer, polypyrrole (PPy) is both environmentally friendly and has high capacitive characteristics. In this study, an ionic liquid (IL) assisted mechanochemical technique was used to prepare a graphene nanosheet (GNS) PPy composite. 1-butyl-3-methylimidazolium tetrachloroferrate (Bmim[FeC1{sub 4}]) was used as a bifunctional IL, as both the dispersant of the GNS and as the oxidant of the PPy. The specific capacitance of the GNS, PPy, and GNS-PPy composites were calculated. Results of the study suggested that the superior performance of the GNS-PPy composite was caused by the synergistic effect between the GNS and PPy. Use of the GNS as a supporting material provided a relatively large area on which to deposit PPy particles, which allowed more PPy to participate in faradaic redox reactions. Electrical conductivity was also improved. 2 refs., 1 fig.

EXCHANGE RATE PASS-THROUGH INTO IMPORT PRICES:EVIDENCE FROM CENTRAL ASIA

Directory of Open Access Journals (Sweden)

Gulnara Moldasheva

2013-01-01

Full Text Available This paper estimates the degree of exchange rate pass-through (ERPT intoimport prices for Central Asiacountries over period 1995q11-2012q11 years.The additional study was done for Kazakhstan to determine the impact ofmoney regulating policy into short-run and long-run ERPT. The study ofERPT was done by employing cointegration analysis across five central Asiacountries: Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan and Uzbekistan.The paper analyzes three opportunities ofthe transmission of the export costinto ERPT using production price indices(PPI of three major trading partnersof Central Asia countries: PPI of Russia, PPI of Turkey and PPI of China.In case with PPI of Russia the resultsshowed, that ERPT is extended beyondof 1 for Kazakhstan and Kyrgyzstan.Incomplete ERPT is indicated forTajikistan and Turkmenistan, and zero ERPT is indicated for Uzbekistan. Incase with PPI of Turkey, the elasticitiesof extent ERPT intoimport prices aremore higher then in case with PPI ofRussia, and elasticities for all CentralAsia countries are negative and significant. In case with PPI of China,incomplete ERPT is indicated for all Central Asia countries, except theKyrgyzstan, which has extended ERPT. In all cases this study showed thesignificance of ERPT, except only two cases for Kazakhstan and Tajikistanwith PPI of China. Also interesting, those elasticities ofERPT with PPI ofChina are lower comparing with othercases. In the special study of moneyregulation policy only for Kazakhstan theshort-run and long-run elasticities ofERPT are incomplete with PPI of Russia and PPI of Turkey, and they areextended with PPI of China.

Use of proton pump inhibitors is associated with increased mortality due to nosocomial pneumonia in bedridden patients receiving tube feeding.

Science.gov (United States)

Hamai, Kosuke; Iwamoto, Hiroshi; Ohshimo, Shinichiro; Wakabayashi, Yu; Ihara, Daisuke; Fujitaka, Kazunori; Hamada, Hironobu; Ono, Koichi; Hattori, Noboru

2018-05-22

To investigate the association between the use of proton pump inhibitors (PPI) and nosocomial pneumonia and gastrointestinal bleeding in bedridden patients receiving tube feeding. A total of 116 bedridden hospitalized patients receiving tube feeding, of which 80 were supported by percutaneous endoscopic gastrostomy and 36 by nasogastric tube, were included in the present study. The patients were divided into two groups: 62 patients treated with PPI (PPI group) and 54 patients without PPI (non-PPI group). Mortality due to nosocomial pneumonia was evaluated using the Kaplan-Meier approach and the log-rank test. A total of 36 patients (31%) died of nosocomial pneumonia during the observation period; the mortality rate due to nosocomial pneumonia was significantly higher in the PPI group than in the non-PPI group (P = 0.0395). Cox proportional hazard analysis showed that the use of PPI and lower levels of serum albumin were independent predictors of 2-year mortality due to nosocomial pneumonia. Gastrointestinal bleeding was observed in four patients in the non-PPI group (7.7%) and in one patient in the PPI group (1.6%); there was no significant difference between the two groups. The use of PPI in bedridden tube-fed patients was independently associated with mortality due to nosocomial pneumonia, and the PPI group had a non-significant lower incidence of gastrointestinal bleeding than the non-PPI group. Geriatr Gerontol Int 2018; ••: ••-••. © 2018 The Authors Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.

Brand name and generic proton pump inhibitor prescriptions in the United States: insights from the national ambulatory medical care survey (2006-2010).

Science.gov (United States)

Gawron, Andrew J; Feinglass, Joseph; Pandolfino, John E; Tan, Bruce K; Bove, Michiel J; Shintani-Smith, Stephanie

2015-01-01

Introduction. Proton pump inhibitors (PPI) are one of the most commonly prescribed medication classes with similar efficacy between brand name and generic PPI formulations. Aims. We determined demographic, clinical, and practice characteristics associated with brand name PPI prescriptions at ambulatory care visits in the United States. Methods. Observational cross sectional analysis using the National Ambulatory Medical Care Survey (NAMCS) of all adult (≥18 yrs of age) ambulatory care visits from 2006 to 2010. PPI prescriptions were identified by using the drug entry code as brand name only or generic available formulations. Descriptive statistics were reported in terms of unweighted patient visits and proportions of encounters with brand name PPI prescriptions. Global chi-square tests were used to compare visits with brand name PPI prescriptions versus generic PPI prescriptions for each measure. Poisson regression was used to determine the incidence rate ratio (IRR) for generic versus brand PPI prescribing. Results. A PPI was prescribed at 269.7 million adult ambulatory visits, based on 9,677 unweighted visits, of which 53% were brand name only prescriptions. In 2006, 76.0% of all PPI prescriptions had a brand name only formulation compared to 31.6% of PPI prescriptions in 2010. Visits by patients aged 25-44 years had the greatest proportion of brand name PPI formulations (57.9%). Academic medical centers and physician-owned practices had the greatest proportion of visits with brand name PPI prescriptions (58.9% and 55.6% of visits with a PPI prescription, resp.). There were no significant differences in terms of median income, patient insurance type, or metropolitan status when comparing the proportion of visits with brand name versus generic PPI prescriptions. Poisson regression results showed that practice ownership type was most strongly associated with the likelihood of receiving a brand name PPI over the entire study period. Compared to HMO visits

Inhibition of polyphenoloxidase by sulfite

International Nuclear Information System (INIS)

Sayavedra-Soto, L.A.; Montgomery, M.W.

1986-01-01

When polyphenoloxidase (PPO) was exposed to sulfite prior to substrate addition, inhibition was irreversible. Trials to regenerate PPO activity, using extensive dialysis, column chromatography, and addition of copper salts were not successful. Increased concentrations of sulfite and pH levels less than 5 enhanced the inhibition of PPO by sulfite. At pH 4, concentrations greater than 0.04 mg/mL completely inhibited 1000 units of PPO activity almost instantaneously. This suggested that the HSO 3 - molecule was the main component in the sulfite system inhibiting PPO. Column chromatography, extensive dialysis, and gel electrophoresis did not demonstrate 35 SO 2 bound to purified pear PPO protein. Formation of extra protein bands of sulfite inhibited purified pear PPO fractions on gel electrophoresis was demonstrated. This and other evidence suggested that the major mode of direct irreversible inhibition of PPO was modification of the protein structure, with retention of its molecular unity

76 FR 4997 - Medicare Program; Inpatient Psychiatric Facilities Prospective Payment System-Update for Rate...

Science.gov (United States)

2011-01-27

... Chemicals cost category, we used a blended PPI composed of the PPI for Industrial Gases, the PPI for Other... using the PPI for Commercial Natural Gas (BLS series code WPU0552). For the proposed FY 2008-based...

Magnetically insulated H- diodes

International Nuclear Information System (INIS)

Fisher, A.; Bystritskii, V.; Garate, E.; Prohaska, R.; Rostoker, N.

1993-01-01

At the Univ. of California, Irvine, the authors have been studying the production of intense H - beams using pulse power techniques for the past 7 years. Previously, current densities of H - ions for various diode designs at UCI have been a few A/cm 2 . Recently, they have developed diodes similar to the coaxial design of the Lebedev Physical Institute, Moscow, USSR, where current densities of up to 200 A/cm 2 were reported using nuclear activation of a carbon target. In experiments at UCI employing the coaxial diode, current densities of up to 35 A/cm 2 from a passive polyethylene cathode loaded with TiH 2 have been measured using a pinhole camera and CR-39 track recording plastic. The authors have also been working on a self-insulating, annular diode which can generate a directed beam of H - ions. In the annular diode experiments a plasma opening switch was used to provide a prepulse and a current path which self-insulated the diode. These experiments were done on the machine APEX, a 1 MV, 50 ns, 7 Ω pulseline with a unipolar negative prepulse of ∼ 100 kV and 400 ns duration. Currently, the authors are modifying the pulseline to include an external LC circuit which can generate a bipolar, 150 kV, 1 μs duration prepulse (similar prepulse characteristic as in the Lebedev Institute experiments cited above)

Inulin significantly improves serum magnesium levels in proton pump inhibitor-induced hypomagnesaemia.

Science.gov (United States)

Hess, M W; de Baaij, J H F; Broekman, M; Bisseling, T M; Haarhuis, B; Tan, A; Te Morsche, R; Hoenderop, J G J; Bindels, R J M; Drenth, J P H

2016-06-01

Proton pump inhibitors (PPI) are among the most widely prescribed drugs to treat gastric acid-related disorders. PPI-induced hypomagnesaemia, a defect in intestinal absorption of Mg(2+) , can be a severe side effect of chronic PPI use. To restore serum Mg(2+) concentrations in PPI-induced hypomagnesaemia patients by dietary supplementation with inulin fibres. Eleven patients with PPI-induced hypomagnesaemia and 10 controls were treated with inulin (20 g/day). Each trial consisted of two cycles of 14-day inulin treatment followed by a washout period of 14 days. Patients continued to use their PPI. Serum Mg(2+) levels served as the primary endpoint. Inulin significantly enhanced serum Mg(2+) levels from 0.60 to 0.68 mmol/L in PPI-induced hypomagnesaemia patients, and from 0.84 to 0.93 mmol/L in controls. As a consequence 24 h urinary Mg(2+) excretion was significantly increased in patients with PPI-induced hypomagnesaemia (0.3-2.2 mmol/day). Symptoms related to hypomagnesaemia, including muscle cramps and paraesthesia, were reduced during intervention with inulin. Inulin increases serum Mg(2+) concentrations under PPI maintenance in patients with PPI-induced hypomagnesaemia. © 2016 John Wiley & Sons Ltd.

Genetics of Adverse Reactions to Haloperidol in a Mouse Diallel: A Drug–Placebo Experiment and Bayesian Causal Analysis

Science.gov (United States)

Crowley, James J.; Kim, Yunjung; Lenarcic, Alan B.; Quackenbush, Corey R.; Barrick, Cordelia J.; Adkins, Daniel E.; Shaw, Ginger S.; Miller, Darla R.; de Villena, Fernando Pardo-Manuel; Sullivan, Patrick F.; Valdar, William

2014-01-01

Haloperidol is an efficacious antipsychotic drug that has serious, unpredictable motor side effects that limit its utility and cause noncompliance in many patients. Using a drug–placebo diallel of the eight founder strains of the Collaborative Cross and their F1 hybrids, we characterized aggregate effects of genetics, sex, parent of origin, and their combinations on haloperidol response. Treating matched pairs of both sexes with drug or placebo, we measured changes in the following: open field activity, inclined screen rigidity, orofacial movements, prepulse inhibition of the acoustic startle response, plasma and brain drug level measurements, and body weight. To understand the genetic architecture of haloperidol response we introduce new statistical methodology linking heritable variation with causal effect of drug treatment. Our new estimators, “difference of models” and “multiple-impute matched pairs”, are motivated by the Neyman–Rubin potential outcomes framework and extend our existing Bayesian hierarchical model for the diallel (Lenarcic et al. 2012). Drug-induced rigidity after chronic treatment was affected by mainly additive genetics and parent-of-origin effects (accounting for 28% and 14.8% of the variance), with NZO/HILtJ and 129S1/SvlmJ contributions tending to increase this side effect. Locomotor activity after acute treatment, by contrast, was more affected by strain-specific inbreeding (12.8%). In addition to drug response phenotypes, we examined diallel effects on behavior before treatment and found not only effects of additive genetics (10.2–53.2%) but also strong effects of epistasis (10.64–25.2%). In particular: prepulse inhibition showed additivity and epistasis in about equal proportions (26.1% and 23.7%); there was evidence of nonreciprocal epistasis in pretreatment activity and rigidity; and we estimated a range of effects on body weight that replicate those found in our previous work. Our results provide the first

Effect of perinatally supplemented flavonoids on brain structure, circulation, cognition, and metabolism in C57BL/6J mice.

Science.gov (United States)

Janssen, Carola I F; Zerbi, Valerio; Mutsaers, Martina P C; Jochems, Mieke; Vos, Claudia A; Vos, Julle O; Berg, Brian M; van Tol, Eric A F; Gross, Gabriele; Jouni, Zeina E; Heerschap, Arend; Kiliaan, Amanda J

2015-10-01

Evidence suggests that flavanol consumption can beneficially affect cognition in adults, but little is known about the effect of flavanol intake early in life. The present study aims to assess the effect of dietary flavanol intake during the gestational and postnatal period on brain structure, cerebral blood flow (CBF), cognition, and brain metabolism in C57BL/6J mice. Female wild-type C57BL/6J mice were randomly assigned to either a flavanol supplemented diet or a control diet at gestational day 0. Male offspring remained on the corresponding diets throughout life and performed cognitive and behavioral tests during puberty and adulthood assessing locomotion and exploration (Phenotyper and open field), sensorimotor integration (Rotarod and prepulse inhibition), and spatial learning and memory (Morris water maze, MWM). Magnetic resonance spectroscopy and imaging at 11.7T measured brain metabolism, CBF, and white and gray matter integrity in adult mice. Biochemical and immunohistochemical analyses evaluated inflammation, synaptic plasticity, neurogenesis, and vascular density. Cognitive and behavioral tests demonstrated increased locomotion in Phenotypers during puberty after flavanol supplementation (p = 0.041) but not in adulthood. Rotarod and prepulse inhibition demonstrated no differences in sensorimotor integration. Flavanols altered spatial learning in the MWM in adulthood (p = 0.039), while spatial memory remained unaffected. Additionally, flavanols increased diffusion coherence in the visual cortex (p = 0.014) and possibly the corpus callosum (p = 0.066) in adulthood. Mean diffusion remained unaffected, a finding that corresponds with our immunohistochemical data showing no effect on neurogenesis, synaptic plasticity, and vascular density. However, flavanols decreased CBF in the cortex (p = 0.001) and thalamus (p = 0.009) in adulthood. Brain metabolite levels and neuroinflammation remained unaffected by flavanols. These data suggest

Function of brain α2B-adrenergic receptor characterized with subtype-selective α2B antagonist and KO mice.

Science.gov (United States)

Luhrs, Lauren; Manlapaz, Cynthia; Kedzie, Karen; Rao, Sandhya; Cabrera-Ghayouri, Sara; Donello, John; Gil, Daniel

2016-12-17

Noradrenergic signaling, through the α 2A and α 2C adrenergic receptors modulates the cognitive and behavioral symptoms of disorders such as schizophrenia, attention deficit hyperactivity disorder (ADHD), and addiction. However, it is unknown whether the α 2B receptor has any significant role in CNS function. The present study elucidates the potential role of the α 2B receptor in CNS function via the discovery and use of the first subtype-selective α 2B antagonist (AGN-209419), and behavioral analyses of α-receptor knockout (KO) mice. Using AGN-209419 as radioligand, α 2B receptor binding sites were identified within the olfactory bulb, cortex, thalamus, cerebellum, and striatum. Based on the observed expression patterns of α 2 subtypes in the brain, we compared α 2B KO, α 2A KO and α 2C KO mice behavioral phenotypes with their respective wild-type lines in anxiety (plus maze), compulsive (marble burying), and sensorimotor (prepulse inhibition) tasks. α 2B KO mice exhibited increased marble burying and α 2C KO mice exhibited an increased startle response to a pulse stimulus, but otherwise intact prepulse inhibition. To further explore compulsive behavior, we evaluated novelty-induced locomotor hyperactivity and found that α 2B KO and α 2C KO mice exhibited increased locomotion in the open field. Interestingly, when challenged with amphetamine, α 2C KO mice increased activity at lower doses relative to either α 2A KO or WT mice. However, α 2B KO mice exhibited stereotypy at doses of amphetamine that were only locomotor stimulatory to all other genotypes. Following co-administration of AGN-209419 with low-dose amphetamine in WT mice, stereotypy was observed, mimicking the α 2B KO phenotype. These findings suggest that the α 2B receptor is involved in CNS behaviors associated with sensorimotor gating and compulsivity, and may be therapeutically relevant for disorders such as schizophrenia, ADHD, post-traumatic stress disorder, addiction, and

The effect of the NMDA channel blocker memantine on salicylate-induced tinnitus in rats.

Science.gov (United States)

Ralli, M; Troiani, D; Podda, M V; Paciello, F; Eramo, S L M; de Corso, E; Salvi, R; Paludetti, G; Fetoni, A R

2014-06-01

Short-term tinnitus develops shortly after the administration of a high dose of salicylate. Since salicylate selectively potentiates N-methyl- D-aspartate (NMDA) currents in spiral ganglion neurons, it may play a vital role in tinnitus by amplifying NMDA-mediated neurotransmission. The aim of this study was to determine whether systemic treatment with a NMDA channel blocker, memantine, could prevent salicylate-induced tinnitus in animals. Additional experiments were performed to evaluate the effect of memantine on the auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) to test for changes in hearing function. Thirty-six rats were divided into 3 groups and treated daily for four consecutive days. One group (n = 12) was injected with salicylate (300 mg/kg/d, IP), the second (n = 12) was treated with memantine (5 mg/kg/d, IP) and the third group (n = 12) was injected with salicylate and memantine. All rats were tested for tinnitus and hearing loss at 2, 24, 48 and 72 h after the first drug administration and 24 h post treatment; tinnituslike behaviour was assessed with gap prepulse inhibition of acoustic startle (GPIAS), and hearing function was measured with DPOAE, ABR and noise burst prepulse inhibition of acoustic startle (NBPIAS). Rats in the salicylate group showed impaired GPIAS indicative of transient tinnitus-like behaviour near 16 kHz that recovered 24 h after the last salicylate treatment. Memantine did not cause a significant change in GPIAS. Combined injection of salicylate and memantine significantly attenuated GPIAS tinnitus-like behaviour at 48 hours after the first injection. None of the treatments induced permanent threshold shifts in the ABR and DPOAE, which recovered completely within one day post treatment. Animals treated with salicylate plus memantine showed results comparable to animals treated with salicylate alone, confirming that there is no effect of memantine on DPOAE which reflects OHC function. The

Science.gov (United States)

RALLI, M.; TROIANI, D.; PODDA, M.V.; PACIELLO, F.; ERAMO, S.L.M.; DE CORSO, E.; SALVI, R.; PALUDETTI, G.; FETONI, A.R.

2014-01-01

SUMMARY Short-term tinnitus develops shortly after the administration of a high dose of salicylate. Since salicylate selectively potentiates N-methyl- D-aspartate (NMDA) currents in spiral ganglion neurons, it may play a vital role in tinnitus by amplifying NMDA-mediated neurotransmission. The aim of this study was to determine whether systemic treatment with a NMDA channel blocker, memantine, could prevent salicylate-induced tinnitus in animals. Additional experiments were performed to evaluate the effect of memantine on the auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) to test for changes in hearing function. Thirty-six rats were divided into 3 groups and treated daily for four consecutive days. One group (n = 12) was injected with salicylate (300 mg/kg/d, IP), the second (n = 12) was treated with memantine (5 mg/kg/d, IP) and the third group (n = 12) was injected with salicylate and memantine. All rats were tested for tinnitus and hearing loss at 2, 24, 48 and 72 h after the first drug administration and 24 h post treatment; tinnituslike behaviour was assessed with gap prepulse inhibition of acoustic startle (GPIAS), and hearing function was measured with DPOAE, ABR and noise burst prepulse inhibition of acoustic startle (NBPIAS). Rats in the salicylate group showed impaired GPIAS indicative of transient tinnitus-like behaviour near 16 kHz that recovered 24 h after the last salicylate treatment. Memantine did not cause a significant change in GPIAS. Combined injection of salicylate and memantine significantly attenuated GPIAS tinnitus-like behaviour at 48 hours after the first injection. None of the treatments induced permanent threshold shifts in the ABR and DPOAE, which recovered completely within one day post treatment. Animals treated with salicylate plus memantine showed results comparable to animals treated with salicylate alone, confirming that there is no effect of memantine on DPOAE which reflects OHC function

Tcf4 Regulates Synaptic Plasticity, DNA Methylation, and Memory Function.

Science.gov (United States)

Kennedy, Andrew J; Rahn, Elizabeth J; Paulukaitis, Brynna S; Savell, Katherine E; Kordasiewicz, Holly B; Wang, Jing; Lewis, John W; Posey, Jessica; Strange, Sarah K; Guzman-Karlsson, Mikael C; Phillips, Scott E; Decker, Kyle; Motley, S Timothy; Swayze, Eric E; Ecker, David J; Michael, Todd P; Day, Jeremy J; Sweatt, J David

2016-09-06

Human haploinsufficiency of the transcription factor Tcf4 leads to a rare autism spectrum disorder called Pitt-Hopkins syndrome (PTHS), which is associated with severe language impairment and development delay. Here, we demonstrate that Tcf4 haploinsufficient mice have deficits in social interaction, ultrasonic vocalization, prepulse inhibition, and spatial and associative learning and memory. Despite learning deficits, Tcf4(+/-) mice have enhanced long-term potentiation in the CA1 area of the hippocampus. In translationally oriented studies, we found that small-molecule HDAC inhibitors normalized hippocampal LTP and memory recall. A comprehensive set of next-generation sequencing experiments of hippocampal mRNA and methylated DNA isolated from Tcf4-deficient and WT mice before or shortly after experiential learning, with or without administration of vorinostat, identified "memory-associated" genes modulated by HDAC inhibition and dysregulated by Tcf4 haploinsufficiency. Finally, we observed that Hdac2 isoform-selective knockdown was sufficient to rescue memory deficits in Tcf4(+/-) mice. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

The effects of a reminder of underwater trauma on behaviour and memory-related mechanisms in the rat dentate gyrus.