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Sample records for nmda blocking effect

  1. The opioid ketobemidone has a NMDA blocking effect

    DEFF Research Database (Denmark)

    Andersen, S; Dickenson, A H; Kohn, M

    1996-01-01

    -fibre strength and their responses quantified. The wind-up of the neurones, due to N-methyl-D-aspartate (NMDA) receptor activation, leading to marked increases in C-fibre responses and an associated post-discharge was also measured. Ketobemidone, applied to the spinal cord, equivalent to an intrathecal injection...... with a Ki value of 26 microM. Therefore, ketobemidone appears to possess both mu opioid agonist as well as NMDA blocking effects....

  2. Effect of NMDA, a Specific Agonist to NMDA Receptor Complex, on Rat Hippocampus.

    Science.gov (United States)

    Motin, V G; Yasnetsov, V V

    2015-10-01

    Removal of Mg2+ ions from perfusion medium provoked epileptiform activity in CA1 field of surviving rat hippocampal slices manifested in generation of extra population spikes. MK-801 (100 μM), a specific non-competitive antagonist to NMDA-receptor complex, prevented this effect. NMDA (20 μM), the specific agonist to this complex, produced no significant effect on the orthodromic population spikes, but when applied at concentrations of 30 or 40 μM, it inhibited them partially (by 21-28%) or almost completely (by 98-99%), correspondingly. Thus, depending on concentration, NMDA can inhibit the synaptic transmission in Schaffer collaterals-hippocampal CA1 pyramidal neurons axis without triggering the epileptiform activity. D-AP5 (50 μM), a competitive antagonist to NMDA-receptor complex, completely prevented the inhibitory effect of NMDA (40 μM). While MK-801 (100 μM) almost completely prevented the inhibitory effect of NMDA, it did not eliminate it when applied after the agonist. Thus, MK-801 can prevent the inhibitory action of NMDA on synaptic transmission in Schaffer collaterals-hippocampal CA1 pyramidal neurons axis via blocking the channel of NMDA-receptor complex, while NMDA exerts its effect only via activation of NMDA receptors.

  3. Contributions of space-clamp errors to apparent time-dependent loss of Mg2+ block induced by NMDA.

    Science.gov (United States)

    Sun, Min-Yu; Chisari, Mariangela; Eisenman, Lawrence N; Zorumski, Charles F; Mennerick, Steven J

    2017-07-01

    N -methyl-d-aspartate receptors (NMDARs) govern synaptic plasticity, development, and neuronal response to insult. Prolonged activation of NMDARs such as during an insult may activate secondary currents or modulate Mg 2+ sensitivity, but the conditions under which these occur are not fully defined. We reexamined the effect of prolonged NMDAR activation in juvenile mouse hippocampal slices. NMDA (10 μM) elicited current with the expected negative-slope conductance in the presence of 1.2 mM Mg 2+ However, several minutes of continued NMDA exposure elicited additional inward current at -70 mV. A higher concentration of NMDA (100 µM) elicited the current more rapidly. The additional current was not dependent on Ca 2+ , network activity, or metabotropic NMDAR function and did not persist on agonist removal. Voltage ramps revealed no alteration of either reversal potential or NMDA-elicited conductance between -30 mV and +50 mV. The result was a more linear NMDA current-voltage relationship. The current linearization was also induced in interneurons and in mature dentate granule neurons but not immature dentate granule cells, dissociated cultured hippocampal neurons, or nucleated patches excised from CA1 pyramidal neurons. Comparative simulations of NMDA application to a CA1 pyramidal neuron and to a cultured neuron revealed that linearization can be explained by space-clamp errors arising from gradual recruitment of distal dendritic NMDARs. We conclude that persistent secondary currents do not strongly contribute to NMDAR responses in juvenile mouse hippocampus and careful discernment is needed to exclude contributions of clamp artifacts to apparent secondary currents. NEW & NOTEWORTHY We report that upon sustained activation of NMDARs in juvenile mouse hippocampal neurons there is apparent loss of Mg 2+ block at negative membrane potentials. However, the phenomenon is explained by loss of dendritic voltage clamp, leading to a linear current-voltage relationship. Our

  4. NMDA receptor activation antagonizes the NMDA antagonist-induced antianxiety effect in the elevated plus-maze test in mice.

    Science.gov (United States)

    Poleszak, Ewa; Serefko, Anna; Szopa, Aleksandra; Wośko, Sylwia; Dudka, Jarosław; Wróbel, Andrzej; Oniszczuk, Tomasz; Wlaź, Piotr

    2013-01-01

    The purpose of this study was to determine how the activation of different regulatory domains of the NMDA complex affects the antianxiety effect of antagonists acting at its distinct binding sites. The anxiolytic-like activity was assessed by the elevated plus-maze test in mice. The anxiolytic activity of CGP 37849 (a competitive NMDA receptor antagonist) and L-701,324 (an antagonist at glycine site) was confirmed, but effects of both were significantly reduced by N-methyl-D-aspartic acid (NMDA) or by D-serine agonists at glutamate and glycine site of the NMDA receptor complex, respectively. The obtained data suggest that stimulation of the glutamate or glycine recognition site of the NMDA receptor complex significantly decreases the antianxiety properties of antagonists of either site.

  5. Neuroprotective effects of daphnetin against NMDA receptor-mediated excitotoxicity.

    Science.gov (United States)

    Yang, Le; Yang, Qi; Zhang, Kun; Li, Yu-Jiao; Wu, Yu-Mei; Liu, Shui-Bing; Zheng, Lian-He; Zhao, Ming-Gao

    2014-09-15

    The accumulation of glutamate can excessively activate the N-methyl-d-aspartate (NMDA) receptors and cause excitotoxicity. Daphnetin (Dap), a coumarin derivative, is a protein kinase inhibitor that exhibits antioxidant and neuroprotective properties. However, little is known about the neuroprotective effects of Dap on glutamate-induced excitotoxicity. We evaluated the neuroprotective activities in the primary cultured cortical neurons against NMDA-induced excitotoxicity. Pretreatment with Dap significantly prevented NMDA-induced neuronal cell loss. Dap significantly inhibited the neuronal apoptosis by regulating balance of Bcl-2 and Bax expression. Furthermore, pretreatment of Dap reversed the up-regulation of NR2B-containing NMDA receptors and inhibited the intracellular Ca2+ overload induced by NMDA exposure. In addition, Dap prevented cerebral ischemic injury in mice induced via a 2 h middle cerebral artery occlusion and a 24 h reperfusion in vivo. The findings suggest that Dap prevents the excitotoxicity through inhibiting the NR2B-containing NMDA receptors and the subsequent calcium overload in cultured cortical neurons.

  6. Comparison of anticonvulsant effect of competitive non-NMDA and noncompetitive NMDA receptor antagonists in adult rats

    Czech Academy of Sciences Publication Activity Database

    Lojková, Denisa; Živanovič, Dragana; Mareš, Pavel

    -, - (2005), s. 160-160 [Conference of the Czech Neuroscience Society /5./, The Annual Meeting of the Network of European Neuroscience Institutes. 19.11.2005-21.11.2005, Prague] R&D Projects: GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : anticonvulsant effect * non-NMDA- receptor antagonist * NMDA receptor antagonist * rats Subject RIV: ED - Physiology

  7. Age dependence of the rapid antidepressant and synaptic effects of acute NMDA receptor blockade

    Directory of Open Access Journals (Sweden)

    Elena eNosyreva

    2014-12-01

    Full Text Available Ketamine is a NMDA receptor antagonist that produces rapid antidepressant responses in individuals with major depressive disorder. The antidepressant action of ketamine has been linked to blocking NMDA receptor activation at rest, which inhibits eukaryotic elongation factor2 kinase leading to desuppression of protein synthesis and synaptic potentiation in the CA1 region of the hippocampus. Here, we investigated ketamine mediated antidepressant response and the resulting synaptic potentiation in juvenile animals. We found that ketamine did not produce an antidepressant response in juvenile animals in the novelty suppressed feeding or the forced swim test. In addition ketamine application failed to trigger synaptic potentiation in hippocampal slices obtained from juvenile animals, unlike its action in slices from older animals (6-9 weeks old. The inability of ketamine to trigger an antidepressant response or subsequent synaptic plasticity processes suggests a developmental component to ketamine mediated antidepressant efficacy. We also show that the NMDAR antagonist AP5 triggers synaptic potentiation in mature hippocampus similar to the action of ketamine, demonstrating that global competitive blockade of NMDA receptors is sufficient to trigger this effect. These findings suggest that global blockade of NMDA receptors in developmentally mature hippocampal synapses are required for the antidepressant efficacy of ketamine.

  8. NMDA antagonists exert distinct effects in experimental organophosphate or carbamate poisoning in mice

    International Nuclear Information System (INIS)

    Dekundy, Andrzej; Kaminski, Rafal M.; Zielinska, Elzbieta; Turski, Waldemar A.

    2007-01-01

    Organophosphate (OP) and carbamate acetylcholinesterase (AChE) inhibitors produce seizures and lethality in mammals. Anticonvulsant and neuroprotective properties of N-methyl-D-aspartate (NMDA) antagonists encourage the investigation of their effects in AChE inhibitor-induced poisonings. In the present study, the effects of dizocilpine (MK-801, 1 mg/kg) or 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 10 mg/kg), alone or combined with muscarinic antagonist atropine (1.8 mg/kg), on convulsant and lethal properties of an OP pesticide dichlorvos or a carbamate drug physostigmine, were studied in mice. Both dichlorvos and physostigmine induced dose-dependent seizure activity and lethality. Atropine did not prevent the occurrence of convulsions but decreased the lethal effects of both dichlorvos and physostigmine. MK-801 or CPP blocked or attenuated, respectively, dichlorvos-induced convulsions. Contrariwise, NMDA antagonists had no effect in physostigmine-induced seizures or lethality produced by dichlorvos or physostigmine. Concurrent pretreatment with atropine and either MK-801 or CPP blocked or alleviated seizures produced by dichlorvos, but not by physostigmine. Both MK-801 and CPP co-administered with atropine enhanced its antilethal effects in both dichlorvos and physostigmine poisoning. In both saline- and AChE inhibitor-treated mice, no interaction of the investigated antidotes with brain cholinesterase was found. The data indicate that both muscarinic ACh and NMDA receptor-mediated mechanisms contribute to the acute toxicity of AChE inhibitors, and NMDA receptors seem critical to OP-induced seizures

  9. Modulation of NMDA receptor function by ketamine and magnesium: Part I

    NARCIS (Netherlands)

    Liu, H. T.; Hollmann, M. W.; Liu, W. H.; Hoenemann, C. W.; Durieux, M. E.

    2001-01-01

    N-methyl-D-aspartate (NMDA) receptors are important components of pain processing. Ketamine and Mg2+ block NMDA receptors and might therefore be useful analgesics, and combinations of Mg2+ and ketamine provide more effective analgesia. We investigated their interactions at NMDA receptors. Xenopus

  10. Neuroprotective Effect of Lutein on NMDA-Induced Retinal Ganglion Cell Injury in Rat Retina.

    Science.gov (United States)

    Zhang, Chanjuan; Wang, Zhen; Zhao, Jiayi; Li, Qin; Huang, Cuiqin; Zhu, Lihong; Lu, Daxiang

    2016-05-01

    Lutein injection is a possible therapeutic approach for retinal diseases, but the molecular mechanism of its neuroprotective effect remains to be elucidated. The aim of this study was to investigate its protective effects in retinal ganglion cells (RGCs) against N-methyl-D-aspartate (NMDA)-induced retinal damage in vivo. Retinal damage was induced by intravitreal NMDA injection in rats. Each animal was given five daily intraperitoneal injections of Lutein or vehicle along with intravitreal NMDA injections. Electroretinograms were recorded. The number of viable RGCs was quantified using the retinal whole-mount method by immunofluorescence. Proteins were measured by Western blot assays. Lutein reduced the retinal damage and improved the response to light, as shown by an animal behavior assay (the black-and-white box method) in rats. Furthermore, Lutein treatment prevented the NMDA-induced reduction in phNR wave amplitude. Lutein increased RGC number after NMDA-induced retina damage. Most importantly, Bax, cytochrome c, p-p38 MAPK, and p-c-Jun were all upregulated in rats injected with NMDA, but these expression patterns were reversed by continuous Lutein uptake. Bcl-2, p-GSK-3β, and p-Akt in the Lutein-treated eyes were increased compared with the NMDA group. Lutein has neuroprotective effects against retinal damage, its protective effects may be partly mediated by its anti-excitability neurotoxicity, through MAPKs and PI3K/Akt signaling, suggesting a potential approach for suppressing retinal neural damage.

  11. Reactive oxygen species and p38 phosphorylation regulate the protective effect of Δ9 –tetrahydrocannabinol in the apoptotic response to NMDA

    Science.gov (United States)

    Chen, Jia; Errico, Stacie L.; Freed, William J.

    2007-01-01

    NMDA causes oxidative stress in neurons, and produces cell death involving elements of both necrosis and apoptosis. To examine the neuroprotective mechanism of Δ9-Tetrahydrocannabinol (THC) in NMDA-induced death of AF5 cells, we measured reactive oxygen species (ROS) formation after exposure to NMDA. ROS generation was increased by NMDA, and NMDA-induced ROS generation was significantly decreased by THC. Western blotting revealed an increase in phosphorylated p38 MAPK after NMDA treatment, which was also blocked by pretreatment with THC. The time course of ROS generation and activation of MAPK signaling pathways were similar. SB203580, a p38 inhibitor, partially blocked glutamate excitotoxicity in AF5 cells. The present data suggest that THC protects against NMDA-induced apoptosis in AF5 cells by blocking ROS generation and inhibiting the activation of p38-MAPK. PMID:16098661

  12. Effects of Block Scheduling

    Directory of Open Access Journals (Sweden)

    William R. Veal

    1999-09-01

    Full Text Available This study examined the effects of a tri-schedule on the academic achievement of students in a high school. The tri-schedule consists of traditional, 4x4 block, and hybrid schedules running at the same time in the same high school. Effectiveness of the schedules was determined from the state mandated test of basic skills in reading, language, and mathematics. Students who were in a particular schedule their freshman year were tested at the beginning of their sophomore year. A statistical ANCOVA test was performed using the schedule types as independent variables and cognitive skill index and GPA as covariates. For reading and language, there was no statistically significant difference in test results. There was a statistical difference mathematics-computation. Block mathematics is an ideal format for obtaining more credits in mathematics, but the block format does little for mathematics achievement and conceptual understanding. The results have content specific implications for schools, administrations, and school boards who are considering block scheduling adoption.

  13. In vivo effects of antibodies from patients with anti-NMDA receptor encephalitis: further evidence of synaptic glutamatergic dysfunction

    OpenAIRE

    Manto, Mario; Dalmau, Josep; Didelot, Adrien; Rogemond, Véronique; Honnorat, Jérôme

    2010-01-01

    Abstract Background A severe encephalitis that associates with auto-antibodies to the NR1 subunit of the NMDA receptor (NMDA-R) was recently reported. Patients' antibodies cause a decrease of the density of NMDA-R and synaptic mediated currents, but the in vivo effects on the extracellular glutamate and glutamatergic transmission are unknown. Methods We investigated the acute metabolic effects of patients' CSF and purified IgG injected in vivo. Injections were performed in CA1 area of Ammon's...

  14. The Neuroprotective Effects of SIRT1 on NMDA-Induced Excitotoxicity

    Directory of Open Access Journals (Sweden)

    Xiaorong Yang

    2017-01-01

    Full Text Available Silent information regulator 1 (SIRT1, an NAD+-dependent deacetylase, is involved in the regulation of gene transcription, energy metabolism, and cellular aging and has become an important therapeutic target across a range of diseases. Recent research has demonstrated that SIRT1 possesses neuroprotective effects; however, it is unknown whether it protects neurons from NMDA-mediated neurotoxicity. In the present study, by activation of SIRT1 using resveratrol (RSV in cultured cortical neurons or by overexpression of SIRT1 in SH-SY5Y cell, we aimed to evaluate the roles of SIRT1 in NMDA-induced excitotoxicity. Our results showed that RSV or overexpression of SIRT1 elicited inhibitory effects on NMDA-induced excitotoxicity including a decrease in cell viability, an increase in lactate dehydrogenase (LDH release, and a decrease in the number of living cells as measured by CCK-8 assay, LDH test, and Calcein-AM and PI double staining. RSV or overexpression of SIRT1 significantly improved SIRT1 deacetylase activity in the excitotoxicity model. Further study suggests that overexpression of SIRT1 partly suppressed an NMDA-induced increase in p53 acetylation. These results indicate that SIRT1 activation by either RSV or overexpression of SIRT1 can exert neuroprotective effects partly by inhibiting p53 acetylation in NMDA-induced neurotoxicity.

  15. Effect of NMDA NR2B antagonist on neuropathic pain in two spinal cord injury models.

    Science.gov (United States)

    Kim, Youngkyung; Cho, Hwi-young; Ahn, Young Ju; Kim, Junesun; Yoon, Young Wook

    2012-05-01

    N-Methyl-d-aspartate (NMDA) receptors are thought to play an important role in the processes of central sensitization and pathogenesis of neuropathic pain, particularly after spinal cord injury (SCI). NMDA antagonists effectively reduce neuropathic pain, but serious side effects prevent their use as therapeutic drugs. NMDA NR2B antagonists have been reported to effectively reduce inflammatory and neuropathic pain. In this study, we investigated the effects of NR2B antagonists on neuropathic pain and the expression of NR2B in the spinal cord in 2 SCI models. SCI was induced at T12 by a New York University impactor (contusion) or by sectioning of the lateral half of the spinal cord (hemisection). Ifenprodil (100, 200, 500, 1000nmol) and Ro25-6981 (20, 50, 100, 200nmol) were intrathecally injected and behavioral tests were conducted. Ifenprodil increased the paw withdrawal threshold in both models but also produced mild motor depression at higher doses. Ro25-6981 increased the mechanical nociceptive threshold in a dose-dependent manner without motor depression. NR2B expression was significantly increased on both sides at the spinal segments of L1-2 and L4-5 in the hemisection model but did not change in the contusion model. Increased expression of NR2B in the hemisection model was reduced by intrathecal ifenprodil. These results suggest that intrathecal NMDA NR2B antagonist increased the mechanical nociceptive threshold after SCI without motor depression. A selective subtype of NMDA receptor, such as NR2B, may be a more selective target for pain control because NMDA receptors play a crucial role in the development and maintenance of chronic pain. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  16. Dual effect of 17β-estradiol on NMDA-induced neuronal death: involvement of metabotropic glutamate receptor 1.

    Science.gov (United States)

    Spampinato, Simona Federica; Merlo, Sara; Molinaro, Gemma; Battaglia, Giuseppe; Bruno, Valeria; Nicoletti, Ferdinando; Sortino, Maria Angela

    2012-12-01

    Pretreatment with 10 nm 17β-estradiol (17βE2) or 100 μm of the metabotropic glutamate 1 receptor (mGlu1R) agonist, dihydroxyphenylglycine (DHPG), protected neurons against N-methyl-d-aspartate (NMDA) toxicity. This effect was sensitive to blockade of both estrogen receptors and mGlu1R by their respective antagonists. In contrast, 17βE2 and/or DHPG, added after a low-concentration NMDA pulse (45 μm), produced an opposite effect, i.e. an exacerbation of NMDA toxicity. Again this effect was prevented by both receptor antagonists. In support of an interaction of estrogen receptors and mGlu1R in mediating a neurotoxic response, exacerbation of NMDA toxicity by 17βE2 disappeared when cultures were treated with DHPG prior to NMDA challenge, and conversely, potentiation of NMDA-induced cell death by DHPG was prevented by pretreatment with 17βE2. Addition of calpain III inhibitor (10 μm), 2 h before NMDA, prevented the increased damage induced by the two agonists, an affect that can be secondary to cleavage of mGlu1R by calpain. Accordingly, NMDA stimulation reduced expression of the full-length (140 kDa) mGluR1, an effect partially reversed by calpain inhibitor. Finally, in the presence of NMDA, the ability of 17βE2 to stimulate phosphorylation of AKT and ERK was impaired. Pretreatment with calpain inhibitor prevented the reduction of phosphorylated ERK but had no significant effect on phosphorylated AKT. Accordingly, the inhibition of ERK signaling by U0126 (1 μm) counteracted the effect of calpain inhibition on 17βE2-induced exacerbation of NMDA toxicity. The present data confirm the dual role of estrogens in neurotoxicity/neuroprotection and highlight the role of the timing of exposure to estrogens.

  17. Differential effect of NMDA and AMPA receptor blockade on protein synthesis in the rat infarct borderzone

    DEFF Research Database (Denmark)

    Christensen, Thomas; Bruhn, T; Frank, L

    1996-01-01

    We investigated whether the known neuroprotective effects of two selective glutamate receptor antagonists, the NMDA antagonist MK-801 and the AMPA antagonist NBQX, are reflected in the regional cerebral protein synthesis rates (CPSR) in rats with middle cerebral artery occlusion (MCAO). Rats...

  18. The effect of the NMDA receptor-dependent signaling pathway on cell morphology and melanosome transfer in melanocytes.

    Science.gov (United States)

    Ni, Jing; Wang, Nan; Gao, Lili; Li, Lili; Zheng, Siwen; Liu, Yuejian; Ozukum, Molu; Nikiforova, Anna; Zhao, Guangming; Song, Zhiqi

    2016-12-01

    The pigmentation of skin and hair in mammals is driven by the intercellular transfer of melanosome from the melanocyte to surrounding keratinocytes However, the detailed molecular mechanism is still a subject of investigation. To investigate the effects of N-methyl-d-aspartate (NMDA) receptor-dependent signaling pathway on melanocyte morphologic change and melanosome transfer between melanocytes and keratinocytes. The expression and the intracellular distribution of NMDA receptor in human melanocyte were analyzed by Western blot and immunofluorescence staining. Melanocytes were treated with 100μM NMDA receptor antagonist MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine maleate] and 100μM NMDA receptor agonist NMDA, after which the morphological change of melanocyte dendrites and filopodias were observed by scanning electron microscope. The β-tubulin distribution and intracellular calcium concentration ([Ca 2+ ] i ) were observed by immunofluorescence staining and flow cytometry under the same treatment respectively. In addition, melanocytes and keratinocytes were co-cultured with or without treatment of MK-801, and the melanosome transfer efficacy were analyzed by flow cytometry. We show that human epidermal melanocytes expresses NMDA receptor 1, one subtype of the ionotropic glutamate receptors (iGluRs). Stimulation with agonist of NMDA receptor increased the number of melanocyte filopodia. In contrast, blockage of NMDA receptor with antagonist decreased the number of melanocyte filopodia and this morphological change was accompanied by the disorganization of β-tubulin microfilaments in the intracellular cytoskeleton. In melanocyte-keratinocyte co-cultures, numerous melanocyte filopodia connect to keratinocyte plasma membranes; agonist of NMDA receptor exhibited an increased number of melanocyte filopodia attachments to keratinocyte, while antagonist of NMDA receptor led to a decreased. Moreover, antagonist of NMDA receptor decreased

  19. [Neuroprotective effect of erigeron breviscapus (vant) hand-mazz on NMDA-induced retinal neuron injury in the rats].

    Science.gov (United States)

    Shi, Jingming; Jiag, Youqin; Liu, Xuyang

    2004-07-01

    To investigate if Erigeron Breviscapus (vant) Hand-Mazz (EBHM) has a neuroprotective effect against NMDA-induced neuron death in retinal ganglion cell layer (RGCL). Sixty healthy SD rats were randomly divided into four groups. 6 animals were in normal control group (group A). The others were divided as group B (EBHM group), group C (normal saline+NMDA group), group D (EBHM+NMDA group). Each group has 18 rats. 10 nmol NMDA was chosen for intravitreal injection to cause partial damage of the neurons in RGCL in the right eyes of Groups C and D. Same volume PBS was intravitreal injected in the left eyes as self-control. Groups B and D were pre-treated intraperitoneally with 6% EBHM solution at a dose of 15 mg x 100 g(-1) x d(-1) seven days before and after NMDA treatment. Group C were administrated intraperitoneally with 0.9% normal saline at the same time of EBHM injection. Rats were sacrificed in 4, 7, 14 days after NMDA treatment. Flat preparation of whole retinas were stained with 0.5% cresyl violet and neuron counting in RGCL from both eyes. Each subgroup has 6 rats. There was no significant difference between the right eye and the left eye of neuron counting from RGCL in normal control group (group A) (P=0.200). There was no significant difference between normal control group and EBHM group either in the right eyes or in the left eye in 4 days, 7 days and 14 days respectively after intravitreal injection of 10 nmol NMDA in group C and group D. (P=0.636, P=0.193). Neuron counting from RGCL of group C and group D were significant decreased in the NMDA-treated eyes in 4 days, 7 days and 14 days after intravitreal injection (P 0.05). Neuron counting was significantly higher in the EBHM+NMDA group than normal saline+NMDA group at 14 days after intraviteal injection (P=0.044). However,it is obvious that the difference was still significant between normal control group and EBHM+NMDA group (P < 0.05). EBHM has no effect on neuron counting of RGCL when administered alone

  20. Involvement of direct inhibition of NMDA receptors in the effects of sigma-receptor ligands on glutamate neurotoxicity in vitro.

    Science.gov (United States)

    Nishikawa, H; Hashino, A; Kume, T; Katsuki, H; Kaneko, S; Akaike, A

    2000-09-15

    This study was performed to examine the roles of the N-methyl-D-aspartate (NMDA) receptor/phencyclidine (PCP) channel complex in the protective effects of sigma-receptor ligands against glutamate neurotoxicity in cultured cortical neurons derived from fetal rats. A 1-h exposure of cultures to glutamate caused a marked loss of viability, as determined by Trypan blue exclusion. This acute neurotoxicity of glutamate was prevented by NMDA receptor antagonists. Expression of sigma(1) receptor mRNA in cortical cultures was confirmed by reverse transcription polymerase chain reaction (RT-PCR). sigma Receptor ligands with affinity for NMDA receptor channels including the PCP site, such as (+)-N-allylnormetazocine ((+)-SKF10,047), haloperidol, and R(-)-N-(3-phenyl-1-propyl)-1-phenyl-2-aminopropane ((-)-PPAP), prevented glutamate neurotoxicity in a concentration-dependent manner. In contrast, other sigma-receptor ligands without affinity for NMDA receptors, such as carbetapentane and R(+)-3-(3-hydroxyphenyl)-N-propylpiperidine ((+)-3-PPP), did not show neuroprotective effects. Putative endogenous sigma receptor ligands such as pregnenolone, progesterone, and dehydroepiandrosterone did not affect glutamate neurotoxicity. The protective effects of (+)-SKF10,047, haloperidol, and (-)-PPAP were not affected by the sigma(1) receptor antagonist rimcazole. These results suggested that a direct interaction with NMDA receptors but not with sigma receptors plays a crucial role in the neuroprotective effects of sigma receptor ligands with affinity for NMDA receptors.

  1. Dual Allosteric Effect in Glycine/NMDA Receptor Antagonism: A Comparative QSAR Approach

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    Vipin B. Gupta

    2010-10-01

    Full Text Available A comparative Hantzsch type QSAR study was conducted using multiple regression analysis on various sets of quinoxalines, quinoxalin-4-ones, quinazoline-2-carboxylates, 4-hydroxyquinolin-2(1H-ones, 2-carboxytetrahydroquinolines, phenyl-hydroxy-quinolones, nitroquinolones and 4-substituted-3-phenylquinolin-2(1H-ones as selective glycine/NMDA site antagonists. Ten statistically validated equations were developed, which indicated the importance of CMR, Verloop’s sterimol L1 and ClogP parameters in contributing towards biological activity. Interestingly, normal and inverse parabolic relationships were found with CMR in different series, indicating a dual allosteric binding mode in glycine/NMDA antagonism. Equations reveal an optimum CMR of 10 ± 10% is required for good potency of antagonists. Other equations indicate the presence of anionic functionality at 4-position of quinoline/quinolone ring system is not absolutely required for effective binding. The observations are laterally validated and in accordance with previous studies.

  2. Stereoselective effects of AMOA on non-NMDA receptors expressed in Xenopus oocytes

    DEFF Research Database (Denmark)

    Wahl, P; Nielsen, B; Krogsgaard-Larsen, P

    1992-01-01

    Pharmacological characterization of the action of the novel non-N-methyl-D-aspartate (non-NMDA) antagonist AMOA (2-amino-3-[3-(carboxymethoxy)-5-methylisoxazol-4-yl]propionate) on glutamate receptors was investigated in Xenopus oocytes injected with mouse brain mRNA. AMOA (150 microM) produced...... antagonistic/agonistic property of AMOA may explain its unusual properties with regard to antagonism of non-NMDA receptor-mediated events previously described....... a nearly parallel shift to the right of the dose-response curve for kainate-induced currents. AMOA was found to have two different effects on AMPA receptors: 1) currents elicited by low concentrations of AMPA (6 microM) were inhibited by AMOA with an IC50 value of 160 +/- 19 microM and 2) currents elicited...

  3. Amphetamine and antidepressant drug effects on GABA- and NMDA-related seizures.

    Science.gov (United States)

    Borowski, T B; Kirkby, R D; Kokkinidis, L

    1993-01-01

    Research has shown a synergistic relationship between amphetamine sensitization and limbic system kindling. To explore the role of GABA and NMDA receptor activity in modulating the positive effects of amphetamine on epileptogenesis, alterations in GABA- and NMDA-related convulsions were examined after acute and chronic amphetamine administration. A single injection of d-amphetamine (7.5 mg/kg) significantly decreased latencies to generalized motor seizures induced 12 h later by the noncompetitive GABAA receptor antagonist picrotoxin (10 mg/kg). The increased sensitivity to clonus was specific to acute amphetamine treatment and was not evident following withdrawal from chronic drug exposure. Seizures induced by NMDLA (1,000 mg/kg), on the other hand, were not modified by acute amphetamine injection; however, the latency to clonus was reduced substantially after NMDLA injection to mice chronically preexposed to amphetamine. The short- and long-term amphetamine effects on GABA- and NMDA-associated convulsive activity were not paralleled by similar drug treatment schedules involving acute (20 mg/kg) and chronic administration of desipramine, zimelidine, and buproprion. These results suggest that amphetamine may be acting on inhibitory and excitatory amino acid systems independently of its monoaminergic properties. The implications of these findings were discussed in relation to amphetamine sensitization of mesolimbic functioning.

  4. In vivo effects of antibodies from patients with anti-NMDA receptor encephalitis: further evidence of synaptic glutamatergic dysfunction

    Directory of Open Access Journals (Sweden)

    Manto Mario

    2010-11-01

    Full Text Available Abstract Background A severe encephalitis that associates with auto-antibodies to the NR1 subunit of the NMDA receptor (NMDA-R was recently reported. Patients' antibodies cause a decrease of the density of NMDA-R and synaptic mediated currents, but the in vivo effects on the extracellular glutamate and glutamatergic transmission are unknown. Methods We investigated the acute metabolic effects of patients' CSF and purified IgG injected in vivo. Injections were performed in CA1 area of Ammon's horn and in premotor cortex in rats. Results Patient's CSF increased the concentrations of glutamate in the extracellular space. The increase was dose-dependent and was dramatic with purified IgG. Patients' CSF impaired both the NMDA- and the AMPA-mediated synaptic regulation of glutamate, and did not affect the glial transport of glutamate. Blockade of GABA-A receptors was associated with a marked elevation of extra-cellular levels of glutamate following a pretreatment with patients' CSF. Conclusion These results support a direct role of NMDA-R antibodies upon altering glutamatergic transmission. Furthermore, we provide additional evidence in vivo that NMDA-R antibodies deregulate the glutamatergic pathways and that the encephalitis associated with these antibodies is an auto-immune synaptic disorder.

  5. The effect of infectious brain edema on NMDA receptor binding in rat's brain

    International Nuclear Information System (INIS)

    Cheng Guansheng; Chen Jianfang; Chen Xiang

    1997-01-01

    PURPOSE: The effect of the infectious brain edema (IBE) induced by Bordetella Pertussis (BP) on the specific binding of 3 H MK-801 in rat's brain in vivo was determined. METHODS: BP was injected via left internal carotid artery in rat model of infectious brain edema. Male SD rats were divided into three groups: 1) Group control (NS, n = 11); 2) Group IBF (BP, n = 12); 3) Group pretreatment of MK-801 + PB (MK-801, n = 4). Normal saline or BP 0.2 ml/kg was injected into left internal carotid artery in NS and BP group respectively. MK-801 0.5 mg/kg per day was injected i.p. two days before injection of BP in group MK-801. Rats were killed by decapitation at 24 hours after injection of BP. The specific binding of N-methyl-D-aspartate (NMDA) receptor were measured with 3 H-MK-801 in the neuronal membrane of cerebral cortex. The Scatchard plots were performed. RESULTS: The B max values were 0.623 +- 0.082 and 0.606 +- 0.087 pmol/mg protein in group NS and BP respectively (t = 0.48, P>0.05). The Kd values were 43.1 +- 4.2 and 30.5 +- 3.0 nmol/L in group NS and BP respectively (t = 7.8, P<0.05). The specific binding of NMDA receptor was decreased by pretreatment of MK-801. CONCLUSIONS: The total number of NMDA receptor had not changed, whereas its affinity increased significantly in the model of brain edema induced by pertussis bacilli in rat. The increase of affinity of NMDA receptor can be blockaded by MK-801 pretreatment in vivo

  6. BQ-869, a novel NMDA receptor antagonist, protects against excitotoxicity and attenuates cerebral ischemic injury in stroke.

    Science.gov (United States)

    Yu, Guo; Wu, Fei; Wang, Er-Song

    2015-01-01

    Stroke is one of the three diseases that cause human death in current world, and it is the common, frequently occurring disease in the middle-old ages. NMDA receptors mediate glutamate-induced cell death when intensely or chronically activated, which is an important cause of neuronal cell death after acute injuries. Here, we demonstrated that BQ-869, a potent NMDA receptor antagonist, blocked NMDA receptor in concentration-dependent and dose-dependent manner, attenuated NMDA-induced Ca(2+) influx, inhabited NMDAR-mEPSC in hippocampal pyramidal neurons, improved athletic ability of rats with MACO, decreased infarction size in focal cerebral ischemia rats and reduced stroke mortality. Taken together, our data demonstrate the neuroprotective effect of BQ-869 might be through inhibiting NMDA-mediated excitotoxicity. These findings indicate that BQ-869 is the most potent antagonist of NMDA receptors, and provide new insights with potential therapeutic applications for the treatment of stroke.

  7. Block of NMDA receptor channels by endogenous neurosteroids: implications for the agonist induced conformational states of the channel vestibule

    Czech Academy of Sciences Publication Activity Database

    Vyklický, Vojtěch; Krausová, Barbora; Černý, Jiří; Balík, Aleš; Zápotocký, Martin; Novotný, M.; Lichnerová, Katarina; Smejkalová, Tereza; Kaniaková, Martina; Kořínek, Miloslav; Petrovič, Miloš; Kačer, P.; Horák, Martin; Chodounská, Hana; Vyklický ml., Ladislav

    2015-01-01

    Roč. 5, Jun 18 (2015), s. 10935 ISSN 2045-2322 R&D Projects: GA ČR(CZ) GPP303/11/P391; GA ČR(CZ) GAP303/12/1464; GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GA14-02219S; GA TA ČR(CZ) TE01020028; GA MŠk(CZ) ED1.1.00/02.0109; GA MŠk(CZ) EE2.3.30.0025 Institutional support: RVO:67985823 ; RVO:61388963 Keywords : NMDA R * ligand-gated * neurotransmitter receptor Subject RIV: ED - Physiology Impact factor: 5.228, year: 2015

  8. Acute 5-HT7 receptor activation increases NMDA-evoked currents and differentially alters NMDA receptor subunit phosphorylation and trafficking in hippocampal neurons.

    Science.gov (United States)

    Vasefi, Maryam S; Yang, Kai; Li, Jerry; Kruk, Jeff S; Heikkila, John J; Jackson, Michael F; MacDonald, John F; Beazely, Michael A

    2013-05-14

    N-methyl-D-aspartate (NMDA) receptors are regulated by several G protein-coupled receptors (GPCRs) as well as receptor tyrosine kinases. Serotonin (5-HT) type 7 receptors are expressed throughout the brain including the thalamus and hippocampus. Long-term (2-24 h) activation of 5-HT7 receptors promotes the expression of neuroprotective growth factor receptors, including the platelet-derived growth factor (PDGF) β receptors which can protect neurons against NMDA-induced neurotoxicity. In contrast to long-term activation of 5-HT7 receptors, acute (5 min) treatment of isolated hippocampal neurons with the 5-HT7 receptor agonist 5-carboxamidotryptamine (5-CT) enhances NMDA-evoked peak currents and this increase in peak currents is blocked by the 5-HT7 receptor antagonist, SB 269970. In hippocampal slices, acute 5-HT7 receptor activation increases NR1 NMDA receptor subunit phosphorylation and differentially alters the phosphorylation state of the NR2B and NR2A subunits. NMDA receptor subunit cell surface expression is also differentially altered by 5-HT7 receptor agonists: NR2B cell surface expression is decreased whereas NR1 and NR2A surface expression are not significantly altered. In contrast to the negative regulatory effects of long-term activation of 5-HT7 receptors on NMDA receptor signaling, acute activation of 5-HT7 receptors promotes NMDA receptor activity. These findings highlight the potential for temporally differential regulation of NMDA receptors by the 5-HT7 receptor.

  9. Non-NMDA receptor antagonist-induced drinking in rat

    Science.gov (United States)

    Xu, Z.; Johnson, A. K.

    1998-01-01

    Glutamate has been implicated in the central control of mechanisms that maintain body fluid homeostasis. The present studies demonstrate that intracerebroventricular (i.c.v.) injections of the non-N-methyl-d-aspartate (NMDA) receptor antagonists 6, 7-dinitroquinoxaline-2,3-dione (DNQX) and 6-cyano-7-nitroquinoxaline-2,3 dione (CNQX) induce drinking in rats. The dipsogenic effect of i.c.v. DNQX was antagonized by the non-NMDA receptor agonist alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). The water intake induced by DNQX was also blocked by pretreatment with a NMDA receptor antagonist, MK-801, but not by angiotensin type 1 (AT1) or acetylcholine muscarinic receptor antagonists (losartan and atropine). The results indicate that non-NMDA receptors may exert a tonic inhibitory effect within brain circuits that control dipsogenic activity and that functional integrity of NMDA receptors may be required for the non-NMDA receptor antagonists to induce water intake. Copyright 1998 Published by Elsevier Science B.V.

  10. Effects of ibuprofen on cognition and NMDA receptor subunit expression across aging.

    Science.gov (United States)

    Márquez Loza, Alejandra; Elias, Valerie; Wong, Carmen P; Ho, Emily; Bermudez, Michelle; Magnusson, Kathy R

    2017-03-06

    Age-related declines in long- and short-term memory show relationships to decreases in N-methyl-d-aspartate (NMDA) receptor expression, which may involve inflammation. This study was designed to determine effects of an anti-inflammatory drug, ibuprofen, on cognitive function and NMDA receptor expression across aging. Male C57BL/6 mice (ages 5, 14, 20, and 26months) were fed ibuprofen (375ppm) in NIH31 diet or diet alone for 6weeks prior to testing. Behavioral testing using the Morris water maze showed that older mice performed significantly worse than younger in spatial long-term memory, reversal, and short-term memory tasks. Ibuprofen enhanced overall performance in the short-term memory task, but this appeared to be more related to improved executive function than memory. Ibuprofen induced significant decreases over all ages in the mRNA densities for GluN2B subunit, all GluN1 splice variants, and GluN1-1 splice forms in the frontal cortex and in protein expression of GluN2A, GluN2B and GluN1 C2' cassettes in the hippocampus. GluN1-3 splice form mRNA and C2' cassette protein were significantly increased across ages in frontal lobes of ibuprofen-treated mice. Ibuprofen did not alter expression of pro-inflammatory cytokines IL-1β and TNFα, but did reduce the area of reactive astrocyte immunostaining in frontal cortex of aged mice. Enhancement in executive function showed a relationship to increased GluN1-3 mRNA and decreased gliosis. These findings suggest that inflammation may play a role in executive function declines in aged animals, but other effects of ibuprofen on NMDA receptors appeared to be unrelated to aging or inflammation. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Agmatine enhances the antidepressant-like effect of lithium in mouse forced swimming test through NMDA pathway.

    Science.gov (United States)

    Mohseni, Gholmreza; Ostadhadi, Sattar; Imran-Khan, Muhammad; Norouzi-Javidan, Abbas; Zolfaghari, Samira; Haddadi, Nazgol-Sadat; Dehpour, Ahmad-Reza

    2017-04-01

    Depression is one the world leading global burdens leading to various comorbidities. Lithium as a mainstay in the treatment of depression is still considered gold standard treatment. Similar to lithium another agent agmatine has also central protective role against depression. Since, both agmatine and lithium modulate various effects through interaction with NMDA receptor, therefore, in current study we aimed to investigate the synergistic antidepressant-like effect of agmatine with lithium in mouse force swimming test. Also to know whether if such effect is due to interaction with NMDA receptor. In our present study we found that when potent dose of lithium (30mg/kg) was administered, it significantly decreased the immobility time. Also, when subeffective dose of agmatine (0.01mg/kg) was coadministered with subeffective dose of lithium (3mg/kg), it potentiated the antidepressant-like effect of subeffective dose of lithium. For the involvement of NMDA receptor in such effect, we administered NMDA receptor antagonist MK-801 (0.05mg/kg) with a combination of subeffective dose of lithium (3mg/kg) and agmatine (0.001mg/kg). A significant antidepressant-like effect was observed. Furthermore, when subeffective dose (50 and 75mg/kg) of NMDA was given it inhibited the synergistic effect of agmatine (0.01mg/kg) with lithium (3mg/kg). Hence, our finding demonstrate that agmatine have synergistic effect with lithium which is mediated by NMDA receptor pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. 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

  13. Effects of Memantine, an NMDA Antagonist, on Metabolic Syndromes in Female NMRI Mice

    Directory of Open Access Journals (Sweden)

    Naser Osanloo

    2015-10-01

    Results: The intraperitoneal administration of memantine increased plasma corticosterone, water intake, fecal weight and eating latency, but had no effect on food intake or weight. The dose and site-dependent intra-accumbens administration of memantine either exacerbated the effects of stress on plasma corticosterone levels and water and food intake, or else had no effect on these parameters. Furthermore, the administration of memantine had no effect on animal’s weight and inhibited the effects of stress on fecal weight and eating latency. Discussion: The inhibition of glutamate NMDA receptors in the nucleus accumbens can inhibit and/or exacerbate the dose and site-dependent effects of chronic stress, with gender playing a significant role in producing this effect.

  14. Effect of NMDA Receptor Antagonist on Local Cerebral Glucose Metabolic Rate in Focal Cerebral Ischemia

    International Nuclear Information System (INIS)

    Kim, Sang Eun; Hong, Seung Bong; Yoon, Byung Woo

    1995-01-01

    There has recently been increasing interest in the use of NMDA receptor antagonists as potential neuroprotective agents for the treatment of ischemic stroke. To evaluate the neuroprotective effect of the selective non-competitive NMDA receptor antagonist MK-801 in focal cerebral ischemia, local cerebral glucose utilization (1CGU) was examined in 15 neuroanatomically discrete regions of the conscious rat brain using the 2-deoxy-D[14C]glucose quantitative autoradiographic technique 24 hr after left middle cerebral artery occlusion (MCAO). Animals received MK-801 (5 mg/kg i.v.) or saline vehicle before (20-30 min) or after (30 min) MCAO. Both pretreatment and posttreatment of MK-801 increased occluded/non-occluded 1CGU ratio in 7 and 5 of the 15 regions measured, respectively(most notably in cortical structures). Following MK-801 pretreatment, there was evidence of widespread increases in 1CCPU not only in the non-occluded hemisphere (12 of the 15 areas studied) but also in the occluded hemisphere (13 of the 15 areas studied), while MK-801 posttreatment did not significantly increase 1CGU both in the normal and occluded hemispheres. These data indicate that MK-801 has a neuroprotective effect in focal cerebral ischemia and demonstrate that MK-801 provides widespread alterations of glucose utilization in conscious animals.

  15. Distinct pharmacological and functional properties of NMDA receptors in mouse cortical astrocytes

    Science.gov (United States)

    Palygin, Oleg; Lalo, Ulyana; Pankratov, Yuriy

    2011-01-01

    BACKGROUND AND PURPOSE Astrocytes of the mouse neocortex express functional NMDA receptors, which are not blocked by Mg2+ ions. However, the pharmacological profile of glial NMDA receptors and their subunit composition is far from complete. EXPERIMENTAL APPROACH We tested the sensitivity of NMDA receptor-mediated currents to the novel GluN2C/D subunit-selective antagonist UBP141 in mouse cortical astrocytes and neurons. We also examined the effect of memantine, an antagonist that has substantially different affinities for GluN2A/B and GluN2C/d-containing receptors in physiological concentrations of extracellular Mg2+. KEY RESULTS UBP141 had a strong inhibitory action on NMDA receptor-mediated transmembrane currents in the cortical layer II/III astrocytes with an IC50 of 2.29 µM and a modest inhibitory action on NMDA-responses in the pyramidal neurons with IC50 of 19.8 µM. Astroglial and neuronal NMDA receptors exhibited different sensitivities to memantine with IC50 values of 2.19 and 10.8 µM, respectively. Consistent with pharmacological differences between astroglial and neuronal NMDA receptors, NMDA receptors in astrocytes showed lower Ca2+ permeability than neuronal receptors with PCa/PNa ratio of 3.4. CONCLUSIONS AND IMPLICATIONS The biophysical and pharmacological properties of the astrocytic NMDA receptors strongly suggest that they have a tri-heteromeric structure composed of GluN1, GluN2C/D and GluN3 subunits. The substantial difference between astroglial and neuronal NMDA receptors in their sensitivity to UBP141 and memantine may enable selective modulation of astrocytic signalling that could be very helpful for elucidating the mechanisms of neuron-glia communications. Our results may also provide the basis for the development of novel therapeutic agents specifically targeting glial signalling. PMID:21449975

  16. BDNF prevents NMDA-induced toxicity in models of Huntington's disease: the effects are genotype specific and adenosine A2A receptor is involved.

    Science.gov (United States)

    Martire, Alberto; Pepponi, Rita; Domenici, Maria Rosaria; Ferrante, Antonella; Chiodi, Valentina; Popoli, Patrizia

    2013-04-01

    NMDA receptor-mediated excitotoxicity is thought to play a pivotal role in the pathogenesis of Huntington's disease (HD). The neurotrophin brain-derived neurotrophic factor (BDNF), which is also highly involved in HD and whose effects are modulated by adenosine A2 ARs, influences the activity and expression of striatal NMDA receptors. In electrophysiology experiments, we investigated the role of BDNF toward NMDA-induced effects in HD models, and the possible involvement of A2ARs. In corticostriatal slices from wild-type mice and age-matched symptomatic R6/2 mice (a model of HD), NMDA application (75 μM) induced a transient or a permanent (i.e., toxic) reduction of field potential amplitude, respectively. BDNF (10 ng/mL) potentiated NMDA effects in wild-type, while it protected from NMDA toxicity in R6/2 mice. Both effects of BDNF were prevented by A2 AR blockade. The protective effect of BDNF against NMDA-induced toxicity was reproduced in a cellular model of HD. These findings may have very important implications for the neuroprotective potential of BDNF and A2 AR ligands in HD. © 2013 International Society for Neurochemistry.

  17. Involvement of NMDA receptors in the beneficial effects of pioglitazone on scopolamine-induced memory impairment in mice.

    Science.gov (United States)

    Almasi-Nasrabadi, Mina; Javadi-Paydar, Mehrak; Mahdavian, Shirin; Babaei, Rosa; Sharifian, Maedeh; Norouzi, Abbas; Dehpour, Ahmad Reza

    2012-05-16

    Pioglitazone, a peroxisome proliferator activated receptor γ (PPARγ) agonist, is widely used in clinical medicine as a treatment for type 2 diabetes and is recently proved to have beneficial effects on improving cognition in early stages of Alzheimer's disease (AD). Moreover, it has been shown that pioglitazone reduces N-methyl-D-aspartate (NMDA, a glutamate agonist) mediated calcium currents and transients. Since enhanced calcium transients are present in AD models, we tested the hypothesis whether pioglitazone manifests its acquisition memory enhancement role through glutamatergic pathway. Memory performance was evaluated in a two-trial recognition Y-maze test and passive avoidance in mice. Pioglitazone (20 or 40 mg/kg, p.o.) was administered 2h before each trial, NMDA (75 mg/kg i.p.), 15 min before pioglitazone, and scopolamine, an M1 (muscarinic) receptor antagonist (0.3 or 1.0 mg/kg i.p.) and MK-801 (dizocilpine) (0.01, 0.03 or 0.1 mg/kg, i.p.), the highly selective, non-competitive NMDA antagonist--30 min beforehand. (1) We induced the memory impairment by scopolamine or MK-801 before trials. (2) Pioglitazone did not improve the memory impairment induced by MK-801. (3) Pioglitazone significantly improved the memory impairment induced by scopolamine. (4) Subeffective dose of MK-801 nullified the beneficial effects of pioglitazone in scopolamine induced memory impaired mice. (5) NMDA promoted the effects of subeffective dose of pioglitazone on memory impaired by scopolamine. In conclusion, the present study suggests that glutamatergic pathway is involved in the pioglitazone induced memory performance. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. In vivo [(123)I]CNS-1261 binding to D-serine-activated and MK801-blocked NMDA receptors: A storage phosphor imaging study in rats

    NARCIS (Netherlands)

    Knol, Remco J. J.; de Bruin, Kora; van Eck-Smit, Berthe L. F.; Pimlott, Sally; Wyper, David J.; Booij, Jan

    2009-01-01

    Disturbances of activity of the glutamatergic neurotransmitter system in the brain are present in many neuropsychiatric disorders. The N-methyl-D-aspartate (NMDA) receptor is the most abundant receptor of the glutamatergic system. In the neurodegenerative events of Alzheimer's disease, excessive

  19. Effect of the selective NMDA NR2B antagonist, ifenprodil, on acute tolerance to ethanol-induced motor impairment in adolescent and adult rats.

    Science.gov (United States)

    Ramirez, Ruby Liane; Varlinskaya, Elena I; Spear, Linda P

    2011-06-01

    Adolescent rats have been observed to be less sensitive than adults to a number of acute ethanol effects, including ethanol-induced motor impairment. These adolescent insensitivities may be related in part to the more rapid emergence of within session (acute) tolerance in adolescents than adults. Adolescent-related alterations in neural systems that serve as ethanol target sites, including changes in NMDA receptor subunit expression, may influence the responsiveness of adolescents to acute ethanol effects. This study explored the role of NMDA NR2B receptors in the development of acute tolerance to ethanol-induced motor impairment in male adolescent [postnatal day (P)28-30] and adult (P68-70) Sprague-Dawley rats. Motor-impairing effects of ethanol on the stationary inclined plane and blood ethanol concentrations (BECs) were examined following challenge at each age with a functionally equivalent ethanol dose (adolescents: 2.25 g/kg; adults: 1.5 g/kg). Data were collected at two postinjection intervals (10 or 60 minutes) to compare rate of recovery from ethanol intoxication with BEC declines using the Radlow approach (Radlow, 1994) and changes in motor impairment/BEC ratios over time for assessing acute tolerance. Both vehicle-treated adolescent and adult animals showed similar acute tolerance development to the motor-impairing effects of ethanol at these functionally equivalent doses on the stationary inclined plane, as indexed by an increasing time-dependent dissociation between BECs and ethanol-induced motor impairment, with motor impairment declining faster than BECs, as well as by significant declines in motor impairment/BEC ratios over time. Acute tolerance development was reliably blocked by administration of the NR2B antagonist, ifenprodil, (5.0 mg/kg), in adult rats, whereas adolescents were affected by a higher dose (10.0 mg/kg). These data support the suggestion that alterations in NMDA receptor systems occurring during adolescence may contribute to

  20. The undesirable effects of neuromuscular blocking drugs

    DEFF Research Database (Denmark)

    Claudius, C; Garvey, L H; Viby-Mogensen, J

    2009-01-01

    Neuromuscular blocking drugs are designed to bind to the nicotinic receptor at the neuromuscular junction. However, they also interact with other acetylcholine receptors in the body. Binding to these receptors causes adverse effects that vary with the specificity for the cholinergic receptor...... in question. Moreover, all neuromuscular blocking drugs may cause hypersensitivity reactions. Often the symptoms are mild and self-limiting but massive histamine release can cause systematic reactions with circulatory and respiratory symptoms and signs. At the end of anaesthesia, no residual effect...... of a neuromuscular blocking drug should be present. However, the huge variability in response to neuromuscular blocking drugs makes it impossible to predict which patient will suffer postoperative residual curarization. This article discusses the undesirable effects of the currently available neuromuscular blocking...

  1. The effect of 1800MHz radio-frequency radiation on NMDA receptor subunit NR1 expression and peroxidation in the rat brain in healthy and inflammatory states.

    Science.gov (United States)

    Bodera, Paweł; Makarova, Katerina; Zawada, Katarzyna; Antkowiak, Bożena; Paluch, Małgorzata; Sobiczewska, Elżbieta; Sirav, Bahriye; Siwicki, Andrzej K; Stankiewicz, Wanda

    2017-08-01

    The aim of this study was to evaluate the effect of repeated exposure (5 times for 15min) of 1800MHz radio-frequency radiation (RFR) on N-methyl-d-aspartate receptor subunit NR1 (NMDA-NR1) expression in the brains of rats in a persistent inflammatory state. We also measured the effect of RFR combined with tramadol (TRAM) to determine the potential antioxidant capacity of this agent. The effects of the Global System for Mobile Communication (GSM) modulated 1800MHz RFR exposure on the expression and activity of glutamate receptor channels with antioxidative activity in brain tissue was measured using oxygen radical absorbance capacity (ORAC) and electron spin resonance (ESR) detection of the hydroxyl radical generated by the Fenton reaction. NMDA-NR1 was measured in the cerebral tissue of rats with inflammation (complete Freund's adjuvent) and those injected with tramadol after RFR exposure (RFR, RFR/TRAM) and in non-exposed (baseline, TRAM) rats. No differences between the baseline group and the exposed group (RFR) were observed. NMDA-NR1 expression decreased after CFA injection and RFR exposure, and an elevated expression of NMDA-NR1 was observed in healthy control rats of both groups: TRAM/RFR and RFR. ORAC assessment revealed a robust effect of RFR, however the other experiments revealed equivocal effects. Further studies examining the combination of ORAC with NMDA are warranted to elucidate more clearly the effect of RFR on the brain. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Investigating the Interactive Effects of Sex Steroid Hormones and Brain-Derived Neurotrophic Factor during Adolescence on Hippocampal NMDA Receptor Expression

    Directory of Open Access Journals (Sweden)

    Cushla R. McCarthny

    2018-01-01

    Full Text Available Sex steroid hormones have neuroprotective properties which may be mediated by brain-derived neurotrophic factor (BDNF. This study sought to determine the interactive effects of preadolescent hormone manipulation and BDNF heterozygosity (+/− on hippocampal NMDA-R expression. Wild-type and BDNF+/− mice were gonadectomised, and females received either 17β-estradiol or progesterone treatment, while males received either testosterone or dihydrotestosterone (DHT treatment. Dorsal (DHP and ventral hippocampus (VHP were dissected, and protein expression of GluN1, GluN2A, GluN2B, and PSD-95 was assessed by Western blot analysis. Significant genotype × OVX interactions were found for GluN1 and GluN2 expression within the DHP of female mice, suggesting modulation of select NMDA-R levels by female sex hormones is mediated by BDNF. Furthermore, within the DHP BDNF+/− mice show a hypersensitive response to hormone treatment on GluN2 expression which may result from upstream alterations in TrkB phosphorylation. In contrast to the DHP, the VHP showed no effects of hormone manipulation but significant effects of genotype on NMDA-R expression. Castration had no effect on NMDA-R expression; however, androgen treatment had selective effects on GluN2B. These data show case distinct, interactive roles for sex steroid hormones and BDNF in the regulation of NMDA-R expression that are dependent on dorsal versus ventral hippocampal region.

  3. Dorsal hippocampal NMDA receptors mediate the interactive effects of arachidonylcyclopropylamide and MDMA/ecstasy on memory retrieval in rats.

    Science.gov (United States)

    Ghaderi, Marzieh; Rezayof, Ameneh; Vousooghi, Nasim; Zarrindast, Mohammad-Reza

    2016-04-03

    A combination of cannabis and ecstasy may change the cognitive functions more than either drug alone. The present study was designed to investigate the possible involvement of dorsal hippocampal NMDA receptors in the interactive effects of arachidonylcyclopropylamide (ACPA) and ecstasy/MDMA on memory retrieval. Adult male Wistar rats were cannulated into the CA1 regions of the dorsal hippocampus (intra-CA1) and memory retrieval was examined using the step-through type of passive avoidance task. Intra-CA1 microinjection of a selective CB1 receptor agonist, ACPA (0.5-4ng/rat) immediately before the testing phase (pre-test), but not after the training phase (post-training), impaired memory retrieval. In addition, pre-test intra-CA1 microinjection of MDMA (0.5-1μg/rat) dose-dependently decreased step-through latency, indicating an amnesic effect of the drug by itself. Interestingly, pre-test microinjection of a higher dose of MDMA into the CA1 regions significantly improved ACPA-induced memory impairment. Moreover, pre-test intra-CA1 microinjection of a selective NMDA receptor antagonist, D-AP5 (1 and 2μg/rat) inhibited the reversal effect of MDMA on the impairment of memory retrieval induced by ACPA. Pre-test intra-CA1 microinjection of the same doses of D-AP5 had no effect on memory retrieval alone. These findings suggest that ACPA or MDMA consumption can induce memory retrieval impairment, while their co-administration improves this amnesic effect through interacting with hippocampal glutamatergic-NMDA receptor mechanism. Thus, it seems that the tendency to abuse cannabis with ecstasy may be for avoiding cognitive dysfunction. Copyright © 2015. Published by Elsevier Inc.

  4. Signaling Cascades Regulating NMDA Receptor Sensitivity to Ethanol

    OpenAIRE

    RON, DORIT

    2004-01-01

    One of the major targets for ethanol (alcohol) in the brain is the N-methyl-d-aspartate (NMDA) receptor, a glutamate-gated ion channel. Intriguingly, the effects of ethanol on the NMDA receptor are not homogeneous throughout the brain. This review focuses on recent studies revealing molecular mechanisms that mediate the actions of ethanol on the NMDA receptor in different brain regions via changes in NMDA receptor phosphorylation and compartmentalization. Specifically, the role of the scaffol...

  5. Uncoupling the D1-N-methyl-D-aspartate (NMDA) receptor complex promotes NMDA-dependent long-term potentiation and working memory.

    Science.gov (United States)

    Nai, Qiang; Li, Shupeng; Wang, Szu-Han; Liu, Jing; Lee, Frank J S; Frankland, Paul W; Liu, Fang

    2010-02-01

    Although dopamine D1 receptors are involved in working memory, how D1 receptors contribute to this process remains unclear. Numerous studies have shown that D1 receptors have extensive functional interaction with N-methyl-D-aspartate (NMDA) receptor. Our group previously demonstrated that D1 receptors were able to regulate NMDA receptor functions through direct protein-protein interactions involving the carboxyl terminals of D1 receptors and NMDA receptor NR1a and NR2A subunits respectively. In this study, we explored the effects of the D1-NR1 interaction on NMDA receptor-dependent long-term potentiation (LTP) and working memory by using the TAT-conjugated interfering peptide (TAT-D1-t2). Miniature excitatory postsynaptic currents are recorded in rat hippocampal primary cultures. Coimmunoprecipitation and calcium/calmodulin-dependent protein kinase II (CaMKII) activity are measured in hippocampal slices and hippocampal neurons under the specified experimental conditions, respectively. Working memory was assessed using a delayed match-to-place protocol in the Morris Water Maze following administration of the TAT-D1-t2 peptide. Electrophysiology experiments showed that activation of D1 receptor upregulates NMDA receptor-mediated LTP in a CaMKII-dependent manner. Furthermore, D1 receptor agonist stimulation promotes the NR1-CaMKII coupling and enhances the CaMKII activity; and the D1 receptor-mediated effects can be blocked by the application of the TAT-D1-t2 peptide. Interestingly, animals injected with TAT-D1-t2 peptide exhibited significantly impaired working memory. Our study showed a critical role of NMDA-D1 direct protein-protein interaction in NMDA receptor-mediated LTP and working memory and implicated the involvement of CaMKII in this process. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  6. Actions of Bupivacaine, a Widely Used Local Anesthetic, on NMDA Receptor Responses

    Science.gov (United States)

    Paganelli, Meaghan A.

    2015-01-01

    NMDA receptors mediate excitatory neurotransmission in brain and spinal cord and play a pivotal role in the neurological disease state of chronic pain, which is caused by central sensitization. Bupivacaine is the indicated local anesthetic in caudal, epidural, and spinal anesthesia and is widely used clinically to manage acute and chronic pain. In addition to blocking Na+ channels, bupivacaine affects the activity of many other channels, including NMDA receptors. Importantly, bupivacaine inhibits NMDA receptor-mediated synaptic transmission in the dorsal horn of the spinal cord, an area critically involved in central sensitization. We used recombinant NMDA receptors expressed in HEK293 cells and found that increasing concentrations of bupivacaine decreased channel open probability in GluN2 subunit- and pH-independent manner by increasing the mean duration of closures and decreasing the mean duration of openings. Using kinetic modeling of one-channel currents, we attributed the observed current decrease to two main mechanisms: a voltage-dependent “foot-in-the-door” pore block and an allosteric gating effect. Further, the inhibition was state-independent because it occurred to the same degree whether the drug was applied before or after glutamate stimulation and was mediated by extracellular and intracellular inhibitory sites, via hydrophilic and hydrophobic pathways. These results predict that clinical doses of bupivacaine would decrease the peak and accelerate the decay of synaptic NMDA receptor currents during normal synaptic transmission. These quantitative predictions inform possible applications of bupivacaine as preventative and therapeutic approaches in chronic pain. PMID:25589775

  7. The dual effect of CA1 NMDA receptor modulation on ACPA-induced amnesia in step-down passive avoidance learning task.

    Science.gov (United States)

    Nasehi, Mohammad; Amin-Yavari, Samaneh; Ebrahimi-Ghiri, Mohaddeseh; Torabi-Nami, Mohammad; Zarrindast, Mohammad-Reza

    2015-04-01

    It is well documented that cannabinoids play an important role in certain hippocampal memory processes in rodents. On the other hand, N-Methyl-d-aspartate receptors (NMDARs) mediate the synaptic plasticity related to learning and memory processes which take place in the hippocampus. Such insights prompted us to investigate the influence of dorsal hippocampal (CA1) NMDA receptor agents on amnesia induced by cannabinoid CB1 receptor agonist, arachidonylcyclopropylamide (ACPA) in male mice. One-trial step-down passive avoidance and hole-board apparatuses were used to examine the memory retrieval and exploratory behaviors, respectively. Based on our findings, pre-training intraperitoneal (i.p.) administration of ACPA (0.01mg/kg) decreased memory acquisition. Moreover, pre-training intra-CA1 infusion of NMDA (0.001, 0.0125, 0.025 and 0.2µg/mouse), d-AP7 (0.5 and 1µg/mouse) or AM251 (50ng/mouse) impaired the memory acquisition. Meanwhile, NMDA-treated animals at the doses of 0.0005, 0.05 and 0.1µg/mouse acquired memory formation. In addition, intra-CA1 microinjection of NMDA (0.0005) plus different doses of ACPA potentiated the ACPA response, while NMDA (0.1) plus the lower or the higher dose of ACPA potentiated or restored the ACPA response, respectively. Further investigation revealed that a subthreshold dose of d-AP7 could potentiate the memory acquisition impairment induced by ACPA. Moreover, the subthreshold dose of AM251 did not alter the ACPA response, while the effective dose of the drug restored the memory acquisition impairment induced by ACPA. According to these results, we concluded that activation of the NMDA receptors in the CA1 mediates a dual effect on ACPA-induced amnesia in step-down passive avoidance learning task. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  8. Novel dimeric bis(7)-tacrine proton-dependently inhibits NMDA-activated currents

    International Nuclear Information System (INIS)

    Luo, Jialie; Li, Wenming; Liu, Yuwei; Zhang, Wei; Fu, Hongjun; Lee, Nelson T.K.; Yu, Hua; Pang, Yuanping; Huang, Pingbo; Xia, Jun; Li, Zhi-Wang; Li, Chaoying; Han, Yifan

    2007-01-01

    Bis(7)-tacrine has been shown to prevent glutamate-induced neuronal apoptosis by blocking NMDA receptors. However, the characteristics of the inhibition have not been fully elucidated. In this study, we further characterize the features of bis(7)-tacrine inhibition of NMDA-activated current in cultured rat hippocampal neurons. The results show that with the increase of extracellular pH, the inhibitory effect decreases dramatically. At pH 8.0, the concentration-response curve of bis(7)-tacrine is shifted rightwards with the IC 50 value increased from 0.19 ± 0.03 μM to 0.41 ± 0.04 μM. In addition, bis(7)-tacrine shifts the proton inhibition curve rightwards. Furthermore, the inhibitory effect of bis(7)-tacrine is not altered by the presence of the NMDA receptor proton sensor shield spermidine. These results indicate that bis(7)-tacrine inhibits NMDA-activated current in a pH-dependent manner by sensitizing NMDA receptors to proton inhibition, rendering it potentially beneficial therapeutic effects under acidic conditions associated with stroke and ischemia

  9. [Sacral block: indications and effectiveness].

    Science.gov (United States)

    Grob, D; Dvorak, J

    1998-02-25

    It has been shown that during injection of 17 to 20 ml local anesthetics combined with a corticosteroid via the hiatus canalis sacralis that the solution is distributed up to the level of the thoraco-lumbar junction. The indication for therapeutical peridural injection are radicular symptoms as a result of disc herniation, foraminal stenosis as well as neurogenic claudicatio. Contraindications are anticoagulation, local infection as well as suspicion of systemic inflammatory disease of the peripheral nervous system. With proper technique and adequate desinfection, complications and side effects are very rare.

  10. Role of NMDA receptor GluN2D subunit in the antidepressant effects of enantiomers of ketamine.

    Science.gov (United States)

    Ide, Soichiro; Ikekubo, Yuiko; Mishina, Masayoshi; Hashimoto, Kenji; Ikeda, Kazutaka

    2017-11-01

    We investigated the rapid and sustained antidepressant effects of enantiomers of ketamine in N-methyl-d-aspartate (NMDA) receptor GluN2D subunit knockout (GluN2D-KO) mice. Intraperitoneal administration of ketamine or its enantiomers 10 min before the tail-suspension test exerted significant antidepressant effects on restraint stress-induced depression in both wildtype and GluN2D-KO mice. The antidepressant effects of (RS)-ketamine and (S)-ketamine were sustained 96 h after the injection in both wildtype and GluN2D-KO mice, but such sustained antidepressant effects of (R)-ketamine were only observed in wildtype mice. These data suggest that the GluN2D subunit is critical for the sustained antidepressant effects of (R)-ketamine. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  11. Role of NMDA receptor GluN2D subunit in the antidepressant effects of enantiomers of ketamine

    Directory of Open Access Journals (Sweden)

    Soichiro Ide

    2017-11-01

    Full Text Available We investigated the rapid and sustained antidepressant effects of enantiomers of ketamine in N-methyl-d-aspartate (NMDA receptor GluN2D subunit knockout (GluN2D-KO mice. Intraperitoneal administration of ketamine or its enantiomers 10 min before the tail-suspension test exerted significant antidepressant effects on restraint stress-induced depression in both wildtype and GluN2D-KO mice. The antidepressant effects of (RS-ketamine and (S-ketamine were sustained 96 h after the injection in both wildtype and GluN2D-KO mice, but such sustained antidepressant effects of (R-ketamine were only observed in wildtype mice. These data suggest that the GluN2D subunit is critical for the sustained antidepressant effects of (R-ketamine.

  12. Effects of 4X4 Block Scheduling

    Directory of Open Access Journals (Sweden)

    R. Brian Cobb

    1999-02-01

    Full Text Available The effects of a 4 X 4 block scheduling program in a middle school on a variety of student measures were investigated. These measures included standardized achievement tests in mathematics, reading, and writing, cumulative and semester grades in middle school and high school, attendance rates, and enrollment rates in advanced high school courses (in mathematics only. The block scheduling program had been in effect for four years allowing analyses of current middle and high school students who had experienced a minimum of one and one-half years of block scheduling while in middle school. The primary research design was a post-test only, matched pairs design. Students were matched on school characteristics, gender, ethnicity, grade level, and 5th grade standardized reading scores. Results were relatively consistent with the extant literature and generally positive.

  13. Nurr1 protein is required for N-methyl-D-aspartic acid (NMDA) receptor-mediated neuronal survival.

    Science.gov (United States)

    Barneda-Zahonero, Bruna; Servitja, Joan-Marc; Badiola, Nahuai; Miñano-Molina, Alfredo J; Fadó, Rut; Saura, Carlos A; Rodríguez-Alvarez, José

    2012-03-30

    NMDA receptor (NMDAR) stimulation promotes neuronal survival during brain development. Cerebellar granule cells (CGCs) need NMDAR stimulation to survive and develop. These neurons differentiate and mature during its migration from the external granular layer to the internal granular layer, and lack of excitatory inputs triggers their apoptotic death. It is possible to mimic this process in vitro by culturing CGCs in low KCl concentrations (5 mm) in the presence or absence of NMDA. Using this experimental approach, we have obtained whole genome expression profiles after 3 and 8 h of NMDA addition to identify genes involved in NMDA-mediated survival of CGCs. One of the identified genes was Nurr1, a member of the orphan nuclear receptor subfamily Nr4a. Our results report a direct regulation of Nurr1 by CREB after NMDAR stimulation. ChIP assay confirmed CREB binding to Nurr1 promoter, whereas CREB shRNA blocked NMDA-mediated increase in Nurr1 expression. Moreover, we show that Nurr1 is important for NMDAR survival effect. We show that Nurr1 binds to Bdnf promoter IV and that silencing Nurr1 by shRNA leads to a decrease in brain-derived neurotrophic factor (BDNF) protein levels and a reduction of NMDA neuroprotective effect. Also, we report that Nurr1 and BDNF show a similar expression pattern during postnatal cerebellar development. Thus, we conclude that Nurr1 is a downstream target of CREB and that it is responsible for the NMDA-mediated increase in BDNF, which is necessary for the NMDA-mediated prosurvival effect on neurons.

  14. Effects of a NR2B Selective NMDA Glutamate Antagonist, CP-101,606, on Dyskinesia and Parkinsonism

    Science.gov (United States)

    Nutt, John G.; Gunzler, Steven A; Kirchhoff, Trish; Hogarth, Penelope; Weaver, Jerry L.; Krams, Michael; Jamerson, Brenda; Menniti, Frank S.; Landen, Jaren W.

    2011-01-01

    Glutamate antagonists decrease dyskinesia and augment the antiparkinsonian effects of levodopa in animal models of Parkinson’s disease (PD). In a randomized, double-blind, placebo-controlled clinical trial we investigated the acute effects of placebo and two doses of a NR2B subunit selective NMDA glutamate antagonist, CP-101,606, on the response to two-hour levodopa infusions in 12 PD subjects with motor fluctuations and dyskinesia. Both doses of CP-101,606 reduced the maximum severity of levodopa-induced dyskinesia approximately 30% but neither dose improved parkinsonism. CP-101,606 was associated with a dose-related dissociation and amnesia. These results support the hypothesis that glutamate antagonists may be useful antidyskinetic agents. However, future studies will have to determine if the benefits of dyskinesia suppression can be achieved without adverse cognitive effects. PMID:18759356

  15. Involvement of NMDA receptors in soman-induced neuropathology

    Energy Technology Data Exchange (ETDEWEB)

    De Groot, D.M.; Bierman, E.P.; Van Huygevoort, A.H.; Bruijnzeel, P.L.

    1993-05-13

    Our current working hypothesis with regard to soman-induced neuropathology is that accumulated ACh, resulting from soman-inhibited ACHE potentiates glutamate-induced neuronal degeneration, most likely by lowering the threshold for glutamate excitation at the NMDA-receptor sites. The activation of the NMDA-ionic channels may lead to massive Ca2+ fluxes into the postsynaptic cell, causing cell degeneration. In this concept the NMDA receptor plays a crucial role. In the present study, the involvement of NMDA receptors in soman-induced convulsions is tested by injecting NMDA receptor antagonists MK801, AP5 and TCP, whether or not in combination with atropine and/or diazepam, either directly into the hippocampal CA1 area or in the lateral ventricle very near to CA1. This area is predominantly affected by soman and contains high concentrations of NMDA receptors. Also the effect of injection with a non-NMDA receptor antagonist is tested.

  16. Endogenous acetylcholine rescues NMDA-induced long-lasting hippocampal cell damage via stimulation of muscarinic M(1) receptors: elucidation using organic hippocampal slice cultures.

    Science.gov (United States)

    Inada, Chikako; Thi Le, Xoan; Tsuneyama, Koichi; Fujiwara, Hironori; Miyata, Takeshi; Matsumoto, Kinzo

    2013-01-15

    This study aimed to investigate a recuing role of cholinergic systems in the excitotoxicity-induced hippocampal cell damage. Organotypic hippocampal slice cultures (OHSCs) were prepared from 7-day-old mice and exposed to N-methyl-d-aspartate (NMDA) for 24h. After washing out the NMDA, OHSCs were incubated in medium containing test drugs for 0-6 days. Hippocampal cell damage was evaluated by propidium iodide staining, immunofluorescence, and Western blotting. NMDA (1-10 μM) dose-dependently damaged hippocampal cells. The toxic effect of 3 μM NMDA was also observed at 3-6 days, even after washing out NMDA, and was blocked by MK-801 from day 3 to day 6. Post-treatments with tacrine, donepezil, and galantamine reduced the NMDA-induced long-lasting hippocampal cell damage. The effect of tacrine was induced in a manner dependent on the incubation period after NMDA treatment and was confirmed by Nissl staining and immunostaining with NeuN, a marker of mature neurons. The effect of tacrine was attenuated by scopolamine and a muscarinic M(1) receptor antagonist, pirenzepine, but not by a muscarinic M(3) receptor antagonist, darifenacin, or a nicotinic receptor antagonist, mecamylamine. The protein kinase C inhibitor Ro-31-8220 abolished the effect of tacrine. The pretreatment with 3 μM NMDA had no effect on the expression level of presynaptic cholinergic markers, choline acetyltransferase and vesicular acetylcholine transporter, in OHSCs. These results suggest that a low concentration of NMDA causes long-lasting hippocampal cell damage and that endogenous acetylcholine plays, via muscarinic M(1) receptor, a rescuing role in the excitotoxicity-induced long-lasting hippocampal cell damage. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Synergistic antidepressant-like effect of the joint administration of caffeine and NMDA receptor ligands in the forced swim test in mice.

    Science.gov (United States)

    Serefko, Anna; Szopa, Aleksandra; Wlaź, Aleksandra; Wośko, Sylwia; Wlaź, Piotr; Poleszak, Ewa

    2016-04-01

    The optimal treatment of depressed patients remains one of the most important challenges concerning depression. The identification of the best treatment strategies and development of new, safer, and more effective agents are crucial. The glutamatergic system seems to be a promising drug target, and consequently the use of the NMDA receptor ligands, particularly in co-administration with other substances exerting the antidepressant activity, has emerged among the new ideas. The objective of this study was to examine the effect of caffeine on the performance of mice treated with various NMDA modulators in the forced swim test. We demonstrated a significant interaction between caffeine (5 mg/kg) and the following NMDA receptor ligands: MK-801 (an antagonist binding in the ion channel, 0.05 mg/kg), CGP 37849 (an antagonist of the glutamate site, 0.312 mg/kg), L-701,324 (an antagonist of the glycine site, 1 mg/kg), and D-cycloserine (a high-efficacy partial agonist of the glycine site, 2.5 mg/kg), while the interaction between caffeine and the inorganic modulators, i.e., Zn(2+) (2.5 mg/kg) and Mg(2+) (10 mg/kg), was not considered as significant. Based on the obtained results, the simultaneous blockage of the adenosine and NMDA receptors may be a promising target in the development of new antidepressants.

  18. Approximate design theory for a simple block design with random block effects

    OpenAIRE

    Christof, Karin

    1985-01-01

    Approximate design theory for a simple block design with random block effects / K. Christof ; F. Pukelsheim. - In: Linear statistical inference / ed. by T. Calinski ... - Berlin u. a. : Springer, 1985. - S. 20-28. - (Lecture notes in statistics ; 35)

  19. The effect of hippocampal NMDA receptor blockade by MK-801 on cued fear extinction.

    Science.gov (United States)

    Zhang, Bo; Li, Chuan-Yu; Wang, Xiu-Song

    2017-08-14

    Extinction of conditioned fear has been suggested to be a new form of learning instead of erasure of what was originally learned, and the process is NMDA (N-methyl d-aspartate) receptor (NMDAR) dependent. Most of studies have so far revealed the important roles of NMDARs in the amygdala and medial prefrontal cortex (mPFC) in cued fear extinction. Although the ventral hippocampus has intimately reciprocal connections with the amygdala and mPFC, the role of its NMDARs in cued fear extinction remains unclear. The present experiment explored the issue by bilateral pre-extinction microinjection of the noncompetitive NMDAR antagonist MK-801 into the ventral hippocampus. Four groups of rats were given habituation, tone cued fear conditioning, fear extinction training and extinction test. Prior to extinction training, rats received bilateral infusions of either MK-801 (1.5, 3, or 6μg/0.5μl) or saline. Our results showed that MK-801 reduced freezing on the first trial of extinction training with no impact on within-session acquisition of extinction, and that the lower doses of MK-801 resulted in increased freezing on the extinction retrieval test. These findings suggest that ventral hippocampal NMDARs are necessary for the consolidation of tone cued fear extinction. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Recovery of NMDA receptor currents from MK-801 blockade is accelerated by Mg2+ and memantine under conditions of agonist exposure.

    Science.gov (United States)

    McKay, Sean; Bengtson, C Peter; Bading, Hilmar; Wyllie, David J A; Hardingham, Giles E

    2013-11-01

    MK-801 is a use-dependent NMDA receptor open channel blocker with a very slow off-rate. These properties can be exploited to 'pre-block' a population of NMDARs, such as synaptic ones, enabling the selective activation of a different population, such as extrasynaptic NMDARs. However, the usefulness of this approach is dependent on the stability of MK-801 blockade after washout. We have revisited this issue, and confirm that recovery of NMDAR currents from MK-801 blockade is enhanced by channel opening by NMDA, and find that it is further increased when Mg(2+) is also present. In the presence of Mg(2+), 50% recovery from MK-801 blockade is achieved after 10' of 100 μM NMDA, or 30' of 15 μM NMDA exposure. In Mg(2+)-free medium, NMDA-induced MK-801 dissociation was found to be much slower. Memantine, another PCP-site antagonist, could substitute for Mg(2+) in accelerating the unblock of MK-801 in the presence of NMDA. This suggests a model whereby, upon dissociation from its binding site in the pore, MK-801 is able to re-bind in a process antagonized by Mg(2+) or another PCP-site antagonist. Finally we show that even when all NMDARs are pre-blocked by MK-801, incubation of neurons with 100 μM NMDA in the presence of Mg(2+) for 2.5 h triggers sufficient unblocking to kill >80% of neurons. We conclude that while synaptic MK-801 'pre-block' protocols are useful for pharmacologically assessing synaptic vs. extrasynaptic contributions to NMDAR currents, or studying short-term effects, it is problematic to use this technique to attempt to study the effects of long-term selective extrasynaptic NMDAR activation. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. GLYX-13, an NMDA receptor glycine site functional partial agonist enhances cognition and produces antidepressant effects without the psychotomimetic side effects of NMDA receptor antagonists.

    Science.gov (United States)

    Moskal, Joseph R; Burch, Ronald; Burgdorf, Jeffrey S; Kroes, Roger A; Stanton, Patric K; Disterhoft, John F; Leander, J David

    2014-02-01

    The N-methyl-d-aspartate receptor-ionophore complex plays a key role in learning and memory and has efficacy in animals and humans with affective disorders. GLYX-13 is an N-methyl-d-aspartate receptor (NMDAR) glycine-site functional partial agonist and cognitive enhancer that also shows rapid antidepressant activity without psychotomimetic side effects. The authors review the mechanism of action of GLYX-13 that was investigated in preclinical studies and evaluated in clinical studies. Specifically, the authors review its pharmacology, pharmacokinetics, and drug safety that were demonstrated in clinical studies. NMDAR full antagonists can produce rapid antidepressant effects in treatment-resistant subjects; however, they are often accompanied by psychotomimetic effects that make chronic use outside of a clinical trial inpatient setting problematic. GLYX-13 appears to exert its antidepressant effects in the frontal cortex via NMDAR-triggered synaptic plasticity. Understanding the mechanistic underpinning of GLYX-13's antidepressant action should provide both novel insights into the role of the glutamatergic system in depression and identify new targets for therapeutic development.

  2. Nucleon effective mass effects on the Pauli-blocking function

    International Nuclear Information System (INIS)

    Pina, S.R. de; Mesa, J.; Deppman, A.; Arruda-Neto, J.D.T.; Duarte, S.B.; Oliveira, E.C. de; Tavares, O.A.P.; Medeiros, E.L.; Goncalves, M.; Paiva, E. de

    2002-01-01

    The effects of nucleon effective mass on the Pauli-blocking function are worked out. We have shown that such effects on the quasi-deuteron mechanism of photonuclear absorption are rather relevant. The Pauli-blocking function has been evaluated by applying a Monte Carlo calculation particularly suitable for simulation of intranuclear cascade processes of intermediate-energy nuclear reactions. The nucleon binding in the photonuclear absorption mechanism is taken into account accordingly. (author)

  3. Involvement of ERK in NMDA receptor-independent cortical neurotoxicity of hydrogen sulfide

    International Nuclear Information System (INIS)

    Kurokawa, Yuko; Sekiguchi, Fumiko; Kubo, Satoko; Yamasaki, Yoshiko; Matsuda, Sachi; Okamoto, Yukari; Sekimoto, Teruki; Fukatsu, Anna; Nishikawa, Hiroyuki; Kume, Toshiaki; Fukushima, Nobuyuki; Akaike, Akinori; Kawabata, Atsufumi

    2011-01-01

    Highlights: ► Hydrogen sulfide causes NMDA receptor-independent neurotoxicity in mouse fetal cortical neurons. ► Activation of ERK mediates the toxicity of hydrogen sulfide. ► Apoptotic mechanisms are involved in the hydrogen-induced cell death. -- Abstract: Hydrogen sulfide (H 2 S), a gasotransmitter, exerts both neurotoxicity and neuroprotection, and targets multiple molecules including NMDA receptors, T-type calcium channels and NO synthase (NOS) that might affect neuronal viability. Here, we determined and characterized effects of NaHS, an H 2 S donor, on cell viability in the primary cultures of mouse fetal cortical neurons. NaHS caused neuronal death, as assessed by LDH release and trypan blue staining, but did not significantly reduce the glutamate toxicity. The neurotoxicity of NaHS was resistant to inhibitors of NMDA receptors, T-type calcium channels and NOS, and was blocked by inhibitors of MEK, but not JNK, p38 MAP kinase, PKC and Src. NaHS caused prompt phosphorylation of ERK and upregulation of Bad, followed by translocation of Bax to mitochondria and release of mitochondrial cytochrome c, leading to the nuclear condensation/fragmentation. These effects of NaHS were suppressed by the MEK inhibitor. Our data suggest that the NMDA receptor-independent neurotoxicity of H 2 S involves activation of the MEK/ERK pathway and some apoptotic mechanisms.

  4. Involvement of ERK in NMDA receptor-independent cortical neurotoxicity of hydrogen sulfide

    Energy Technology Data Exchange (ETDEWEB)

    Kurokawa, Yuko; Sekiguchi, Fumiko; Kubo, Satoko; Yamasaki, Yoshiko; Matsuda, Sachi; Okamoto, Yukari; Sekimoto, Teruki; Fukatsu, Anna; Nishikawa, Hiroyuki [Division of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan); Kume, Toshiaki [Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-cho, Sakyo-ku, Kyoto 606-8501 (Japan); Fukushima, Nobuyuki [Division of Molecular Neurobiology, Department of Life Sciences, Kinki University School of Science and Engineering, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan); Akaike, Akinori [Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-cho, Sakyo-ku, Kyoto 606-8501 (Japan); Kawabata, Atsufumi, E-mail: kawabata@phar.kindai.ac.jp [Division of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan)

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer Hydrogen sulfide causes NMDA receptor-independent neurotoxicity in mouse fetal cortical neurons. Black-Right-Pointing-Pointer Activation of ERK mediates the toxicity of hydrogen sulfide. Black-Right-Pointing-Pointer Apoptotic mechanisms are involved in the hydrogen-induced cell death. -- Abstract: Hydrogen sulfide (H{sub 2}S), a gasotransmitter, exerts both neurotoxicity and neuroprotection, and targets multiple molecules including NMDA receptors, T-type calcium channels and NO synthase (NOS) that might affect neuronal viability. Here, we determined and characterized effects of NaHS, an H{sub 2}S donor, on cell viability in the primary cultures of mouse fetal cortical neurons. NaHS caused neuronal death, as assessed by LDH release and trypan blue staining, but did not significantly reduce the glutamate toxicity. The neurotoxicity of NaHS was resistant to inhibitors of NMDA receptors, T-type calcium channels and NOS, and was blocked by inhibitors of MEK, but not JNK, p38 MAP kinase, PKC and Src. NaHS caused prompt phosphorylation of ERK and upregulation of Bad, followed by translocation of Bax to mitochondria and release of mitochondrial cytochrome c, leading to the nuclear condensation/fragmentation. These effects of NaHS were suppressed by the MEK inhibitor. Our data suggest that the NMDA receptor-independent neurotoxicity of H{sub 2}S involves activation of the MEK/ERK pathway and some apoptotic mechanisms.

  5. Effects of curcumin and tannic acid on the aluminum- and lead-induced oxidative neurotoxicity and alterations in NMDA receptors.

    Science.gov (United States)

    Tüzmen, Münire Nalan; Yücel, Nilgün Candan; Kalburcu, Tülden; Demiryas, Nazan

    2015-02-01

    Exposure to aluminum (Al) and lead (Pb) can cause brain damage. Also, Pb and Al exposure alters N-methyl-d-aspartate receptor (NMDAR) subunit expression. Polyphenols such as tannic acid and curcumin are very efficient chelator for metals. The effects of curcumin and tannic acid (polyphenols) on Al(3+)- and Pb(2+)-induced oxidative stress were examined by investigating lipid peroxidation (LPO) levels, antioxidant enzyme activities, acetyl cholinesterase (AChE) activity and also NMDA receptor subunits 2A and 2B concentrations in the brain tissue of rats sub-chronically. Rats were divided into seven groups as control, Al, Pb, aluminum-tannic acid treatment (AlT), aluminum-curcumin treatment (AlC), lead-tannic acid treatment (PbT) and lead-curcumin treatment (PbC). After 16 weeks of treatment, LPO levels in the brain and hippocampus were higher in Al(3+)-exposed rats than that of Pb(2+)-exposed group. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in brain tissue of Al- and Pb-exposed rats increased significantly compared with control, while catalase (CAT) and AChE activities decreased. It was observed that metal exposure affected NR2A concentrations more than NR2B concentrations and also that polyphenol treatments increased these receptor protein concentrations.

  6. Activation of D1-like dopamine receptors increases the NMDA-induced gain modulation through a PKA-dependent pathway in the premotor nucleus of adult zebra finches.

    Science.gov (United States)

    Wang, Songhua; Liao, Congshu; Meng, Wei; Huang, Qingyao; Li, Dongfeng

    2015-03-04

    Interaction between dopamine (DA) and N-methyl-d-aspartate (NMDA) in the brain plays an important role in learning and memory. In the songbirds, the premotor robust nucleus of the arcopallium (RA) receives excitatory glutamatergic inputs from the high vocal center (HVC) and lateral magnocellular nucleus of the anterior nidopallium (LMAN), as well as dopaminergic inputs mostly from the periaqueductal gray (PAG) and ventral tegmental area (VTA). In zebra finch, DA potentiates the excitability of projection neurons in the RA through activation of D1-like dopamine receptors (D1 receptors). The relationship between D1 receptors and NMDA in the RA projection neurons is essentially unknown. Our previous work showed that NMDA can induce gain modulation in the RA projection neurons. Here, using the whole-cell current-clamp recording from brain slices of male zebra finches, we observed whether D1 receptors regulate the NMDA-induced gain modulation in the RA projection neurons. Our results showed that activation of D1 receptors further increased the slope (gain) of the firing frequency-injected current (f-I) relationship induced by NMDA in the RA projection neurons. Blocking D1 receptors had no effect on the NMDA-induced gain modulation in the RA projection neurons. The enhanced effects of D1 receptors agonists were blocked by protein kinase A (PKA) inhibitors. Our results suggest that activation of D1 receptors can increase the NMDA-induced gain modulation through a PKA-dependent pathway. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Preclinical anticonvulsant and neuroprotective profile of 8319, a non-competitive NMDA antagonist

    International Nuclear Information System (INIS)

    Fielding, S.; Wilker, J.C.; Chernack, J.; Ramirez, V.; Wilmot, C.A.; Martin, L.L.; Payack, J.F.; Cornfeldt, M.L.; Rudolphi, K.A.; Rush, D.K.

    1990-01-01

    8319, ((+-)-2-Amino-N-ethyl-alpha-(3-methyl-2-thienyl)benzeneethanamine 2HCl), is a novel compound with the profile of a non-competitive NMDA antagonist. The compound displaced [3H] TCP with high affinity (IC50 = 43 nM), but was inactive at the NMDA, benzodiazepine and GABA sites; in vivo, 8319 showed good efficacy as an anticonvulsant and potential neuroprotective agent. It blocked seizures induced by NMDLA, supramaximal electroshock, pentylenetetrazol (PTZ), picrotoxin, and thiosemicarbazide with ED50's of 1-20 mg/kg ip. As a neuroprotective agent, 8319 (30-100 mg/kg sc) prevented the death of dorsal hippocampal pyramidal cells induced by direct injection of 20 nmol NMDA. At 15 mg/kg ip, the compound was also effective against hippocampal neuronal necrosis induced via bilateral occlusion of the carotid arteries in gerbils. In summary, 8319 is a noncompetitive NMDA antagonist with good anticonvulsant activity and may possess neuroprotective properties useful in the treatment of brain ischemia

  8. Huntington's disease: a randomized, controlled trial using the NMDA-antagonist amantadine.

    Science.gov (United States)

    Verhagen Metman, L; Morris, M J; Farmer, C; Gillespie, M; Mosby, K; Wuu, J; Chase, T N

    2002-09-10

    To examine the acute effects of the NMDA receptor antagonist amantadine on motor and cognitive function in Huntington's disease (HD). Chorea in HD and in the levodopa-induced dyskinesias of PD may be clinically indistinguishable. In PD, hyperphosphorylation of NMDA receptors expressed on striatal medium spiny neurons contributes to peak-dose dyskinesias, and drugs that block these receptors can diminish chorea severity. Because these spiny neurons are the primary target of the neurodegenerative process in HD, sensitization of NMDA receptors on residual striatal neurons might also participate in the generation of motor dysfunction in HD. To evaluate this possibility, 24 patients with HD entered a double-blind placebo-controlled crossover study of amantadine with two 2-week arms. Chorea scores were lower with amantadine (usually 400 mg/d) than placebo, with a median reduction in extremity chorea at rest of 36% (p = 0.04) for all 22 evaluable patients and of 56% in the 10 individuals with the highest plasma drug levels. Improvement correlated with plasma amantadine concentrations (p = 0.01) but not CAG repeat length. Parkinsonian rating scores did not worsen and there was no consistent change in cognitive measures. Adverse event profile was benign. Results suggest that NMDA receptor supersensitivity may contribute to the clinical expression of choreiform dyskinesias in HD and that selective antagonists at that site can safely confer palliative benefit.

  9. NMDA Receptor Antagonists for Treatment of Depression

    Directory of Open Access Journals (Sweden)

    Zeynep Ates-Alagoz

    2013-04-01

    Full Text Available Depression is a psychiatric disorder that affects millions of people worldwide. Individuals battling this disorder commonly experience high rates of relapse, persistent residual symptoms, functional impairment, and diminished well-being. Medications have important utility in stabilizing moods and daily functions of many individuals. However, only one third of patients had considerable improvement with a standard antidepressant after 2 months and all patients had to deal with numerous side effects. The N-methyl-d-aspartate (NMDA receptor family has received special attention because of its critical role in psychiatric disorders. Direct targeting of the NMDA receptor could result in more rapid antidepressant effects. Antidepressant-like effects of NMDA receptor antagonists have been demonstrated in different animal models. MK-801 (a use-dependent channel blocker, and CGP 37849 (an NMDA receptor antagonist have shown antidepressant properties in preclinical studies, either alone or combined with traditional antidepressants. A recent development is use of ketamine clinically for refractory depression. The purpose of this review is to examine and analyze current literature on the role of NMDA receptor antagonists for treatment of depression and whether this is a feasible route in drug discovery.

  10. Activation of NMDA receptors thickens the postsynaptic density via proteolysis.

    Science.gov (United States)

    Fukunaga, Yuko; Nakajima, Eri; Hatano, Erika; Itoh, Sayaka; Kashino, Yasuhiro; Miyazawa, Atsuo

    2015-12-01

    The postsynaptic density (PSD) is a protein complex that is critical for synaptic transmission. Ultrastructural changes in the PSD are therefore likely to modify synaptic functions. In this study, we investigated the ultrastructural changes in the PSD in the hippocampal CA1 stratum radiatum following neuronal excitation. Oxygen-glucose deprivation-induced PSD thickening in hippocampal slice cultures was blocked by the N-methyl-d-aspartate (NMDA) receptor antagonist MK801. To gain more insight into the mechanisms underlying NMDA receptor-mediated PSD thickening, we assessed the area, length, and thickness of the PSD after NMDA treatment. The PSDs thickened with just 2 min of NMDA receptor stimulation, and this treatment was considered sublethal. When N-acetyl-leucyl-leucyl-norleucinal, an inhibitor of calpain, cathepsins, and the proteasome, was applied, NMDA-induced PSD thickening was abolished. Furthermore, the calcium-induced calcium release inhibitor, ryanodine, reduced NMDA receptor-mediated PSD thickening. These results suggest that NMDA receptor activation induces PSD thickening by proteolysis through intracellular calcium increase, including that induced by calcium. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  11. Interferon-gamma potentiates NMDA receptor signaling in spinal dorsal horn neurons via microglia-neuron interaction.

    Science.gov (United States)

    Sonekatsu, Mayumi; Taniguchi, Wataru; Yamanaka, Manabu; Nishio, Naoko; Tsutsui, Shunji; Yamada, Hiroshi; Yoshida, Munehito; Nakatsuka, Terumasa

    2016-01-01

    Glia-neuron interactions play an important role in the development of neuropathic pain. Expression of the pro-inflammatory cytokne →cytokine Interferon-gamma (IFNγ) is upregulated in the dorsal horn after peripheral nerve injury, and intrathecal IFNγ administration induces mechanical allodynia in rats. A growing body of evidence suggests that IFNγ might be involved in the mechanisms of neuropathic pain, but its effects on the spinal dorsal horn are unclear. We performed blind whole-cell patch-clamp recording to investigate the effect of IFNγ on postsynaptic glutamate-induced currents in the substantia gelatinosa neurons of spinal cord slices from adult male rats. IFNγ perfusion significantly enhanced the amplitude of NMDA-induced inward currents in substantia gelatinosa neurons, but did not affect AMPA-induced currents. The facilitation of NMDA-induced current by IFNγ was inhibited by bath application of an IFNγ receptor-selective antagonist. Adding the Janus activated kinase inhibitor tofacitinib to the pipette solution did not affect the IFNγ-induced facilitation of NMDA-induced currents. However, the facilitatory effect of IFNγ on NMDA-induced currents was inhibited by perfusion of the microglial inhibitor minocycline. These results suggest that IFNγ binds the microglial IFNγ receptor and enhances NMDA receptor activity in substantia gelatinosa neurons. Next, to identify the effector of signal transmission from microglia to dorsal horn neurons, we added an inhibitor of G proteins, GDP-β-S, to the pipette solution. In a GDP-β-S-containing pipette solution, IFNγ-induced potentiation of the NMDA current was significantly suppressed after 30 min. In addition, IFNγ-induced potentiation of NMDA currents was blocked by application of a selective antagonist of CCR2, and its ligand CCL2 increased NMDA-induced currents. Our findings suggest that IFNγ enhance the amplitude of NMDA-induced inward currents in substantia gelatinosa neurons via microglial

  12. Interferon-gamma potentiates NMDA receptor signaling in spinal dorsal horn neurons via microglia–neuron interaction

    Science.gov (United States)

    Sonekatsu, Mayumi; Yamanaka, Manabu; Nishio, Naoko; Tsutsui, Shunji; Yamada, Hiroshi; Yoshida, Munehito; Nakatsuka, Terumasa

    2016-01-01

    Background Glia–neuron interactions play an important role in the development of neuropathic pain. Expression of the pro-inflammatory cytokne →cytokine Interferon-gamma (IFNγ) is upregulated in the dorsal horn after peripheral nerve injury, and intrathecal IFNγ administration induces mechanical allodynia in rats. A growing body of evidence suggests that IFNγ might be involved in the mechanisms of neuropathic pain, but its effects on the spinal dorsal horn are unclear. We performed blind whole-cell patch-clamp recording to investigate the effect of IFNγ on postsynaptic glutamate-induced currents in the substantia gelatinosa neurons of spinal cord slices from adult male rats. Results IFNγ perfusion significantly enhanced the amplitude of NMDA-induced inward currents in substantia gelatinosa neurons, but did not affect AMPA-induced currents. The facilitation of NMDA-induced current by IFNγ was inhibited by bath application of an IFNγ receptor-selective antagonist. Adding the Janus activated kinase inhibitor tofacitinib to the pipette solution did not affect the IFNγ-induced facilitation of NMDA-induced currents. However, the facilitatory effect of IFNγ on NMDA-induced currents was inhibited by perfusion of the microglial inhibitor minocycline. These results suggest that IFNγ binds the microglial IFNγ receptor and enhances NMDA receptor activity in substantia gelatinosa neurons. Next, to identify the effector of signal transmission from microglia to dorsal horn neurons, we added an inhibitor of G proteins, GDP-β-S, to the pipette solution. In a GDP-β-S–containing pipette solution, IFNγ-induced potentiation of the NMDA current was significantly suppressed after 30 min. In addition, IFNγ-induced potentiation of NMDA currents was blocked by application of a selective antagonist of CCR2, and its ligand CCL2 increased NMDA-induced currents. Conclusion Our findings suggest that IFNγ enhance the amplitude of NMDA-induced inward currents in substantia

  13. EVALUATING THE NMDA-GLUTAMATE RECEPTOR AS A SITE OF ACTION FOR TOLUENE, IN VIVO

    Science.gov (United States)

    In vitro, toluene disrupts the function of NMDA-glutamate receptors, indicating that effects on NMDA receptor function may contribute to toluene neurotoxicity. NMDA-glutamate receptors are widely present in the visual system and contribute to pattern-elicited visual evoked potent...

  14. Humanin rescues cultured rat cortical neurons from NMDA-induced toxicity not by NMDA receptor.

    Science.gov (United States)

    Cui, Ai-Ling; Li, Jian-Zhong; Feng, Zhi-Bo; Ma, Guo-Lin; Gong, Liang; Li, Chun-Ling; Zhang, Ce; Li, Kefeng

    2014-01-01

    Excitatory neurotoxicity has been implicated in many pathological situations and there is no effective treatment available. Humanin is a 24-aa peptide cloned from the brain of patients with Alzheimer's disease (AD). In the present study, excitatory toxicity was induced by N-methyl-D-aspartate (NMDA) in primarily cultured rat cortical neurons. MTT assessment, lactate dehydrogenase (LDH) release, and calcein staining were employed to evaluate the protective activity of humanin on NMDA induced toxicity. The results suggested that NMDA (100 μmol/L, 2.5 hr) triggered neuronal morphological changes, lactate dehydrogenase (LDH) release (166% of the control), reduction of cell viability (about 50% of the control), and the decrease of living cell density (about 50% of the control). When pretreated with humanin, the toxicity was suppressed. The living cells' density of humanin treated group was similar to that of control. The cell viability was attenuated dose-dependently (IC50 = 0.132 nmol/L). The LDH release was also neutralized in a dose-dependent manner. In addition, the intracellular Ca(2+) overloading triggered by NMDA reverted quickly and humanin could not inhibit it. These findings indicate that humanin can rescue cortical neurons from NMDA-induced toxicity in rat but not through interfering with NMDA receptor directly.

  15. Humanin Rescues Cultured Rat Cortical Neurons from NMDA-Induced Toxicity Not by NMDA Receptor

    Directory of Open Access Journals (Sweden)

    Ai-Ling Cui

    2014-01-01

    Full Text Available Excitatory neurotoxicity has been implicated in many pathological situations and there is no effective treatment available. Humanin is a 24-aa peptide cloned from the brain of patients with Alzheimer’s disease (AD. In the present study, excitatory toxicity was induced by N-methyl-D-aspartate (NMDA in primarily cultured rat cortical neurons. MTT assessment, lactate dehydrogenase (LDH release, and calcein staining were employed to evaluate the protective activity of humanin on NMDA induced toxicity. The results suggested that NMDA (100 μmol/L, 2.5 hr triggered neuronal morphological changes, lactate dehydrogenase (LDH release (166% of the control, reduction of cell viability (about 50% of the control, and the decrease of living cell density (about 50% of the control. When pretreated with humanin, the toxicity was suppressed. The living cells’ density of humanin treated group was similar to that of control. The cell viability was attenuated dose-dependently (IC50 = 0.132 nmol/L. The LDH release was also neutralized in a dose-dependent manner. In addition, the intracellular Ca2+ overloading triggered by NMDA reverted quickly and humanin could not inhibit it. These findings indicate that humanin can rescue cortical neurons from NMDA-induced toxicity in rat but not through interfering with NMDA receptor directly.

  16. Pharmacological evidence for the involvement of the NMDA receptor and nitric oxide pathway in the antidepressant-like effect of lamotrigine in the mouse forced swimming test.

    Science.gov (United States)

    Ostadhadi, Sattar; Ahangari, Mohammad; Nikoui, Vahid; Norouzi-Javidan, Abbas; Zolfaghari, Samira; Jazaeri, Farahnaz; Chamanara, Mohsen; Akbarian, Reyhaneh; Dehpour, Ahmad-Reza

    2016-08-01

    Lamotrigine is an anticonvulsant agent that shows clinical antidepressant properties. The aim of the present study was to investigate the involvement of N-methyl-d-aspartate (NMDA) receptors and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) synthesis in possible antidepressant-like effect of lamotrigine in forced swimming test (FST) in mice. Intraperitoneal administration of lamotrigine (10mg/kg) decreased the immobility time in the FST (PNMDA (75mg/kg), l-arginine (750mg/kg, a substrate for nitric oxide synthase [NOS]) or sildenafil (5mg/kg, a phosphodiesterase [PDE] 5 inhibitor) reversed the antidepressant-like effect of lamotrigine (10mg/kg) in the FST. Injection of l-nitroarginine methyl ester (l-NAME, 10mg/kg, a non-specific NOS inhibitor), 7-nitroindazole (30mg/kg, a neuronal NOS inhibitor), methylene blue (20mg/kg, an inhibitor of both NOS and soluble guanylate cyclase [sGC]), or MK-801 (0.05mg/kg), ketamine (1mg/kg), and magnesium sulfate (10mg/kg) as NMDA receptor antagonists in combination with a sub-effective dose of lamotrigine (5mg/kg) diminished the immobility time of animals in the FST compared with either drug alone. None of the drugs produced significant effects on the locomotor activity in the OFT. Based on our findings, it is suggested that the antidepressant-like effect of lamotrigine might mediated through inhibition of either NMDA receptors or NO-cGMP synthesis. Copyright © 2016. Published by Elsevier Masson SAS.

  17. Effect of glycine site/NMDA receptor antagonist MRZ2/576 on the conditioned place preference and locomotor activity induced by morphine in mice*

    OpenAIRE

    Zhu, Yong-ping; Long, Zai-hao; Zheng, Ming-lan; Binsack, Ralf

    2006-01-01

    Objective: To study the effect of glycine site/NMDA (N-methyl-D-aspartate) receptor antagonist MRZ2/576 on the conditioned place preference (CPP) and locomotor activity induced by morphine in mice. Methods: Different doses (1.25, 2.5 and 5 mg/kg, i.p.) of MRZ2/576 were used to evaluate the effect of MRZ2/576 on the acquisition and expression of CPP induced by morphine (5 mg/kg) in mice. In addition, we examined the locomotor activity of mice in conditioning and testing phase of CPP paradigm. ...

  18. Cutaneous Sensory Block Area, Muscle-Relaxing Effect, and Block Duration of the Transversus Abdominis Plane Block

    DEFF Research Database (Denmark)

    Støving, Kion; Rothe, Christian; Rosenstock, Charlotte V

    2015-01-01

    and the abdominal muscle-relaxing effect. RESULTS: The lateral part of the cutaneous sensory block area was a median of 266 cm2 (interquartile range, 191-310 cm2) and the medial part 76 cm 2(interquartile range, 54-127 cm2). In all the volunteers, lateral wall muscle thickness decreased significantly by 9.2 mm (6...

  19. Glutamatergic induction of CREB phosphorylation and Fos expression in primary cultures of the suprachiasmatic hypothalamus in vitro is mediated by co-ordinate activity of NMDA and non-NMDA receptors.

    Science.gov (United States)

    Schurov, I L; McNulty, S; Best, J D; Sloper, P J; Hastings, M H

    1999-01-01

    Exposure of Syrian hamsters to light 1 h after lights-off rapidly (10 min) induced nuclear immunoreactivity (-ir) to the phospho-Ser133 form of the Ca2+/cAMP response element (CRE) binding protein (pCREB) in the retinorecipient zone of the suprachiasmatic nuclei (SCN). Light also induced nuclear Fos-ir in the same region of the SCN after 1 h. The glutamatergic N-methyl-D-aspartate (NMDA) receptor blocker MK801 attenuated the photic induction of both factors. To investigate glutamatergic regulation of pCREB and Fos further, tissue blocks and primary cultures of neonatal hamster SCN were examined by Western blotting and immunocytochemistry in vitro. On Western blots of SCN tissue, the pCREB-ir signal at 45 kDa was enhanced by glutamate or a mixture of glutamatergic agonists (NMDA, amino-methyl proprionic acid (AMPA), and Kainate (KA)), whereas total CREB did not change. Glutamate or the mixture of agonists also induced a 56 kDa band identified as Fos protein in SCN tissue. In dissociated cultures of SCN, glutamate caused a rapid (15 min) induction of nuclear pCREB-ir and Fos-ir (after 60 min) exclusively in neurones, both GABA-ir and others. Treatment with NMDA alone had no effect on pCREB-ir. AMPA alone caused a slight increase in pCREB-ir. However, kainate alone or in combination with NMDA and AMPA induced nuclear pCREB-ir equal to that induced by glutamate. The effects of glutamate on pCREB-ir and Fos-ir were blocked by antagonists of both NMDA (MK801) and AMPA/KA (NBQX) receptors. In the absence of extracellular Mg2+, MK801 blocked glutamatergic induction of Fos-ir. However, the AMPA/KA receptor antagonist was no longer effective at blocking glutamatergic induction of either Fos-ir or pCREB-ir, consistent with the model that glutamate regulates gene expression in the SCN by a co-ordinate action through both NMDA and AMPA/KA receptors. Glutamatergic induction of nuclear pCREB-ir in GABA-ir neurones was blocked by KN-62 an inhibitor of Ca2+/Calmodulin (Ca

  20. NMDA Receptor Modulators in the Treatment of Drug Addiction

    Directory of Open Access Journals (Sweden)

    M. Foster Olive

    2013-02-01

    Full Text Available Glutamate plays a pivotal role in drug addiction, and the N-methyl-D-aspartate (NMDA glutamate receptor subtype serves as a molecular target for several drugs of abuse. In this review, we will provide an overview of NMDA receptor structure and function, followed by a review of the mechanism of action, clinical efficacy, and side effect profile of NMDA receptor ligands that are currently in use or being explored for the treatment of drug addiction. These ligands include the NMDA receptor modulators memantine and acamprosate, as well as the partial NMDA agonist D-cycloserine. Data collected to date suggest that direct NMDA receptor modulators have relatively limited efficacy in the treatment of drug addiction, and that partial agonism of NMDA receptors may have some efficacy with regards to extinction learning during cue exposure therapy. However, the lack of consistency in results to date clearly indicates that additional studies are needed, as are studies examining novel ligands with indirect mechanisms for altering NMDA receptor function.

  1. Noncompetitive, Voltage-Dependent NMDA Receptor Antagonism by Hydrophobic Anions

    Science.gov (United States)

    Linsenbardt, Andrew J.; Chisari, Mariangela; Yu, Andrew; Shu, Hong-Jin; Zorumski, Charles F.

    2013-01-01

    NMDA receptor (NMDAR) antagonists are dissociative anesthetics, drugs of abuse, and are of therapeutic interest in neurodegeneration and neuropsychiatric disease. Many well-known NMDAR antagonists are positively charged, voltage-dependent channel blockers. We recently showed that the hydrophobic anion dipicrylamine (DPA) negatively regulates GABAA receptor function by a mechanism indistinguishable from that of sulfated neurosteroids. Because sulfated neurosteroids also modulate NMDARs, here we examined the effects of DPA on NMDAR function. In rat hippocampal neurons DPA inhibited currents gated by 300 µM NMDA with an IC50 of 2.3 µM. Neither onset nor offset of antagonism exhibited dependence on channel activation but exhibited a noncompetitive profile. DPA antagonism was independent of NMDAR subunit composition and was similar at extrasynaptic and total receptor populations. Surprisingly, similar to cationic channel blockers but unlike sulfated neurosteroids, DPA antagonism was voltage dependent. Onset and offset of DPA antagonism were nearly 10-fold faster than DPA-induced increases in membrane capacitance, suggesting that membrane interactions do not directly explain antagonism. Furthermore, voltage dependence did not derive from association of DPA with a site on NMDARs directly accessible to the outer membrane leaflet, assessed by DPA translocation experiments. Consistent with the expected lack of channel block, DPA antagonism did not interact with permeant ions. Therefore, we speculate that voltage dependence may arise from interactions of DPA with the inherent voltage dependence of channel gating. Overall, we conclude that DPA noncompetitively inhibits NMDA-induced current by a novel voltage-dependent mechanism and represents a new class of anionic NMDAR antagonists. PMID:23144238

  2. AMP kinase regulates K-ATP currents evoked by NMDA receptor stimulation in rat subthalamic nucleus neurons.

    Science.gov (United States)

    Shen, K-Z; Yakhnitsa, V; Munhall, A C; Johnson, S W

    2014-08-22

    Our lab recently showed that N-methyl-D-aspartate (NMDA) evokes ATP-sensitive K(+) (K-ATP) currents in subthalamic nucleus (STN) neurons in slices of the rat brain. Both K-ATP channels and 5'-adenosine monophosphate-activated protein kinase (AMPK) are considered cellular energy sensors because their activities are influenced by the phosphorylation state of adenosine nucleotides. Moreover, AMPK has been shown to regulate K-ATP function in a variety of tissues including pancreas, cardiac myocytes, and hypothalamus. We used whole-cell patch clamp recordings to study the effect of AMPK activation on K-ATP channel function in STN neurons in slices of the rat brain. We found that bath or intracellular application of the AMPK activators A769662 and PT1 augmented tolbutamide-sensitive K-ATP currents evoked by NMDA receptor stimulation. The effect of AMPK activators was blocked by the AMPK inhibitor dorsomorphin (compound C), and by STO609, an inhibitor of the upstream AMPK activator CaMKKβ. AMPK augmentation of NMDA-induced K-ATP current was also blocked by intracellular BAPTA and by inhibitors of nitric oxide synthase and guanylyl cyclase. However, A769662 did not augment currents evoked by the K-ATP channel opener diazoxide. In the presence of NMDA, A769662 inhibited depolarizing plateau potentials and burst firing, both of which could be antagonized by tolbutamide or dorsomorphin. These studies show that AMPK augments NMDA-induced K-ATP currents by a Ca(2+)-dependent process that involves nitric oxide and cGMP. By augmenting K-ATP currents, AMPK activation would be expected to dampen the excitatory effect of glutamate-mediated transmission in the STN. Published by Elsevier Ltd.

  3. Synthesis of pregnane 3-carboxylic acids via Pd-catalyzed alkoxycarbonylation and their effect on NMDA receptor activity

    Czech Academy of Sciences Publication Activity Database

    Šťastná, Eva; Chodounská, Hana; Pouzar, Vladimír; Borovská, Jiřina; Vyklický ml., Ladislav

    2011-01-01

    Roč. 76, č. 9 (2011), s. 1141-1161 ISSN 0010-0765 R&D Projects: GA ČR(CZ) GA203/08/1498; GA ČR(CZ) GA309/07/0271 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50110509 Keywords : neurosteroids * carboxylic acid * alkoxycarbonylation * steroids * NMDA receptor activity Subject RIV: CC - Organic Chemistry Impact factor: 1.283, year: 2011

  4. Region-selective effects of neuroinflammation and antioxidant treatment on peripheral benzodiazepine receptors and NMDA receptors in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Biegon, A.; Alvarado, M.; Budinger, T.F.; Grossman, R.; Hensley, K.; West, M.S.; Kotake, Y.; Ono, M.; Floyd, R.A.

    2001-12-10

    Following induction of acute neuroinflammation by intracisternal injection of endotoxin (lipopolysaccharide) in rats, quantitative autoradiography was used to assess the regional level of microglial activation and glutamate (NMDA) receptor binding. The possible protective action of the antioxidant phenyl-tert-butyl nitrone in this model was tested by administering the drug in the drinking water for 6 days starting 24 hours after endotoxin injection. Animals were killed 7 days post-injection and consecutive cryostat brain sections labeled with [3H]PK11195 as a marker of activated microglia and [125I]iodoMK801 as a marker of the open-channel, activated state of NMDA receptors. Lipopolysaccharide increased [3H]PK11195 binding in the brain, with the largest increases (2-3 fold) in temporal and entorhinal cortex, hippocampus, and substantia innominata. A significant (>50 percent) decrease in [125I]iodoMK801 binding was found in the same brain regions. Phenyl-tert-butyl nitrone treatment resulted in a partial inhibition ({approx}25 percent decrease) of the lipopolysaccharide-induced increase in [3H]PK11195 binding but completely reversed the lipopolysaccharide-induced decrease in [125I]iodoMK80 binding in the entorhinal cortex, hippocampus, and substantia innominata. Loss of NMDA receptor function in cortical and hippocampal regions may contribute to the cognitive deficits observed in diseases with a neuroinflammatory component, such as meningitis or Alzheimer's disease.

  5. Excitotoxic effects of non-NMDA receptor agonists in organotypic corticostriatal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, B W; Noraberg, J; Jakobsen, B

    1999-01-01

    The excitotoxic effects of the glutamate receptor agonists kainic acid (KA) and 2-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and the corresponding neuroprotective effects of the AMPA/KA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) were examined in c...

  6. Triheteromeric NMDA Receptors at Hippocampal Synapses

    Science.gov (United States)

    Tovar, Kenneth R.; McGinley, Matthew J.; Westbrook, Gary L.

    2013-01-01

    NMDA receptors are composed of two GluN1 (N1) and two GluN2 (N2) subunits. Constituent N2 subunits control the pharmacological and kinetic characteristics of the receptor. NMDA receptors in hippocampal or cortical neurons are often thought of as diheteromeric, i.e., containing only one type of N2 subunit. However, triheteromeric receptors with more than one type of N2 subunit also have been reported and the relative contribution of di- and triheteromeric NMDA receptors at synapses has been difficult to assess. Because wild-type hippocampal principal neurons express N1, N2A and N2B, we used cultured hippocampal principal neurons from N2A and N2B-knockout mice as templates for diheteromeric synaptic receptors. Summation of N1/N2B and N1/N2A excitatory postsynaptic currents could not account for the deactivation kinetics of wild-type excitatory postsynaptic currents (EPSCs) however. To make a quantitative estimate of NMDA receptor subtypes at wild-type synapses, we used the deactivation kinetics, as well as the effects of the competitive antagonist NVP-AAM077. Our results indicate that three types of NMDA receptors contribute to the wild-type EPSC, with at least two-thirds being triheteromeric receptors. Functional isolation of synaptic triheteromeric receptors revealed deactivation kinetics and pharmacology distinct from either diheteromeric receptor subtype. Because of differences in open probability, synaptic triheteromeric receptors outnumbered N1/N2A receptors by 5.8 to 1 and N1/N2B receptors by 3.2 to 1. Our results suggest that triheteromeric NMDA receptors must be either preferentially assembled or preferentially localized at synapses. PMID:23699525

  7. Excitotoxic effects of non-NMDA receptor agonists in organotypic corticostriatal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, B W; Noraberg, J; Jakobsen, B

    1999-01-01

    of the cytosolic enzyme lactate dehydrogenase (LDH) into the culture medium and loss of glutamic acid decarboxylase (GAD) activity in the tissue. Histological sections were also stained by the fluorescent dye Fluoro-Jade (FJ), for degenerating neurons and by immunocytochemical staining for gamma-aminobutyric acid......The excitotoxic effects of the glutamate receptor agonists kainic acid (KA) and 2-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and the corresponding neuroprotective effects of the AMPA/KA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) were examined...... with an established set of markers for neuronal cell damage appears to be a feasible model for studies of the neurotoxic and neuroprotective effects of glutamate receptor agonists and antagonists....

  8. Adrenoceptor blocking effects of arotinolol, a new combined alpha- and beta-adrenoceptor blocking agent.

    Science.gov (United States)

    Miyagishi, A; Nakahara, H; Hara, Y

    1984-10-01

    In isolated tissues and anesthetized animals, beta- and alpha-adrenoceptor blocking properties of arotinolol were studied in comparison with those of other typical adrenoceptor antagonists. The following order of beta-adrenoceptor blocking activities were obtained in isolated tissues: arotinolol = pindolol greater than propranolol = oxprenolol = alprenolol greater than or equal to labetalol for beta 1-adrenoceptors (guinea-pig right atrium) and pindolol = oxprenolol = arotinolol greater than propranolol greater than labetalol for beta 2-adrenoceptors (guinea-pig trachea). In anesthetized cats, arotinolol was about 9 and 25 times more potent than propranolol, about 30 and 100 times more potent than labetalol in blocking beta 1- and beta 2-adrenoceptors, respectively. Furthermore arotinolol showed a competitive antagonistic effect on phenylephrine-induced contraction of isolated rat aortic strips. The relative order of alpha 1-adrenoceptor blocking potencies was as follows: prazosin greater than phentolamine greater than labetalol greater than arotinolol = yohimbine. Presynaptic alpha 2-adrenoceptor blocking action of arotinolol was also assessed in isolated rat vas deferens and arotinolol was revealed to be a much weaker presynaptic alpha 2-adrenoceptor antagonist. In anesthetized rats arotinolol was 4-5 times less potent than labetalol and about 26 times less potent than phentolamine in blocking alpha 1-adrenoceptors. Thus, as for the selectivity for 2 subtypes of alpha-adrenoceptors, arotinolol showed a selectivity for alpha 1-adrenoceptors over presynaptic alpha 2-adrenoceptors.

  9. Methylphenidate enhances NMDA-receptor response in medial prefrontal cortex via sigma-1 receptor: a novel mechanism for methylphenidate action.

    Directory of Open Access Journals (Sweden)

    Chun-Lei Zhang

    Full Text Available Methylphenidate (MPH, commercially called Ritalin or Concerta, has been widely used as a drug for Attention Deficit Hyperactivity Disorder (ADHD. Noteworthily, growing numbers of young people using prescribed MPH improperly for pleasurable enhancement, take high risk of addiction. Thus, understanding the mechanism underlying high level of MPH action in the brain becomes an important goal nowadays. As a blocker of catecholamine transporters, its therapeutic effect is explained as being due to proper modulation of D1 and α2A receptor. Here we showed that higher dose of MPH facilitates NMDA-receptor mediated synaptic transmission via a catecholamine-independent mechanism, in layer V∼VI pyramidal cells of the rat medial prefrontal cortex (PFC. To indicate its postsynaptic action, we next found that MPH facilitates NMDA-induced current and such facilitation could be blocked by σ1 but not D1/5 and α2 receptor antagonists. And this MPH eliciting enhancement of NMDA-receptor activity involves PLC, PKC and IP3 receptor mediated intracellular Ca(2+ increase, but does not require PKA and extracellular Ca(2+ influx. Our additional pharmacological studies confirmed that higher dose of MPH increases locomotor activity via interacting with σ1 receptor. Together, the present study demonstrates for the first time that MPH facilitates NMDA-receptor mediated synaptic transmission via σ1 receptor, and such facilitation requires PLC/IP3/PKC signaling pathway. This novel mechanism possibly explains the underlying mechanism for MPH induced addictive potential and other psychiatric side effects.

  10. Heavy Resistance Training and Supplementation With the Alleged Testosterone Booster Nmda has No Effect on Body Composition, Muscle Performance, and Serum Hormones Associated With the Hypothalamo-Pituitary-Gonadal Axis in Resistance-Trained Males.

    Science.gov (United States)

    Willoughby, Darryn S; Spillane, Mike; Schwarz, Neil

    2014-01-01

    The effects of 28 days of heavy resistance training while ingesting the alleged testosterone-boosting supplement, NMDA, were determined on body composition, muscle strength, serum cortisol, prolactin, and hormones associated with the hypothalamo-pituitary- gonadal (HPG) axis. Twenty resistance-trained males engaged in 28 days of resistance training 4 times/wk while orally ingesting daily either 1.78 g of placebo (PLAC) or NMDA. Data were analyzed with separate 2 x 2 ANOVA (p training and supplementation. No changes were noted for total body water and fat mass in response to resistance training (p > 0.05) or supplementation (p > 0.05). In regard to total body mass and fat-free mass, however, each was significantly increased in both groups in response to resistance training (p 0.05). In both groups, lower-body muscle strength was significantly increased in response to resistance training (p 0.05). All serum hormones (total and free testosterone, LH, GnRH, estradiol, cortisol, prolactin) were unaffected by resistance training (p > 0.05) or supplementation (p > 0.05). The gonadal hormones and cortisol and prolactin were unaffected by 28 days of NMDA supplementation and not associated with the observed increases in muscle strength and mass. At the dose provided, NMDA had no effect on HPG axis activity or ergogenic effects in skeletal muscle. Key PointsIn response to 28 days of heavy resistance training and NMDA supplementation, similar increases in muscle mass and strength in both groups occurred; however, the increases were not different between supplement groups.The supplementation of NMDA had no preferential effect on augmenting testosterone or decreasing estrogen, cortisol, and prolactin.While resistance training was effective in increasing muscle mass and strength, it was not preferentially due to NMDA supplementation.At the dose provided, NMDA supplementation for 28 days combined with resistance training does not increases muscle mass and strength due to its

  11. Role of the alpha-adrenergic blocking effect in the acute hypotensive effect of beta-adrenergic blocking drugs with alpha-blocking activities in conscious SHR.

    Science.gov (United States)

    Nakahara, H; Nakazawa, M; Takeda, K; Imai, S

    1985-12-01

    Acute hypotensive effects and the mechanisms of three beta-adrenergic blocking drugs with alpha-blocking activity were studied in comparison with those of prazosin, propranolol and hydralazine in the conscious spontaneously hypertensive rat (SHR). Prazosin lowered the blood pressure dose-dependently and inhibited the pressor response to phenylephrine. Three beta-adrenergic blocking drugs with alpha-blocking activity, labetalol (30 mg/kg), arotinolol (100 mg/kg) and nipradilol (100 mg/kg) also lowered the blood pressure to the same extent as prazosin (0.3 mg/kg), but the inhibition of the pressor response to phenylephrine produced by them was disproportionately slight. Propranolol (100 mg/kg) did not lower the blood pressure. These results suggest that the acute hypotensive effects of three beta-adrenergic blocking drugs with alpha-blocking activity were attributable only partially to the alpha-adrenergic blocking effect; a mechanism or mechanisms other than the alpha-adrenergic blocking effect must be invoked to explain the acute hypotensive effect produced by lower doses of these drugs in the conscious SHR.

  12. Prolonged Exposure of Cortical Neurons to Oligomeric Amyloid-β Impairs NMDA Receptor Function Via NADPH Oxidase-Mediated ROS Production: Protective Effect of Green Tea (--Epigallocatechin-3-Gallate

    Directory of Open Access Journals (Sweden)

    Yan He

    2011-01-01

    Full Text Available Excessive production of Aβ (amyloid β-peptide has been shown to play an important role in the pathogenesis of AD (Alzheimer's disease. Although not yet well understood, aggregation of Aβ is known to cause toxicity to neurons. Our recent study demonstrated the ability for oligomeric Aβ to stimulate the production of ROS (reactive oxygen species in neurons through an NMDA (N-methyl-D-aspartate-dependent pathway. However, whether prolonged exposure of neurons to aggregated Aβ is associated with impairment of NMDA receptor function has not been extensively investigated. In the present study, we show that prolonged exposure of primary cortical neurons to Aβ oligomers caused mitochondrial dysfunction, an attenuation of NMDA receptor-mediated Ca2+ influx and inhibition of NMDA-induced AA (arachidonic acid release. Mitochondrial dysfunction and the decrease in NMDA receptor activity due to oligomeric Aβ are associated with an increase in ROS production. Gp91ds-tat, a specific peptide inhibitor of NADPH oxidase, and Mn(III-tetrakis(4-benzoic acid-porphyrin chloride, an ROS scavenger, effectively abrogated Aβ-induced ROS production. Furthermore, Aβ-induced mitochondrial dysfunction, impairment of NMDA Ca2+ influx and ROS production were prevented by pretreatment of neurons with EGCG [(–-epigallocatechin-3-gallate], a major polyphenolic component of green tea. Taken together, these results support a role for NADPH oxidase-mediated ROS production in the cytotoxic effects of Aβ, and demonstrate the therapeutic potential of EGCG and other dietary polyphenols in delaying onset or retarding the progression of AD.

  13. NMDA receptor antagonist ketamine impairs feature integration in visual perception

    NARCIS (Netherlands)

    Meuwese, Julia D. I.; van Loon, Anouk M.; Scholte, H. Steven; Lirk, Philipp B.; Vulink, Nienke C. C.; Hollmann, Markus W.; Lamme, Victor A. F.

    2013-01-01

    Recurrent interactions between neurons in the visual cortex are crucial for the integration of image elements into coherent objects, such as in figure-ground segregation of textured images. Blocking N-methyl-D-aspartate (NMDA) receptors in monkeys can abolish neural signals related to figure-ground

  14. A family of photoswitchable NMDA receptors

    Science.gov (United States)

    Berlin, Shai; Szobota, Stephanie; Reiner, Andreas; Carroll, Elizabeth C; Kienzler, Michael A; Guyon, Alice; Xiao, Tong; Trauner, Dirk; Isacoff, Ehud Y

    2016-01-01

    NMDA receptors, which regulate synaptic strength and are implicated in learning and memory, consist of several subtypes with distinct subunit compositions and functional properties. To enable spatiotemporally defined, rapid and reproducible manipulation of function of specific subtypes, we engineered a set of photoswitchable GluN subunits ('LiGluNs'). Photo-agonism of GluN2A or GluN2B elicits an excitatory drive to hippocampal neurons that can be shaped in time to mimic synaptic activation. Photo-agonism of GluN2A at single dendritic spines evokes spine-specific calcium elevation and expansion, the morphological correlate of LTP. Photo-antagonism of GluN2A alone, or in combination with photo-antagonism of GluN1a, reversibly blocks excitatory synaptic currents, prevents the induction of long-term potentiation and prevents spine expansion. In addition, photo-antagonism in vivo disrupts synaptic pruning of developing retino-tectal projections in larval zebrafish. By providing precise and rapidly reversible optical control of NMDA receptor subtypes, LiGluNs should help unravel the contribution of specific NMDA receptors to synaptic transmission, integration and plasticity. DOI: http://dx.doi.org/10.7554/eLife.12040.001 PMID:26929991

  15. A family of photoswitchable NMDA receptors.

    Science.gov (United States)

    Berlin, Shai; Szobota, Stephanie; Reiner, Andreas; Carroll, Elizabeth C; Kienzler, Michael A; Guyon, Alice; Xiao, Tong; Trauner, Dirk; Isacoff, Ehud Y

    2016-03-01

    NMDA receptors, which regulate synaptic strength and are implicated in learning and memory, consist of several subtypes with distinct subunit compositions and functional properties. To enable spatiotemporally defined, rapid and reproducible manipulation of function of specific subtypes, we engineered a set of photoswitchable GluN subunits ('LiGluNs'). Photo-agonism of GluN2A or GluN2B elicits an excitatory drive to hippocampal neurons that can be shaped in time to mimic synaptic activation. Photo-agonism of GluN2A at single dendritic spines evokes spine-specific calcium elevation and expansion, the morphological correlate of LTP. Photo-antagonism of GluN2A alone, or in combination with photo-antagonism of GluN1a, reversibly blocks excitatory synaptic currents, prevents the induction of long-term potentiation and prevents spine expansion. In addition, photo-antagonism in vivo disrupts synaptic pruning of developing retino-tectal projections in larval zebrafish. By providing precise and rapidly reversible optical control of NMDA receptor subtypes, LiGluNs should help unravel the contribution of specific NMDA receptors to synaptic transmission, integration and plasticity.

  16. Imaging the PCP site of the NMDA ion channel

    International Nuclear Information System (INIS)

    Waterhouse, Rikki N.

    2003-01-01

    The N-methyl-D-aspartate (NMDA) ion channel plays a role in neuroprotection, neurodegeneration, long-term potentiation, memory, and cognition. It is implicated in the pathophysiology of several neurological and neuropsychiatric disorders including Parkinson's Disease, Huntington's Chorea, schizophrenia, alcoholism and stroke. The development of effective radiotracers for the study of NMDA receptors is critical for our understanding of their function, and their modulation by endogenousr substances or therapeutic drugs. Since the NMDA/PCP receptor lies within the channel, it is a unique target and is theoretically accessible only when the channel is in the active and 'open' state, but not when it is in the inactive or 'closed' state. The physical location of the NMDA/PCP receptor not only makes it an important imaging target but also complicates the development of suitable PET and SPECT radiotracers for this site. An intimate understanding of the biochemical, pharmacological, physiological and behavioral processes associated with the NMDA ion channel is essential to develop improved imaging agents. This review outlines progress made towards the development of radiolabeled agents for PCP sites of the NMDA ion channel. In addition, the animal and pharmacological models used for in vitro and in vivo assessment of NMDA receptor targeted agents are discussed

  17. Imaging the PCP site of the NMDA ion channel

    Energy Technology Data Exchange (ETDEWEB)

    Waterhouse, Rikki N. E-mail: rnw7@columbia.edu

    2003-11-01

    The N-methyl-D-aspartate (NMDA) ion channel plays a role in neuroprotection, neurodegeneration, long-term potentiation, memory, and cognition. It is implicated in the pathophysiology of several neurological and neuropsychiatric disorders including Parkinson's Disease, Huntington's Chorea, schizophrenia, alcoholism and stroke. The development of effective radiotracers for the study of NMDA receptors is critical for our understanding of their function, and their modulation by endogenousr substances or therapeutic drugs. Since the NMDA/PCP receptor lies within the channel, it is a unique target and is theoretically accessible only when the channel is in the active and 'open' state, but not when it is in the inactive or 'closed' state. The physical location of the NMDA/PCP receptor not only makes it an important imaging target but also complicates the development of suitable PET and SPECT radiotracers for this site. An intimate understanding of the biochemical, pharmacological, physiological and behavioral processes associated with the NMDA ion channel is essential to develop improved imaging agents. This review outlines progress made towards the development of radiolabeled agents for PCP sites of the NMDA ion channel. In addition, the animal and pharmacological models used for in vitro and in vivo assessment of NMDA receptor targeted agents are discussed.

  18. Stimulation of the N-methyl-D-aspartate receptor has a trophic effect on differentiating cerebellar granule cells

    DEFF Research Database (Denmark)

    Balázs, R; Hack, N; Jørgensen, Ole Steen

    1988-01-01

    -CAM contents indicated that NMDA rescued primarily nerve cells. The influence of NMDA in promoting cell survival was blocked by the receptor antagonist, 2-amino-5-phosphonovalerate. The effect depended both on the concentration of NMDA and on the degree of depolarization of cells, the affinity in the presence...... of 15 mM K+ being similar to that of NMDA receptor binding. The results attest a new role for excitatory amino acid transmitters by showing that they can exert a stage-dependent trophic action on developing nerve cells....

  19. NMDA Receptors on Dopaminoceptive Neurons Are Essential for Drug-Induced Conditioned Place Preference123

    Science.gov (United States)

    Tokarski, Krzysztof; Bobula, Bartosz; Zygmunt, Magdalena; Smutek, Magdalena; Kamińska, Katarzyna; Gołembiowska, Krystyna; Hess, Grzegorz; Przewlocki, Ryszard

    2016-01-01

    Abstract Plasticity of the brain’s dopamine system plays a crucial role in adaptive behavior by regulating appetitive motivation and the control of reinforcement learning. In this study, we investigated drug- and natural-reward conditioned behaviors in a mouse model in which the NMDA receptor-dependent plasticity of dopaminoceptive neurons was disrupted. We generated a transgenic mouse line with inducible selective inactivation of the NR1 subunit in neurons expressing dopamine D1 receptors (the NR1D1CreERT2 mice). Whole-cell recordings of spontaneous EPSCs on neurons in the nucleus accumbens confirmed that a population of neurons lacked the NMDA receptor-dependent component of the current. This effect was accompanied by impaired long-term potentiation in the nucleus accumbens and in the CA1 area of the ventral, but not the dorsal, hippocampus. Mutant mice did not differ from control animals when tested for pavlovian or instrumental conditioning. However, NR1D1CreERT2 mice acquired no preference for a context associated with administration of drugs of abuse. In the conditioned place preference paradigm, mutant mice did not spend more time in the context paired with cocaine, morphine, or ethanol, although these mice acquired a preference for sucrose jelly and an aversion to naloxone injections, as normal. Thus, we observed that the selective inducible ablation of the NMDA receptors specifically blocks drug-associated context memory with no effect on positive reinforcement in general. PMID:27294197

  20. Cellular prion protein and NMDA receptor modulation: protecting against excitotoxicity

    Directory of Open Access Journals (Sweden)

    Stefanie A.G. Black

    2014-08-01

    Full Text Available Although it is well established that misfolding of the cellular prion protein (PrPC into the beta-sheet-rich, aggregated scrapie conformation (PrPSc causes a variety of transmissible spongiform encephalopathies (TSEs, the physiological roles of PrPC are still incompletely understood. There is accumulating evidence describing the roles of PrPC in neurodegeneration and neuroinflammation. Recently, we identified a functional regulation of NMDA receptors by PrPC that involves formation of a physical protein complex between these proteins. Excessive NMDA receptor activity during conditions such as ischemia mediates enhanced Ca2+ entry into cells and contributes to excitotoxic neuronal death. In addition, NMDA receptors and/or PrPC play critical roles in neuroinflammation and glial cell toxicity. Inhibition of NMDA receptor activity protects against PrPSc-induced neuronal death. Moreover, in mice lacking PrPC, infarct size is increased after focal cerebral ischemia, and absence of PrPC increases susceptibility of neurons to NMDA receptor-dependent death. Recently, PrPC was found to be a receptor for oligomeric beta-amyloid (Abeta peptides, suggesting a role for PrPC in Alzheimer’s disease. Our recent findings suggest that Abeta peptides enhance NMDA receptor current by perturbing the normal copper- and PrPC-dependent regulation of these receptors. Here, we review evidence highlighting a role for PrPC in preventing NMDA receptor-mediated excitotoxicity and inflammation. There is a need for more detailed molecular characterization of PrPC-mediated regulation of NMDA receptors, such as determining which NMDA receptor subunits mediate pathogenic effects upon loss of PrPC-mediated regulation and identifying PrPC binding site(s on the receptor. This knowledge will allow development of novel therapeutic interventions for not only TSEs, but also for Alzheimer’s disease and other neurodegenerative disorders involving dysfunction of PrPC.

  1. Comparison of neuroprotective effects of erythropoietin (EPO) and carbamylerythropoietin (CEPO) against ischemia-like oxygen-glucose deprivation (OGD) and NMDA excitotoxicity in mouse hippocampal slice cultures

    DEFF Research Database (Denmark)

    Montero, Maria; Rom Poulsen, Frantz; Noraberg, Jens

    2007-01-01

    In addition to its well-known hematopoietic effects, erythropoietin (EPO) also has neuroprotective properties. However, hematopoietic side effects are unwanted for neuroprotection, underlining the need for EPO-like compounds with selective neuroprotective actions. One such compound, devoid...... of hematopoietic bioactivity, is the chemically modified, EPO-derivative carbamylerythropoietin (CEPO). For comparison of the neuroprotective effects of CEPO and EPO, we subjected organotypic hippocampal slice cultures to oxygen-glucose deprivation (OGD) or N-methyl-d-aspartate (NMDA) excitotoxicity. Hippocampal...... cultures. To elucidate a possible mechanism involved in EPO and CEPO neuroprotection against OGD, the integrity of alpha-II-spectrin cytoskeletal protein was studied. Both EPO and CEPO significantly reduced formation of spectrin cleavage products in the OGD model. We conclude that CEPO is at least...

  2. Projected BCS-Tamm-Dancoff approximation with blocking effect

    Science.gov (United States)

    Dias, H.; Krmpotić, F.

    1982-05-01

    The blocking effect is introduced through a canonical transformation in the projected BCS-Tamm-Dancoff approximation. It is suggested that the blocking effect may play an important role in the description of the low-lying states in odd-mass nuclei. Present address: Departamento de Física, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 1900 La Plata, Argentina. Member of Carrera de Investigador Científico, CONICET, Argentina. Sponsored by Financiadora de Estudos e Projetos (FINEP), Brasil.

  3. Concrete blocks' adverse effects on indoor air and recommended solutions

    International Nuclear Information System (INIS)

    Ruppersberger, J.S.

    1995-01-01

    Air infiltration through highly permeable concrete blocks can allow entry of various serious indoor air pollutants including radon. An easy approach to avoiding these pollutants is to select a less-air-permeable concrete block. Tests show that air permeability of concrete blocks can vary by a factor greater than 50 (0.63--35 standard L/min/m 2 at 3 Pa). The surface texture of the blocks correlates well with air permeability; test results of smoother, closed-surface-texture blocks were usually less air-permeable. During construction, air infiltration can be minimized by capping walls and carefully sealing around openings for utilities or other penetrations. Structures with indoor air-quality problems due to soil-gas entry can be mitigated more effectively with less coating material if the blocks have a closed surface texture. All coatings evaluated--cementaceous block filler (which has the lowest applied cost and is more than 99.5% effective), surface bonding cement, water-based epoxy, polysulfide vinyl acrylic, and latex (three coats)--were highly effective (more than 98%) in reducing air permeability when adequately applied. Coating selection should be influenced by expected service life, considering surface condition and cost

  4. Heavy Resistance Training and Supplementation With the Alleged Testosterone Booster Nmda has No Effect on Body Composition, Muscle Performance, and Serum Hormones Associated With the Hypothalamo-Pituitary-Gonadal Axis in Resistance-Trained Males

    Directory of Open Access Journals (Sweden)

    Darryn S. Willoughby

    2014-03-01

    Full Text Available The effects of 28 days of heavy resistance training while ingesting the alleged testosterone-boosting supplement, NMDA, were determined on body composition, muscle strength, serum cortisol, prolactin, and hormones associated with the hypothalamo-pituitary- gonadal (HPG axis. Twenty resistance-trained males engaged in 28 days of resistance training 4 times/wk while orally ingesting daily either 1.78 g of placebo (PLAC or NMDA. Data were analyzed with separate 2 x 2 ANOVA (p 0.05 or supplementation (p > 0.05. In regard to total body mass and fat-free mass, however, each was significantly increased in both groups in response to resistance training (p 0.05. In both groups, lower-body muscle strength was significantly increased in response to resistance training (p 0.05. All serum hormones (total and free testosterone, LH, GnRH, estradiol, cortisol, prolactin were unaffected by resistance training (p > 0.05 or supplementation (p > 0.05. The gonadal hormones and cortisol and prolactin were unaffected by 28 days of NMDA supplementation and not associated with the observed increases in muscle strength and mass. At the dose provided, NMDA had no effect on HPG axis activity or ergogenic effects in skeletal muscle.

  5. GLYX-13, a NMDA receptor glycine-site functional partial agonist, induces antidepressant-like effects without ketamine-like side effects.

    Science.gov (United States)

    Burgdorf, Jeffrey; Zhang, Xiao-lei; Nicholson, Katherine L; Balster, Robert L; Leander, J David; Stanton, Patric K; Gross, Amanda L; Kroes, Roger A; Moskal, Joseph R

    2013-04-01

    Recent human clinical studies with the NMDA receptor (NMDAR) antagonist ketamine have revealed profound and long-lasting antidepressant effects with rapid onset in several clinical trials, but antidepressant effects were preceded by dissociative side effects. Here we show that GLYX-13, a novel NMDAR glycine-site functional partial agonist, produces an antidepressant-like effect in the Porsolt, novelty induced hypophagia, and learned helplessness tests in rats without exhibiting substance abuse-related, gating, and sedative side effects of ketamine in the drug discrimination, conditioned place preference, pre-pulse inhibition and open-field tests. Like ketamine, the GLYX-13-induced antidepressant-like effects required AMPA/kainate receptor activation, as evidenced by the ability of NBQX to abolish the antidepressant-like effect. Both GLYX-13 and ketamine persistently (24 h) enhanced the induction of long-term potentiation of synaptic transmission and the magnitude of NMDAR-NR2B conductance at rat Schaffer collateral-CA1 synapses in vitro. Cell surface biotinylation studies showed that both GLYX-13 and ketamine led to increases in both NR2B and GluR1 protein levels, as measured by Western analysis, whereas no changes were seen in mRNA expression (microarray and qRT-PCR). GLYX-13, unlike ketamine, produced its antidepressant-like effect when injected directly into the medial prefrontal cortex (MPFC). These results suggest that GLYX-13 produces an antidepressant-like effect without the side effects seen with ketamine at least in part by directly modulating NR2B-containing NMDARs in the MPFC. Furthermore, the enhancement of 'metaplasticity' by both GLYX-13 and ketamine may help explain the long-lasting antidepressant effects of these NMDAR modulators. GLYX-13 is currently in a Phase II clinical development program for treatment-resistant depression.

  6. Subtype-Specific Agonists for NMDA Receptor Glycine Binding Sites

    DEFF Research Database (Denmark)

    Maolanon, Alex R.; Risgaard, Rune; Wang, Shuang Yan

    2017-01-01

    A series of analogues based on serine as lead structure were designed, and their agonist activities were evaluated at recombinant NMDA receptor subtypes (GluN1/2A-D) using two-electrode voltage-clamp (TEVC) electrophysiology. Pronounced variation in subunit-selectivity, potency, and agonist...... efficacy was observed in a manner that was dependent on the GluN2 subunit in the NMDA receptor. In particular, compounds 15a and 16a are potent GluN2C-specific superagonists at the GluN1 subunit with agonist efficacies of 398% and 308% compared to glycine. This study demonstrates that subunit......-selectivity among glycine site NMDA receptor agonists can be achieved and suggests that glycine-site agonists can be developed as pharmacological tool compounds to study GluN2C-specific effects in NMDA receptor-mediated neurotransmission....

  7. The involvement of NMDA receptor/NO/cGMP pathway in the antidepressant like effects of baclofen in mouse force swimming test.

    Science.gov (United States)

    Khan, Muhammad Imran; Ostadhadi, Sattar; Zolfaghari, Samira; Ejtemaei Mehr, Shahram; Hassanzadeh, Gholamreza; Dehpour, Ahmad-Reza

    2016-01-26

    In the current study, the involvement of N-methyl-d-aspartate receptor (NMDAR) and nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) system in the antidepressant-like effects of baclofen was evaluated by using animal model in forced swimming test. Followed by an open field test for the evaluation of locomotor activity, the immobility time for mice in force swimming test was recorded. Only the last four min was analyzed. Administration of Baclofen (0.5 and 1mg/kg, i.p.) reduced the immobility interval in the FST. Prior administration of l-arginine (750mg/kg, i.p.,) a nitric oxide synthase substrate or sildenafil (5mg/kg, i.p.) a phosphodiesterase 5 into mice suppressed the antidepressant-like activity of baclofen (1mg/kg, i.p.).Co-treatment of 7-nitroindazole (50mg/kg, i.p.,) an inhibitor of neuronal nitric oxide synthase, L-NAME (10mg/kg, i.p.,) a non-specific inhibitor of nitric oxide synthase or MK-801 (0.05mg/kg, i.p.) an NMDA receptor antagonist with subeffective dose of baclofen (0.1mg/kg, i.p.), reduced the immobility time in the FST as compared to the drugs when used alone. Co-administrated of lower doses of MK-801 (0.01mg/kg) or l-NAME (1mg/kg) failed to effect immobility time however, simultaneous administration of these two agents in same dose with subeffective dose of baclofen (0.1mg/kg, i.p.), minimized the immobility time in the FST. Thus, our results support the role of NMDA receptors and l-arginine-NO-GMP pathway in the antidepressant-like action of baclofen. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Protection by imidazol(ine) drugs and agmatine of glutamate-induced neurotoxicity in cultured cerebellar granule cells through blockade of NMDA receptor.

    Science.gov (United States)

    Olmos, G; DeGregorio-Rocasolano, N; Paz Regalado, M; Gasull, T; Assumpció Boronat, M; Trullas, R; Villarroel, A; Lerma, J; García-Sevilla, J A

    1999-07-01

    This study was designed to assess the potential neuroprotective effect of several imidazol(ine) drugs and agmatine on glutamate-induced necrosis and on apoptosis induced by low extracellular K+ in cultured cerebellar granule cells. Exposure (30 min) of energy deprived cells to L-glutamate (1-100 microM) caused a concentration-dependent neurotoxicity, as determined 24 h later by a decrease in the ability of the cells to metabolize 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) into a reduced formazan product. L-glutamate-induced neurotoxicity (EC50=5 microM) was blocked by the specific NMDA receptor antagonist MK-801 (dizocilpine). Imidazol(ine) drugs and agmatine fully prevented neurotoxicity induced by 20 microM (EC100) L-glutamate with the rank order (EC50 in microM): antazoline (13)>cirazoline (44)>LSL 61122 [2-styryl-2-imidazoline] (54)>LSL 60101 [2-(2-benzofuranyl) imidazole] (75)>idazoxan (90)>LSL 60129 [2-(1,4-benzodioxan-6-yl)-4,5-dihydroimidazole](101)>RX82 1002 (2-methoxy idazoxan) (106)>agmatine (196). No neuroprotective effect of these drugs was observed in a model of apoptotic neuronal cell death (reduction of extracellular K+) which does not involve stimulation of NMDA receptors. Imidazol(ine) drugs and agmatine fully inhibited [3H]-(+)-MK-801 binding to the phencyclidine site of NMDA receptors in rat brain. The profile of drug potency protecting against L-glutamate neurotoxicity correlated well (r=0.90) with the potency of the same compounds competing against [3H]-(+)-MK-801 binding. In HEK-293 cells transfected to express the NR1-1a and NR2C subunits of the NMDA receptor, antazoline and agmatine produced a voltage- and concentration-dependent block of glutamate-induced currents. Analysis of the voltage dependence of the block was consistent with the presence of a binding site for antazoline located within the NMDA channel pore with an IC50 of 10-12 microM at 0 mV. It is concluded that imidazol(ine) drugs and agmatine are

  9. NMDA receptor signaling: death or survival?

    OpenAIRE

    LUO, Tong; WU, Wei-Hua; CHEN, Bo-Shiun

    2011-01-01

    Glutamate-induced neuronal damage is mainly caused by overactivation of N-methyl-D-aspartate (NMDA) receptors. Conversely, normal physiological brain function and neuronal survival require adequate activation of NMDA receptors. Studies have revealed that NMDA receptor-induced neuronal death or survival is mediated through distinct subset of NMDA receptors triggering different intracellular signaling pathways. Here we discuss recent advances in the characterization of NMDA receptors in neurona...

  10. Regulation of NMDA Receptors by Phosphorylation

    OpenAIRE

    Chen, Bo-Shiun; Roche, Katherine W.

    2007-01-01

    N-methyl-D-aspartate (NMDA) receptors are critical for neuronal development and synaptic plasticity. The molecular mechanisms underlying the synaptic localization and functional regulation of NMDA receptors have been the subject of extensive studies. In particular, phosphorylation has emerged as a fundamental mechanism that regulates NMDA receptor trafficking and can alter the channel properties of NMDA receptors. Here we summarize recent advances in the characterization of NMDA receptor phos...

  11. Analgesic Effect Of Bilateral Subcostal Tap Block After Laparoscopic Cholecystectomy.

    Science.gov (United States)

    Khan, Karima Karam; Khan, Robyna Irshad

    2018-01-01

    Pain after laparoscopic cholecystectomy is mild to moderate in intensity. Several modalities are employed for achieving safe and effective postoperative analgesia, the benefits of which adds to the early recovery of the patients. As a part of multimodal analgesia, various approaches of Transversus abdominis plane (TAP) block has been used for management of parietal and incisional components of pain after laparoscopic cholecystectomy. This study was designed to compare the analgesic efficacy of two different approaches of ultrasound guided TAP block, i.e., Subcostal-TAP block technique with ultrasound guided Posterior-TAP block for postoperative pain management in patients undergoing laparoscopic cholecystectomy under general anaesthesia. In this double blinded randomized controlled study, consecutive nonprobability sampling was done and a total of 126 patients admitted for elective laparoscopic cholecystectomy fulfilling the inclusion criteria were selected. After induction of general anaesthesia, patients were randomized through draw method and received either ultrasound guided posterior TAP block with 0.375% bupivacaine (20ml volume) on each side of the abdomen or subcostal TAP block bilaterally with the same. Up to 24 hours postoperatively, static and dynamic numeric rating pain scores were assessed. We found statistically significant difference in mean static pain scores over 24 hours postoperatively in subcostal TAP group, suggesting improved analgesia. However, mean dynamic postoperative pain scores were comparable between the two groups. Whereas, patients in both groups were satisfied with pain management. Ultrasound guided subcostal TAP block provides better postoperative analgesia as compared to the Posterior TAP block in laparoscopic cholecystectomy. Otherwise both of the approaches improve patient outcomes towards early recovery and discharge from hospital.

  12. Effects of Mild Curvature on ANCOVA and Randomized Blocks.

    Science.gov (United States)

    Klockars, Alan J.; Potter, Nina Salcedo

    The type I error control and power of a number of analysis of covariance (ANCOVA) and randomized block (RB) designs with curvilinear data were studied for tests of the additive treatment effect and interaction. For tests of additive effects, the analysis was also conducted using systematic assignment to treatments and using random assignment with…

  13. Characterisation of the Redox Sensitive NMDA Receptor

    KAUST Repository

    Alzahrani, Ohood

    2016-05-01

    Glucose entry into the brain and its subsequent metabolism to L-lactate, regulated by astrocytes, plays a major role in synaptic plasticity and memory formation. A recent study has shown that L-lactate produced by the brain upon stimulation of glycolysis, and glycogen-derived L-lactate from astrocytes and its transport into neurons, is crucial for memory formation. A recent study revealed the molecular mechanisms that underlie the role of L-lactate in neuronal plasticity and long-term memory formation. L-lactate was shown to induce a cascade of molecular events via modulation of redox-sensitive N-Methyl-D-aspartate (NMDA) receptor activity that was mimicked by nicotinamide adenine dinucleotide hydride (NADH) co-enzyme. This indicated that changes in cellular redox state, following L-lactate transport inside the cells and its subsequent metabolism, production of NADH, and favouring a reduced state are the key effects of L-lactate. Therefore, we are investigating the role of L-lactate in modulating NMDA receptor function via redox modulatory sites. Accordingly, crucial redox-sensitive cysteine residues, Cys320 and Cys87, of the NR2A NMDA receptor subunit are mutated using site-directed mutation, transfected, and expressed in HEK293 cells. This cellular system will then be used to characterise and monitor its activity upon Llactate stimulation, compared to the wild type. This will be achieved by calcium imaging, using fluorescent microscopy. Our data shows that L-lactate potentiated NMDA receptor activity and increased intracellular calcium influx in NR1/NR2A wild type compared to the control condition (WT NR1/NR2A perfused with (1μM) glutamate and (1μM) glycine agonist only), showing faster response initiation and slower decay rate of the calcium signal to the baseline. Additionally, stimulating with L-lactate associated with greater numbers of cells having high fluorescent intensity (peak amplitude) compared to the control. Furthermore, L-lactate rescued the

  14. Kilohertz Electrical Stimulation Nerve Conduction Block: Effects of Electrode Material.

    Science.gov (United States)

    Patel, Yogi A; Kim, Brian S; Butera, Robert J

    2018-01-01

    Kilohertz electrical stimulation (KES) has enabled a novel new paradigm for spinal cord and peripheral nerve stimulation to treat a variety of neurological diseases. KES can excite or inhibit nerve activity and is used in many clinical devices today. However, the impact of different electrode materials on the efficacy of KES is unknown. We investigated the effect of different electrode materials and their respective charge injection mechanisms on KES nerve block thresholds using 20- and 40-kHz current-controlled sinusoidal KES waveforms. We evaluated the nerve block threshold and the power requirements for achieving an effective KES nerve block. In addition, we evaluated potential effects on the onset duration and recovery of normal conduction after delivery of KES. We found that thresholds and the onset and recovery of KES nerve block are not a function of the electrode material. In contrast, the power dissipation varies among electrode materials and is a function of the materials' properties at high frequencies. We conclude that materials with a proven track record of chronic stability, both for the tissue and electrode, are suitable for developing KES nerve block therapies.

  15. NMDA receptor structures reveal subunit arrangement and pore architecture.

    Science.gov (United States)

    Lee, Chia-Hsueh; Lü, Wei; Michel, Jennifer Carlisle; Goehring, April; Du, Juan; Song, Xianqiang; Gouaux, Eric

    2014-07-10

    N-methyl-d-aspartate (NMDA) receptors are Hebbian-like coincidence detectors, requiring binding of glycine and glutamate in combination with the relief of voltage-dependent magnesium block to open an ion conductive pore across the membrane bilayer. Despite the importance of the NMDA receptor in the development and function of the brain, a molecular structure of an intact receptor has remained elusive. Here we present X-ray crystal structures of the Xenopus laevis GluN1-GluN2B NMDA receptor with the allosteric inhibitor, Ro25-6981, partial agonists and the ion channel blocker, MK-801. Receptor subunits are arranged in a 1-2-1-2 fashion, demonstrating extensive interactions between the amino-terminal and ligand-binding domains. The transmembrane domains harbour a closed-blocked ion channel, a pyramidal central vestibule lined by residues implicated in binding ion channel blockers and magnesium, and a ∼twofold symmetric arrangement of ion channel pore loops. These structures provide new insights into the architecture, allosteric coupling and ion channel function of NMDA receptors.

  16. NMDA receptor structures reveal subunit arrangement and pore architecture

    Science.gov (United States)

    Lee, Chia-Hsueh; Lü, Wei; Michel, Jennifer Carlisle; Goehring, April; Du, Juan; Song, Xianqiang; Gouaux, Eric

    2014-01-01

    Summary N-methyl-d-aspartate (NMDA) receptors are Hebbian-like coincidence detectors, requiring binding of glycine and glutamate in combination with the relief of voltage-dependent magnesium block to open an ion conductive pore across the membrane bilayer. Despite the importance of the NMDA receptor in the development and function of the brain, a molecular structure of an intact receptor has remained elusive. Here we present x-ray crystal structures of the GluN1/GluN2B NMDA receptor with the allosteric inhibitor, Ro25-6981, partial agonists and the ion channel blocker, MK-801. Receptor subunits are arranged in a 1-2-1-2 fashion, demonstrating extensive interactions between the amino terminal and ligand binding domains. The transmembrane domains harbor a closed-blocked ion channel, a pyramidal central vestibule lined by residues implicated in binding ion channel blockers and magnesium, and a ~2-fold symmetric arrangement of ion channel pore loops. These structures provide new insights into the architecture, allosteric coupling and ion channel function of NMDA receptors. PMID:25008524

  17. CXCR4 and NMDA Receptors Are Functionally Coupled in Rat Hippocampal Noradrenergic and Glutamatergic Nerve Endings.

    Science.gov (United States)

    Di Prisco, Silvia; Olivero, Guendalina; Merega, Elisa; Bonfiglio, Tommaso; Marchi, Mario; Pittaluga, Anna

    2016-12-01

    Previous studies had shown that the HIV-1 capsidic glycoprotein gp120 (strain IIIB) modulates presynaptic release-regulating NMDA receptors on noradrenergic and glutamatergic terminals. This study aims to assess whether the chemokine CXC4 receptors (CXCR4s) has a role in the gp120-mediated effects. The effect of CXCL12, the endogenous ligand at CXCR4, on the NMDA-mediated releasing activity was therefore investigated. Rat hippocampal synaptosomes were preloaded with [ 3 H]noradrenaline ([ 3 H]NA) or [ 3 H]D-aspartate ([ 3 H]D-Asp) and acutely exposed to CXCL12, to NMDA or to both agonists. CXCL12, inactive on its own, facilitated the NMDA-evoked tritium release. The NMDA antagonist MK-801 abolished the NMDA/CXCL12-evoked tritium release of both radiolabelled tracers, while the CXCR4 antagonist AMD 3100 halved it, suggesting that rat hippocampal nerve endings possess presynaptic release-regulating CXCR4 receptors colocalized with NMDA receptors. Accordingly, Western blot analysis confirmed the presence of CXCR4 proteins in synaptosomal plasmamembranes. In both synaptosomal preparations, CXCL12-induced facilitation of NMDA-mediated release was dependent upon PLC-mediated src-induced events leading to mobilization of Ca 2+ from intraterminal IP 3 -sensitive stores Finally, the gp120-induced facilitation of NMDA-mediated release of [ 3 H]NA and [ 3 H]D-Asp was prevented by AMD 3100. We propose that CXCR4s are functionally coupled to NMDA receptors in rat hippocampal noradrenergic and glutamatergic terminals and account for the gp120-induced modulation of the NMDA-mediated central effects. The NMDA/CXCR4 cross-talk could have a role in the neuropsychiatric symptoms often observed in HIV-1 positive patients.

  18. Enhancement by interleukin-1β of AMPA and NMDA receptor-mediated currents in adult rat spinal superficial dorsal horn neurons.

    Science.gov (United States)

    Liu, Tao; Jiang, Chang-Yu; Fujita, Tsugumi; Luo, Shi-Wen; Kumamoto, Eiichi

    2013-03-28

    Proinflammatory cytokine interleukin-1β (IL-1β) released from spinal microglia plays an important role in the maintenance of acute and chronic pain states. However, the cellular basis of this action remains poorly understood. Using whole-cell patch-clamp recordings, we examined the action of IL-1β on AMPA- and NMDA-receptor-mediated currents recorded from substantia gelatinosa (SG) neurons of adult rat spinal cord slices which are key sites for regulating nociceptive transmission from the periphery. AMPA- and NMDA-induced currents were increased in peak amplitude by IL-1β in a manner different from each other in SG neurons. These facilitatory actions of IL-1β were abolished by IL-1 receptor (IL-1R) antagonist (IL-1ra), which by itself had no detectable effects on AMPA- and NMDA-induced currents. The AMPA- but not NMDA-induced current facilitated by IL-1β was recovered to control level 30 min after IL-1β washout and largely depressed in Na+-channel blocker tetrodotoxin-containing or nominally Ca2+-free Krebs solution. Minocycline, a microglia inhibitor, blocked the facilitatory effect of IL-1β on AMPA- but not NMDA-induced currents, where minocycline itself depressed NMDA- but had not any effects on AMPA-induced currents. IL-1β enhances AMPA and NMDA responses in SG neurons through IL-1R activation; the former but not latter action is reversible and due to an increase in neuronal activity in a manner dependent on extracellular Ca2+ and minocycline. It is suggested that AMPA and NMDA receptors are positively modulated by IL-1β in a manner different from each other; the former but not latter is mediated by a neurotransmitter released as a result of an increase in neuronal activity. Since IL-1β contributes to nociceptive behavior induced by peripheral nerve or tissue injury, the present findings also reveal an important cellular link between neuronal and glial cells in the spinal dorsal horn.

  19. Bidirectional effects of inhibiting or activating NMDA receptors on extinction after cocaine self-administration in rats

    Science.gov (United States)

    Hafenbreidel, Madalyn; Todd, Carolynn Rafa; Twining, Robert C.; Tuscher, Jennifer J.; Mueller, Devin

    2014-01-01

    Rationale Extinction of drug seeking is facilitated by NMDA receptor (NMDAr) agonists, but it remains unclear whether extinction is dependent on NMDAr activity. Objectives We investigated the necessity of NMDArs for extinction of cocaine seeking, and whether extinction altered NMDAr expression within extinction-related neuroanatomical loci. Methods Rats were trained to lever press for i.v. infusions of cocaine or sucrose reinforcement prior to extinction training or withdrawal. Results Administration of the NMDAr competitive antagonist CPP prior to four brief extinction sessions impaired subsequent extinction retention. In contrast, post-extinction administration of the NMDAr coagonist D-serine attenuated lever pressing across days as compared to saline administration, indicative of facilitated consolidation of extinction. Furthermore, expression of the NMDAr subunits, GluN2A and GluN2B, was not altered in the ventromedial prefrontal cortex. However, both GluN2A and GluN2B subunit expression in the nucleus accumbens was increased following cocaine self-administration, and this increased expression was relatively resistant to modulation by extinction. Conclusions Our findings demonstrate that extinction of cocaine seeking is bidirectionally mediated by NMDArs and suggest that selective modulation of NMDAr activity could facilitate extinction-based therapies for treatment of cocaine abuse. PMID:24847958

  20. Volume of the effect compartment in simulations of neuromuscular block

    NARCIS (Netherlands)

    Nigrovic, Vladimir; Proost, Johannes H.; Amann, Anton; Bhatt, Shashi B.

    2005-01-01

    Background: The study examines the role of the volume of the effect compartment in simulations of neuromuscular block (NMB) produced by nondepolarizing muscle relaxants. Methods: The molar amount of the postsynaptic receptors at the motor end plates in muscle was assumed constant; the apparent

  1. Ameliorative Effects of Neurolytic Celiac Plexus Block on Stress and ...

    African Journals Online (AJOL)

    Purpose: To investigate effects of neurolytic celiac plexus block (NCPB) on stress and inflammation in rats with partial hepatectomy (PH). Methods: A model of PH rat was established, and serum C-reactive protein (CRP); corticosterone (GC); adrenocorticotropin (ACTH); noradrenaline (NA); adrenalin (AD); aspartate ...

  2. Purkinje cell NMDA receptors assume a key role in synaptic gain control in the mature cerebellum

    Science.gov (United States)

    Piochon, Claire; Levenes, Carole; Ohtsuki, Gen; Hansel, Christian

    2010-01-01

    A classic view in cerebellar physiology holds that Purkinje cells do not express functional N-methyl-D-aspartate (NMDA) receptors and that, therefore, postsynaptic NMDA receptors are not involved in the induction of long-term depression (LTD) at parallel fiber (PF) to Purkinje cell synapses. Recently, it has been demonstrated that functional NMDA receptors are postsynaptically expressed at climbing fiber (CF) to Purkinje cell synapses in mice, reaching full expression levels at about 2 months after birth. Here, we show that in the mature mouse cerebellum LTD (induced by paired PF and CF activation), but not long-term potentiation (LTP; PF stimulation alone) at PF to Purkinje cell synapses is blocked by bath application of the NMDA receptor antagonist D-APV. A blockade of LTD, but not LTP, was also observed when the non-competitive NMDA channel blocker MK-801 was added to the patch-pipette saline, suggesting that postsynaptically expressed NMDA receptors are required for LTD induction. Using confocal calcium imaging, we show that CF-evoked calcium transients in dendritic spines are reduced in the presence of D-APV. This observation confirms that NMDA receptor signaling occurs at CF synapses, and suggests that NMDA receptor-mediated calcium transients at the CF input site might contribute to LTD induction. Finally, we performed dendritic patch-clamp recordings from rat Purkinje cells. Dendritically recorded CF responses were reduced when D-APV was bath-applied. Together, these data suggest that the late developmental expression of postsynaptic NMDA receptors at CF synapses onto Purkinje cells is associated with a switch towards an NMDA receptor-dependent LTD induction mechanism. PMID:21068337

  3. Are cellular phone blocking applications effective for novice teen drivers?

    Science.gov (United States)

    Creaser, Janet I; Edwards, Christopher J; Morris, Nichole L; Donath, Max

    2015-09-01

    Distracted driving is a significant concern for novice teen drivers. Although cellular phone bans are applied in many jurisdictions to restrict cellular phone use, teen drivers often report making calls and texts while driving. The Minnesota Teen Driver Study incorporated cellular phone blocking functions via a software application for 182 novice teen drivers in two treatment conditions. The first condition included 92 teens who ran a driver support application on a smartphone that also blocked phone usage. The second condition included 90 teens who ran the same application with phone blocking but which also reported back to parents about monitored risky behaviors (e.g., speeding). A third control group consisting of 92 novice teen drivers had the application and phone-based software installed on the phones to record cellular phone (but not block it) use while driving. The two treatment groups made significantly fewer calls and texts per mile driven compared to the control group. The control group data also demonstrated a higher propensity to text while driving rather than making calls. Software that blocks cellular phone use (except 911) while driving can be effective at mitigating calling and texting for novice teen drivers. However, subjective data indicates that some teens were motivated to find ways around the software, as well as to use another teen's phone while driving when they were unable to use theirs. Cellular phone bans for calling and texting are the first step to changing behaviors associated with texting and driving, particularly among novice teen drivers. Blocking software has the additional potential to reduce impulsive calling and texting while driving among novice teen drivers who might logically know the risks, but for whom it is difficult to ignore calling or texting while driving. Copyright © 2015 Elsevier Ltd and National Safety Council. All rights reserved.

  4. Pauli blocking and medium effects in nucleon knockout reactions

    International Nuclear Information System (INIS)

    Bertulani, C. A.; De Conti, C.

    2010-01-01

    We study medium modifications of the nucleon-nucleon (NN) cross sections and their influence on the nucleon knockout reactions. Using the eikonal approximation, we compare the results obtained with free NN cross sections with those obtained with a purely geometrical treatment of Pauli blocking and with NN obtained with more elaborated Dirac-Bruecker methods. The medium effects are parametrized in terms of the baryon density. We focus on symmetric nuclear matter, although the geometrical Pauli blocking also allows for the treatment of asymmetric nuclear matter. It is shown that medium effects can change the nucleon knockout cross sections and momentum distributions up to 10% in the energy range E lab =50-300 MeV/nucleon. The effect is more evident in reactions involving halo nuclei.

  5. The Effect of Intravenous Dexmedetomidine on Spinal Block and Sedation

    Directory of Open Access Journals (Sweden)

    Abdurrahman Ekici

    2015-03-01

    Material and Methods: Our randomised, double-blind study was applied to ASA I-III, 18-75 years old 50 patients scheduled for transurethral surgery. The patients were divided into two groups and spinal anesthesia with 5% levobupivacaine 12.5 mg was administered to all patients. Intravenous dexmedetomidine was received 1 and micro;g/kg for loading dose before 0.5 and micro;g/kg/hour infusion to Group D (n=25. Saline infusion was given 1 and micro;g/kg for loading dose before 0.5 and micro;g/kg/hour infusion to Group S (n=25. Systolic, diastolic and mean arterial pressure, heart rate, peripheral oxygen saturation values, pain and sedation score, the level and duration of motor and sensorial block, recovery and patient comfort score and side effects were recorded. Results: Time to reach maximum block level and duration of spinal anesthesia were longer in Group D than Group S. Sedation scores were significantly higher in Group D than Group S intraoperatively (except 1th minute and postoperatively 10th and 15th minutes. The incidence of side effects, postoperative recovery and patient comfort values were similar between the groups. Conclusion: We found that dexmedetomidine prolongs duration of motor block, provides safe and effective sedation without increasing the incidence of side effect in the patients under spinal anesthesia. [Cukurova Med J 2015; 40(1.000: 55-62

  6. Modulation of inhibitory activity markers by intermittent theta-burst stimulation in rat cortex is NMDA-receptor dependent.

    Science.gov (United States)

    Labedi, Adnan; Benali, Alia; Mix, Annika; Neubacher, Ute; Funke, Klaus

    2014-01-01

    Intermittent theta-burst stimulation (iTBS) applied via transcranial magnetic stimulation has been shown to increase cortical excitability in humans. In the rat brain it strongly reduced the number of neurons expressing the 67-kD isoform of the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD67) and those expressing the calcium-binding proteins parvalbumin (PV) and calbindin (CB), specific markers of fast-spiking (FS) and non-FS inhibitory interneurons, respectively, an indication of modified cortical inhibition. Since iTBS effects in humans have been shown to be NMDA receptor sensitive, we wondered whether the iTBS-induced changes in the molecular phenotype of interneurons may be also sensitive to glutamatergic synaptic transmission mediated by NMDA receptors. In a sham-controlled fashion, five iTBS-blocks of 600 stimuli were applied to rats either lightly anesthetized by only urethane or by an additional low (subnarcotic) or high dose of the NMDA receptor antagonist ketamine before immunohistochemical analysis. iTBS reduced the number of neurons expressing GAD67, PV and CB. Except for CB, a low dose of ketamine partially prevented these effects while a higher dose almost completely abolished the iTBS effects. Our findings indicate that iTBS modulates the molecular, and likely also the electric, activity of cortical inhibitory interneurons and that the modulation of FS-type but less that of non-FS-type neurons is mediated by NMDA receptors. A combination of iTBS with pharmacological interventions affecting distinct receptor subtypes may thus offer options to enhance its selectivity in modulating the activity of distinct cell types and preventing others from being modulated. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Functional NMDA receptors are expressed by both AII and A17 amacrine cells in the rod pathway of the mammalian retina.

    Science.gov (United States)

    Zhou, Yifan; Tencerová, Barbora; Hartveit, Espen; Veruki, Margaret L

    2016-01-01

    At many glutamatergic synapses, non-N-methyl-d-aspartate (NMDA) and NMDA receptors are coexpressed postsynaptically. In the mammalian retina, glutamatergic rod bipolar cells are presynaptic to two rod amacrine cells (AII and A17) that constitute dyad postsynaptic partners opposite each presynaptic active zone. Whereas there is strong evidence for expression of non-NMDA receptors by both AII and A17 amacrines, the expression of NMDA receptors by the pre- and postsynaptic neurons in this microcircuit has not been resolved. In this study, using patch-clamp recording from visually identified cells in rat retinal slices, we investigated the expression and functional properties of NMDA receptors in these cells with a combination of pharmacological and biophysical methods. Pressure application of NMDA did not evoke a response in rod bipolar cells, but for both AII and A17 amacrines, NMDA evoked responses that were blocked by a competitive antagonist (CPP) applied extracellularly and an open channel blocker (MK-801) applied intracellularly. NMDA-evoked responses also displayed strong Mg(2+)-dependent voltage block and were independent of gap junction coupling. With low-frequency application (60-s intervals), NMDA-evoked responses remained stable for up to 50 min, but with higher-frequency stimulation (10- to 20-s intervals), NMDA responses were strongly and reversibly suppressed. We observed strong potentiation when NMDA was applied in nominally Ca(2+)-free extracellular solution, potentially reflecting Ca(2+)-dependent NMDA receptor inactivation. These results indicate that expression of functional (i.e., conductance-increasing) NMDA receptors is common to both AII and A17 amacrine cells and suggest that these receptors could play an important role for synaptic signaling, integration, or plasticity in the rod pathway. Copyright © 2016 the American Physiological Society.

  8. A Metabotropic-Like Flux-Independent NMDA Receptor Regulates Ca2+ Exit from Endoplasmic Reticulum and Mitochondrial Membrane Potential in Cultured Astrocytes.

    Science.gov (United States)

    Montes de Oca Balderas, Pavel; Aguilera, Penélope

    2015-01-01

    Astrocytes were long thought to be only structural cells in the CNS; however, their functional properties support their role in information processing and cognition. The ionotropic glutamate N-methyl D-aspartate (NMDA) receptor (NMDAR) is critical for CNS functions, but its expression and function in astrocytes is still a matter of research and debate. Here, we report immunofluorescence (IF) labeling in rat cultured cortical astrocytes (rCCA) of all NMDAR subunits, with phenotypes suggesting their intracellular transport, and their mRNA were detected by qRT-PCR. IF and Western Blot revealed GluN1 full-length synthesis, subunit critical for NMDAR assembly and transport, and its plasma membrane localization. Functionally, we found an iCa2+ rise after NMDA treatment in Fluo-4-AM labeled rCCA, an effect blocked by the NMDAR competitive inhibitors D(-)-2-amino-5-phosphonopentanoic acid (APV) and Kynurenic acid (KYNA) and dependent upon GluN1 expression as evidenced by siRNA knock down. Surprisingly, the iCa2+ rise was not blocked by MK-801, an NMDAR channel blocker, or by extracellular Ca2+ depletion, indicating flux-independent NMDAR function. In contrast, the IP3 receptor (IP3R) inhibitor XestosponginC did block this response, whereas a Ryanodine Receptor inhibitor did so only partially. Furthermore, tyrosine kinase inhibition with genistein enhanced the NMDA elicited iCa2+ rise to levels comparable to those reached by the gliotransmitter ATP, but with different population dynamics. Finally, NMDA depleted the rCCA mitochondrial membrane potential (mΔψ) measured with JC-1. Our results demonstrate that rCCA express NMDAR subunits which assemble into functional receptors that mediate a metabotropic-like, non-canonical, flux-independent iCa2+ increase.

  9. Glutamate receptor properties of human mesencephalic neural progenitor cells: NMDA enhances dopaminergic neurogenesis in vitro.

    Science.gov (United States)

    Wegner, Florian; Kraft, Robert; Busse, Kathy; Schaarschmidt, Grit; Härtig, Wolfgang; Schwarz, Sigrid C; Schwarz, Johannes

    2009-10-01

    Human midbrain-derived neural progenitor cells (NPCs) may serve as a continuous source of dopaminergic neurons for the development of novel regenerative therapies in Parkinson's disease. However, the molecular and functional characteristics of glutamate receptors in human NPCs are largely unknown. Here, we show that differentiated human mesencepahlic NPCs display a distinct pattern of glutamate receptors. In whole-cell patch-clamp recordings, l-glutamate and NMDA elicited currents in 93% of NPCs after 3 weeks of differentiation in vitro. The concentration-response plots of differentiated NPCs yielded an EC(50) of 2.2 microM for glutamate and an EC(50) of 36 microM for NMDA. Glutamate-induced currents were markedly inhibited by memantine in contrast to 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) suggesting a higher density of functional NMDA than alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptors. NMDA-evoked currents and calcium signals were blocked by the NR2B-subunit specific antagonist ifenprodil indicating functional expression of NMDA receptors containing subunits NR1 and NR2B. In calcium imaging experiments, the blockade of voltage-gated calcium channels by verapamil abolished AMPA-induced calcium responses but only partially reduced NMDA-evoked transients suggesting the expression of calcium-impermeable, GluR2-containing AMPA receptors. Quantitative real-time PCR showed a predominant expression of subunits NR2A and NR2B (NMDA), GluR2 (AMPA), GluR7 (kainate), and mGluR3 (metabotropic glutamate receptor). Treatment of NPCs with 100 microM NMDA in vitro during proliferation (2 weeks) and differentiation (1 week) increased the amount of tyrosine hydroxylase-immunopositive cells significantly, which was reversed by addition of memantine. These data suggest that NMDA receptors in differentiating human mesencephalic NPCs are important regulators of dopaminergic neurogenesis in vitro.

  10. Prenatal exposure of testosterone prevents SDN-POA neurons of postnatal male rats from apoptosis through NMDA receptor.

    Science.gov (United States)

    Hsu, H K; Yang, R C; Shih, H C; Hsieh, Y L; Chen, U Y; Hsu, C

    2001-11-01

    The role of N-methyl-D-aspartate (NMDA) receptor in mediating the effect of testosterone exposure prenatally on neuronal apoptosis in the sexual dimorphic nucleus of the preoptic area (SDN-POA) of rats was studied. The endogenous testosterone was diminished by prenatal stress (PNS) or simulated by testosterone exposure (TE) to understand the effect of testosterone on NR(1) (a functional subunit protein of NMDA receptor) expression and neuronal apoptosis. To further study whether the testosterone, after being converted into estradiol, modulates NR(1) expression, 4-androstein-4-ol-3,17-dione (ATD; an aromatase inhibitor) was used to block the conversion of estradiol from testosterone. The expressions of the NR(1) mRNA and NR(1) subunit protein were quantified by RT-PCR and western blotting analysis, respectively. In addition, a noncompetitive antagonist of NMDA receptor, MK-801, was used to find out whether blockage of NMDA receptor affects the naturally occurring apoptosis in SDN-POA. The results showed the following. 1) Expression of perinatal NR(1) subunit protein in the central part of the medial preoptic area of male rats was significantly higher than that of females, especially on postnatal days 1 and 3. 2) The testosterone level of male fetuses on embryonic day 18 was significantly higher than that of females, while the testosterone level of TE females or PNS males was similar to that of intact males or intact females, respectively. 3) The apoptotic incidence of intact male rats was significantly less than that of females, and the apoptosis was stimulated by PNS in male or inhibited by TE in female. 4) The expression of NR(1) subunit protein could be inhibited by PNS or ATD-treatment in male, while stimulated by TE in female. 5) NR(1) mRNA showed no significant difference among intact male, PNS male, ATD-treated male, TE female and intact female rats. 6) The low apoptotic incidence of male rats was significantly increased when NMDA receptor was blocked by MK

  11. Effect of mitochondrial calcium uniporter blocking on human spermatozoa.

    Science.gov (United States)

    Bravo, A; Treulen, F; Uribe, P; Boguen, R; Felmer, R; Villegas, J V

    2015-08-01

    Calcium (Ca(2+) ) regulates a number of essential processes in spermatozoa. Ca(2+) is taken up by mitochondria via the mitochondrial calcium uniporter (mCU). Oxygen-bridged dinuclear ruthenium amine complex (Ru360) has been used to study mCU because it is a potent and specific inhibitor of this channel. In bovine spermatozoa, it has been demonstrated that mitochondrial calcium uptake inhibition adversely affects the capacitation process. It has been demonstrated in human spermatozoa that mCU blocking, through Ru360, prevents apoptosis; however, the contribution of the mCU to normal human sperm function has not been studied. Therefore, the aim of this study was to evaluate the effect of mCU blocking on human sperm function. Spermatozoa obtained from apparently healthy donors were incubated with 5 and 10 μm Ru360 for 4 h at 37 °C. Viability was assessed using propidium iodide staining; motility was determined by computer-aided sperm analysis, adenosine triphosphate (ATP) levels using a luminescence-based method, mitochondrial membrane potential (ΔΨm) using JC-1 staining and reactive oxygen species (ROS) production using dihydroethidium dye. Our results show that mCU blocking significantly reduced total sperm motility and ATP levels without affecting sperm viability, ΔΨm and ROS production. In conclusion, mCU contributes to the maintenance of sperm motility and ATP levels in human spermatozoa. © 2014 Blackwell Verlag GmbH.

  12. Metabotropic glutamate receptor 5 activation enhances tyrosine phosphorylation of the N-methyl-D-aspartate (NMDA) receptor and NMDA-induced cell death in hippocampal cultured neurons.

    Science.gov (United States)

    Takagi, Norio; Besshoh, Shintaro; Marunouchi, Tetsuro; Takeo, Satoshi; Tanonaka, Kouichi

    2012-01-01

    The activation of group I metabotropic glutamate receptors (mGluRs), which are coupled with Gq-protein, initiates a variety physiological responses in different types of cells. While Gq-protein-coupled receptors can upregulate N-methyl-D-aspartate (NMDA) receptor function, group I mGluR-mediated regulations of NMDA receptor function are not fully understood. To determine biochemical roles of group I mGluRs in the regulation of the NMDA receptor, we have investigated changes in tyrosine phosphorylation of NMDA receptor subunits NR2A and NR2B induced by a selective mGluR5 agonist, (RS)-chloro-5-hydroxyphenylglycine (CHPG) in hippocampal neuronal cultures. Activation of mGluR5 by CHPG increased active-forms of Src. CHPG also enhanced tyrosine phosphorylation of NR2A and NR2B in hippocampal neuronal cultures. In addition, NMDA-induced cell death was enhanced by CHPG-induced mGluR5 stimulation at the concentration, which increased tyrosine phosphorylation of Src and NR2A/2B but did not induce cell death. This effect was inhibited by selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP). The results suggest that in hippocampal neurons, mGluR5 may regulate NMDA receptor activity, involving tyrosine phosphorylation of NR2A and NR2B and may be involved in NMDA receptor-mediated cell injury.

  13. The nicotine metabolite, cotinine, attenuates glutamate (NMDA) antagonist-related effects on the performance of the five choice serial reaction time task (5C-SRTT) in rats.

    Science.gov (United States)

    Terry, Alvin V; Buccafusco, Jerry J; Schade, R Foster; Vandenhuerk, Leah; Callahan, Patrick M; Beck, Wayne D; Hutchings, Elizabeth J; Chapman, James M; Li, Pei; Bartlett, Michael G

    2012-04-01

    Cotinine, the most predominant metabolite of nicotine in mammalian species, has a pharmacological half-life that greatly exceeds its precursor. However, until recently, relatively few studies had been conducted to systematically characterize the behavioral pharmacology of cotinine. Our previous work indicated that cotinine improves prepulse inhibition of the auditory startle response in rats in pharmacological impairment models and that it improves working memory in non-human primates. Here we tested the hypothesis that cotinine improves sustained attention in rats and attenuates behavioral alterations induced by the glutamate (NMDA) antagonist MK-801. The effects of acute subcutaneous (dose range 0.03-10.0 mg/kg) and chronic oral administration (2.0 mg/kg/day in drinking water) of cotinine were evaluated in fixed and variable stimulus duration (VSD) as well as variable intertrial interval (VITI) versions of a five choice serial reaction time task (5C-SRTT). The results indicated only subtle effects of acute cotinine (administered alone) on performance of the 5C-SRTT (e.g., decreases in timeout responses). However, depending on dose, acute treatment with cotinine attenuated MK-801-related impairments in accuracy and elevations in timeout responses, and it increased the number of completed trials. Moreover, chronic cotinine attenuated MK-801-related impairments in accuracy and it reduced premature and timeout responses when the demands of the task were increased (i.e., by presenting VSDs or VITIs in addition to administering MK-801). These data suggest that cotinine may represent a prototype for compounds that have therapeutic potential for neuropsychiatric disorders (i.e., by improving sustained attention and decreasing impulsive and compulsive behaviors), especially those characterized by glutamate receptor alterations. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Synaptic NR2A- but not NR2B-containing NMDA receptors increase with blockade of ionotropic glutamate receptors

    Directory of Open Access Journals (Sweden)

    Jakob Von Engelhardt

    2009-10-01

    Full Text Available NMDA receptors are key molecules involved in physiological and pathophysiological brain processes such as plasticity and excitotoxicity. Neuronal activity regulates NMDA receptor levels in the cell membrane. However, little is known on which time scale this regulation occurs and whether the two main diheteromeric NMDA receptor subtypes in forebrain, NR1/NR2A and NR1/NR2B, are regulated in a similar fashion. As these differ considerably in their electrophysiological properties, the NR2A/NR2B ratio affects the neurons’ reaction to NMDA receptor activation. Here we provide evidence that the basal turnover rate in the cell membrane of NR2A- and NR2B-containing receptors is comparable. However, the level of the NR2A subtype in the cell membrane is highly regulated by NMDA receptor activity, resulting in a several-fold increased insertion of new receptors after blocking NMDA receptors for 8 hours. Blocking AMPA receptors also increases the delivery of NR2A-containing receptors to the cell membrane. In contrast, the amount of NR2B-containing receptors in the cell membrane is not affected by ionotropic glutamate receptor block. Moreover, electrophysiological analysis of synaptic currents in hippocampal cultures and CA1 neurons of hippocampal slices revealed that after 8 hours of NMDA receptor blockade the NMDA EPSCs increase as a result of augmented NMDA receptor-mediated currents. In conclusion, synaptic NR2A- but not NR2B-containing receptors are dynamically regulated, enabling neurons to change their NR2A/NR2B ratio within a time scale of hours.

  15. Memantine and Ketamine Differentially Alter NMDA Receptor Desensitization.

    Science.gov (United States)

    Glasgow, Nathan G; Povysheva, Nadezhda V; Azofeifa, Andrea M; Johnson, Jon W

    2017-10-04

    Memantine and ketamine are clinically useful NMDA receptor (NMDAR) open channel blockers that inhibit NMDARs with similar potency and kinetics, but display vastly different clinical profiles. This discrepancy has been hypothesized to result from inhibition by memantine and ketamine of overlapping but distinct NMDAR subpopulations. For example, memantine but not ketamine may inhibit extrasynaptic NMDARs more effectively than synaptic NMDARs. However, the basis for preferential NMDAR inhibition depending on subcellular location has not been investigated systematically. We integrated recordings from heterologously expressed single NMDAR subtypes, kinetic modeling, and recordings of synaptically evoked NMDAR responses in acute brain slices to investigate mechanisms by which channel blockers may distinguish NMDAR subpopulations. We found that memantine and ketamine differentially alter NMDAR desensitization and that memantine stabilizes a Ca 2+ -dependent desensitized state. As a result, inhibition by memantine of GluN1/2A receptors in tsA201 cells and of native synaptic NMDARs in cortical pyramidal neurons from mice of either sex increased in conditions that enhanced intracellular Ca 2+ accumulation. Therefore, differential inhibition by memantine and ketamine based on NMDAR location is likely to result from location dependence of the intensity and duration of NMDAR activation. Modulation of Ca 2+ -dependent NMDAR desensitization is an unexplored mechanism of inhibitory action with the potential to endow drugs with NMDAR selectivity that leads to superior clinical profiles. Our results suggest that designing compounds to target specific receptor states, rather than specific receptor types, may be a viable strategy for future drug development. SIGNIFICANCE STATEMENT Memantine and ketamine are NMDA receptor (NMDAR) channel-blocking drugs with divergent clinical effects. Understanding mechanistically their differential actions may advance our understanding of nervous

  16. Ionic blocking effect in partially crystallized lithium disilicate

    International Nuclear Information System (INIS)

    Campos-Junior, Alvimar A.; Rodrigues, Ana C. M.

    2006-01-01

    A lithium disilicate glass was heat treated at 454 deg. C, the temperature of maximum nucleation rate, up to 25 days. At this temperature the growth rate is negligible, and therefore these thermal treatments lead to a glassy matrix in which ellipsoidal crystals of about the same size were randomly dispersed. Crystallized volume fraction (α) of up to 20% was reached. Electrical conductivity of glassy, partially crystallized, and 100% crystallized lithium disilicate was then measured by impedance spectroscopy. The crystallized surface layer was eliminated by polishing in order to solely analyze the effect of bulk crystals. The complex plane plots of impedance data showed one or two semicircles depending on (α). The high frequency semicircle represents the vitreous matrix while the low frequency one was ascribed to the blocking effect imposed to the lithium ions by the existing crystals in the partially crystallized samples. This hypothesis was confirmed by the analysis of the relaxation frequency related to each one of the semicircles and by comparison to the relaxation frequency of lithium disilicate glass and crystal. Results show that the blocking effect produces a second semicircle in the impedance diagram starting from a crystallized volume fraction of 15%

  17. [Effects of 2000 μW/cm2; electromagnetic radiation on expression of immunoreactive protein and mRNA of NMDA receptor 2A subunit in rats hippocampus].

    Science.gov (United States)

    Li, Yu-hong; Lu, Guo-bing; Shi, Chang-hua; Zhang, Zhuo; Xu, Qian

    2011-01-01

    To evaluate the effects of electromagnetic irradiation of 2000 μW/cm(2); exposure on mRNA and protein expression levels of immunoreactive protein and mRNA of NMDA receptor 2A subunit in rats hippocampal, and to explore the mechanism of electromagnetic irradiation induced learning and memory impairment. Rats were randomly divided into normal control group, sham-radiated group, and 1 h/d, 2 h/d, and 3 h/d radiation groups. The rats in the radiation groups were fixed after microwave exposure of 2000 μW/cm(2);, then their learning and memory abilities were tested by Morris water maze experiment, the change of NR2A protein in hippocampal neurons of each group of rats were measured with immunohistochmistry and Western blot techniques, and the expression of NR2A mRNA in hippocampus were determined by RT-PCR. Compared with the normal control group, each index of the sham-radiated group has no significant change (P>0.05), while the latency of rats of radiated group in Morris water maze test were significantly longer (Pradiation group, the hippocampal neurons of rats showing evident reduction in the ratio of NR2A positive cells, irregular, and arrayed in disorder. Moreover, the expession of NR2A protein and its mRNA in hippocampal neurons were significant decreased (P<0.05). Electromagnetic irradiation of 2000 μW/cm(2); exposure can impair the learning and memory abilities of rats possibly through a mechanism correlated with the lower expression of NR2A protein and its mRNA in hippocampus.

  18. CONCRETE BLOCKS' ADVERSE EFFECTS ON INDOOR AIR AND RECOMMENDED SOLUTIONS

    Science.gov (United States)

    Air infiltration through highly permeable concrete blocks can allow entry of various serious indoor air pollutants. An easy approach to avoiding these pollutants is to select a less–air-permeable concrete block. Tests show that air permeability of concrete blocks can vary by a fa...

  19. Further insights into the anti-aggregating activity of NMDA in human platelets

    Science.gov (United States)

    Franconi, Flavia; Miceli, Mauro; Alberti, Luisa; Seghieri, Giuseppe; De Montis, M Graziella; Tagliamonte, Alessandro

    1998-01-01

    In the present study the effect of N-methyl-D-aspartate (NMDA) on thromboxane B2 synthesis and on [Ca2+]i was studied in human platelets.NMDA (10−7 M) completely inhibited the synthesis of thromboxane B2 from exogenous arachidonic acid (AA), while it did not interfere with the aggregating effect of the thromboxane A2 receptor agonist U-46619.NMDA (0.1 μM–10 μM) dose-dependently increased intracellular calcium in washed platelets pre-loaded with fura 2 AM, and this effect was not additive with that of AA.NMDA shifted the dose-response curve of AA to the right. At the highest AA concentrations platelet aggregation was not inhibited.The antiaggregating effect of NMDA was not antagonized by NG-monomethyl-L-arginine (L-NMMA), a nitric oxide synthase (NOS) inhibitor.Finally, NMDA (0.01 nM–100 nM) associated with either aspirin or indomethacin significantly potentiated the antiaggregating activity of both cyclo-oxygenase inhibitors.It was concluded that NMDA is a potent inhibitor of platelet aggregation and thromboxane B2 synthesis in human platelet rich plasma (PRP). PMID:9630340

  20. Confidence and psychosis: a neuro-computational account of contingency learning disruption by NMDA blockade.

    Science.gov (United States)

    Vinckier, F; Gaillard, R; Palminteri, S; Rigoux, L; Salvador, A; Fornito, A; Adapa, R; Krebs, M O; Pessiglione, M; Fletcher, P C

    2016-07-01

    A state of pathological uncertainty about environmental regularities might represent a key step in the pathway to psychotic illness. Early psychosis can be investigated in healthy volunteers under ketamine, an NMDA receptor antagonist. Here, we explored the effects of ketamine on contingency learning using a placebo-controlled, double-blind, crossover design. During functional magnetic resonance imaging, participants performed an instrumental learning task, in which cue-outcome contingencies were probabilistic and reversed between blocks. Bayesian model comparison indicated that in such an unstable environment, reinforcement learning parameters are downregulated depending on confidence level, an adaptive mechanism that was specifically disrupted by ketamine administration. Drug effects were underpinned by altered neural activity in a fronto-parietal network, which reflected the confidence-based shift to exploitation of learned contingencies. Our findings suggest that an early characteristic of psychosis lies in a persistent doubt that undermines the stabilization of behavioral policy resulting in a failure to exploit regularities in the environment.

  1. NMDA receptors mediate neuron-to-glia signaling in mouse cortical astrocytes.

    Science.gov (United States)

    Lalo, Ulyana; Pankratov, Yuri; Kirchhoff, Frank; North, R Alan; Verkhratsky, Alexei

    2006-03-08

    Chemical transmission between neurons and glial cells is an important element of integration in the CNS. Here, we describe currents activated by NMDA in cortical astrocytes, identified in transgenic mice that express enhanced green fluorescent protein under control of the human glial fibrillary acidic protein promoter. Astrocytes were studied by whole-cell voltage clamp either in slices or after gentle nonenzymatic mechanical dissociation. Acutely isolated astrocytes showed a three-component response to glutamate. The initial rapid component was blocked by 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX), which is an antagonist of AMPA receptors (IC50, 2 microM), and the NMDA receptor antagonist D-AP-5 blocked the later sustained component (IC50, 0.6 microM). The third component of glutamate application response was sensitive to D,L-threo-beta-benzyloxyaspartate, a glutamate transporter blocker. Fast application of NMDA evoked concentration-dependent inward currents (EC50, 0.3 microM); these showed use-dependent block by (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate (MK-801). These NMDA-evoked currents were linearly dependent on membrane potential and were not affected by extracellular magnesium at concentrations up to 10 mM. Electrical stimulation of axons in layer IV-VI induced a complex inward current in astrocytes situated in the cortical layer II, part of which was sensitive to MK-801 at holding potential -80 mV and was not affected by the AMPA glutamate receptor antagonist NBQX. The fast miniature spontaneous currents were observed in cortical astrocytes in slices as well. These currents exhibited both AMPA and NMDA receptor-mediated components. We conclude that cortical astrocytes express functional NMDA receptors that are devoid of Mg2+ block, and these receptors are involved in neuronal-glial signal transmission.

  2. Three-dimensional Reconstruction of Block Shape Irregularity and its Effects on Block Impacts Using an Energy-Based Approach

    Science.gov (United States)

    Zhang, Yulong; Liu, Zaobao; Shi, Chong; Shao, Jianfu

    2018-04-01

    This study is devoted to three-dimensional modeling of small falling rocks in block impact analysis in energy view using the particle flow method. The restitution coefficient of rockfall collision is introduced from the energy consumption mechanism to describe rockfall-impacting properties. Three-dimensional reconstruction of falling block is conducted with the help of spherical harmonic functions that have satisfactory mathematical properties such as orthogonality and rotation invariance. Numerical modeling of the block impact to the bedrock is analyzed with both the sphere-simplified model and the 3D reconstructed model. Comparisons of the obtained results suggest that the 3D reconstructed model is advantageous in considering the combination effects of rockfall velocity and rotations during colliding process. Verification of the modeling is carried out with the results obtained from other experiments. In addition, the effects of rockfall morphology, surface characteristics, velocity, and volume, colliding damping and relative angle are investigated. A three-dimensional reconstruction modulus of falling blocks is to be developed and incorporated into the rockfall simulation tools in order to extend the modeling results at block scale to slope scale.

  3. Ketamine: NMDA Receptors and Beyond

    OpenAIRE

    Zorumski, Charles F.; Izumi, Yukitoshi; Mennerick, Steven

    2016-01-01

    Human studies examining the effects of the dissociative anesthetic ketamine as a model for psychosis and as a rapidly acting antidepressant have spurred great interest in understanding ketamine's actions at molecular, cellular, and network levels. Although ketamine has unequivocal uncompetitive inhibitory effects on N-methyl-d-aspartate receptors (NMDARs) and may preferentially alter the function of NMDARs on interneurons, recent work has questioned whether block of NMDARs is critical for its...

  4. Adverse effects of iodine thyroid blocking: A systematic review

    International Nuclear Information System (INIS)

    Spallek, L.; Krille, L.; Reiners, C.; Schneider, R.; Yamashita, S.; Zeeb, H.

    2008-01-01

    131 I, when released in a radiological or nuclear accident as happened recently in Fukushima (Japan)), may cause thyroid cancer as a long-term consequence. Iodine thyroid blocking (ITB) is known to reduce the risk of developing thyroid cancer. Potential adverse effects of ITB have not been systematically investigated so far. This article summarises the results of a review on adverse effects of ITB based on a systematic literature search in scientific medical databases. A meta-analysis was not performed as identified studies displayed major heterogeneity. The search resulted in 14 articles relevant to the topic, reporting mostly on surveys, ecological and intervention studies. Only one study from Poland focused on effects (both desired and adverse) of an ITB intervention following the Chernobyl accident. All other studies reported on iodine administration in a different context. Overall, the studies did not reveal severe adverse reactions to potassium iodide in the general public. Since ITB is a protective measure only applied in very specific circumstances, scientifically sound studies of adverse effects are scarce and consequently the evidence base is weak. The assessment of adverse effects of ITB relies on indirect evidence from related areas. This study may contribute to ongoing developments in pharmaco-epidemiology aiming to better quantify adverse effects of medications and health care interventions including ITB. All rights reserved. (authors)

  5. Agmatine protects against cell damage induced by NMDA and glutamate in cultured hippocampal neurons.

    Science.gov (United States)

    Wang, Wei-Ping; Iyo, Abiye H; Miguel-Hidalgo, Javier; Regunathan, Soundar; Zhu, Meng-Yang

    2006-04-21

    Agmatine is a polyamine and has been considered as a novel neurotransmitter or neuromodulator in the central nervous system. In the present study, the neuroprotective effect of agmatine against cell damage caused by N-methyl-D-aspartate (NMDA) and glutamate was investigated in cultured rat hippocampal neurons. Lactate dehydrogenase (LDH) activity assay, beta-tubulin III immunocytochemical staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end-labeling (TUNEL) assay were conducted to detect cell damage. Exposure of 12-day neuronal cultures of rat hippocampus to NMDA or glutamate for 1 h caused a concentration-dependent neurotoxicity, as indicated by the significant increase in released LDH activities. Addition of 100 microM agmatine into media ablated the neurotoxicity induced by NMDA or glutamate, an effect also produced by the specific NMDA receptor antagonist dizocilpine hydrogen maleate (MK801). Arcaine, an analog of agmatine with similar structure as agmatine, fully prevented the NMDA- or glutamate-induced neuronal damage. Spermine and putrescine, the endogenous polyamine and metabolic products of agmatine without the guanidine moiety of agmatine, failed to show this effect, indicating a structural relevance for this neuroprotection. Immunocytochemical staining and TUNEL assay confirmed the findings in the LDH measurement. That is, agmatine and MK801 markedly attenuated NMDA-induced neuronal death and significantly reduced TUNEL-positive cell numbers induced by exposure of cultured hippocampal neurons to NMDA. Taken together, these results demonstrate that agmatine can protect cultured hippocampal neurons from NMDA- or glutamate-induced excitotoxicity, through a possible blockade of the NMDA receptor channels or a potential anti-apoptotic property.

  6. Selective vulnerabilities of N-methyl-D-aspartate (NMDA receptors during brain aging

    Directory of Open Access Journals (Sweden)

    Brenna L Brim

    2010-03-01

    Full Text Available N-methyl-D-aspartate (NMDA receptors are present in high density within the cerebral cortex and hippocampus and play an important role in learning and memory. NMDA receptors are negatively affected by aging, but these effects are not uniform in many different ways. This review discusses the selective age-related vulnerabilities of different binding sites of the NMDA receptor complex, different subunits that comprise the complex, and the expression and functions of the receptor within different brain regions. Spatial reference, passive avoidance, and working memory, as well as place field stability and expansion all involve NMDA receptors. Aged animals show deficiencies in these functions, as compared to young, and some studies have identified an association between age-associated changes in the expression of NMDA receptors and poor memory performance. A number of diet and drug interventions have shown potential for reversing or slowing the effects of aging on the NMDA receptor. On the other hand, there is mounting evidence that the NMDA receptors that remain within aged individuals are not always associated with good cognitive functioning. This may be due to a compensatory response of neurons to the decline in NMDA receptor expression or a change in the subunit composition of the remaining receptors. These studies suggest that developing treatments that are aimed at preventing or reversing the effects of aging on the NMDA receptor may aid in ameliorating the memory declines that are associated with aging. However, we need to be mindful of the possibility that there may also be negative consequences in aged individuals.

  7. Simulation study of the effect of differences in block energy and density on the self-assembly of block copolymers

    Science.gov (United States)

    Lawson, Richard A.; Peters, Andrew J.; Nation, Benjamin; Ludovice, Peter J.; Henderson, Clifford L.

    2014-03-01

    Implementation of directed self-assembly (DSA) of block copolymers (BCPs) introduces a series of engineering challenges that have not been completely addressed in previous block copolymer and lithography studies. One of the required innovations for further DSA development and implementation is the accurate simulation of specific block copolymer chemistries and their interactions with interfaces. Many of the BCP simulation tools developed so far have limitations or difficulty in terms of matching many of the common issues found in experimental BCP systems such as polydispersity and different statistical segment lengths. One of the potentially most important issues is the fact that real BCPs often have block energy and/or density asymmetry, meaning that each block has a different homopolymer density and/or cohesive energy density (CED). A simulation of BCP behavior and DSA processes based on molecular dynamics (MD) of coarse-grained polymer chains has been developed that can independently parameterize and control the density and CED of each block to more accurately match the asymmetry found in experimental BCPs. This model was used to study the effect of block asymmetry on the order-disorder transition (ODT), domain scaling, and self-assembly of thin films of BCPs. BCPs whose blocks each have a different density show deviations from the mean-field ODT coexistence curve, exhibiting an order-disorder transition or co-existence curve that is asymmetric with shifts and tilts in the direction of majority highest density block. This impact of density and cohesive energy differences diblock copolymers on their phase behavior can explain some of the unexpected shapes found experimentally in BCP ODT curves. Asymmetry in the BCP block energy or density does not appear to have a significant effect on domain scaling behavior compared to the mean-field estimates. Self-assembly of thin films of BCPs with mismatches in CED shows significant deviations in the expected morphologies

  8. Experimental Cortical Spreading Depression Induces NMDA Receptor Dependent Potassium Currents in Microglia.

    Science.gov (United States)

    Wendt, Stefan; Wogram, Emile; Korvers, Laura; Kettenmann, Helmut

    2016-06-08

    Cortical spreading depression (CSD) is a propagating event of neuronal depolarization, which is considered as the cellular correlate of the migraine aura. It is characterized by a change in the intrinsic optical signal and by a negative DC potential shift. Microglia are the resident macrophages of the CNS and act as sensors for pathological changes. In the present study, we analyzed whether microglial cells might sense CSD by recording membrane currents from microglia in acutely isolated cortical mouse brain slices during an experimentally induced CSD. Coincident with the change in the intrinsic optical signal and the negative DC potential shift we recorded an increase in potassium conductance predominantly mediated by K(+) inward rectifier (Kir)2.1, which was blocked by the NMDA receptor antagonist D-AP5. Application of NMDA and an increase in extracellular K(+) mimics the CSD-induced Kir activation. Application of D-AP5, but not the purinergic receptor antagonist RB2, blocks the NMDA-induced Kir activation. The K(+) channel blocker Ba(2+) blocks both the CSD- and the NMDA-triggered increase in Kir channel activity. In addition, we could confirm previous findings that microglia in the adult brain do not express functional NMDA receptors by recording from microglia cultured from adult brain. From these observations we conclude that CSD activates neuronal NMDA receptors, which lead to an increase in extracellular [K(+)] resulting in the activation of Kir channel activity in microglia. Cortical spreading depression (CSD) is a wave of neuronal depolarization spreading through the cortex and is associated with the aura of migraine. Here we show that microglial cells, which are viewed as pathologic sensors of the brain, can sense this wave. The increase in the extracellular potassium concentration associated with that wave leads to the activation of an inward rectifying potassium conductance in microglia. The involvement of neuronal NMDA receptors is crucial because

  9. GDNF and neublastin protect against NMDA-induced excitotoxicity in hippocampal slice cultures

    DEFF Research Database (Denmark)

    Bonde, C; Kristensen, B W; Blaabjerg, M

    2000-01-01

    The potential neuroprotective effects of glial cell line-derived neurotrophic factor (GDNF) and neublastin (NBN) against NMDA-induced excitotoxicity were examined in hippocampal brain slice cultures. Recombinant human GDNF (25-100 ng/ ml) or NBN, in medium conditioned by growth of transfected, NBN......-producing HiB5 cells, were added to slice cultures I h before exposure to 10 microM NMDA for 48h. Neuronal cell death was monitored, before and during the NMDA exposure, by densitometric measurements of propidium iodide (PI) uptake and loss of Nissl staining. Both the addition of rhGDNF and NBN...

  10. Effective dermatomal blockade after subcostal transversus abdominis plane block

    DEFF Research Database (Denmark)

    Mitchell, Anja Ulrike; Torup, Henrik; Hansen, Egon G

    2012-01-01

    . Sensory assessment of a TAP block may guide the decision on the extent of the block. The purpose of this study was to investigate if the dermatomal extent of sensory blockade after injection of 20 ml 0.5% ropivacaine bilaterally into the TAP can be assessed using cold and pinprick sensation....

  11. Effects of different building blocks designs on the statistical ...

    African Journals Online (AJOL)

    Prior to any census, the country usually gets demarcated into small geographic units called census enumeration areas, districts or blocks. In most countries, these small geographic units are also used for census dissemination. In cases where they are not used for census release, they are normally used as building blocks ...

  12. The effectiveness of pudendal nerve block versus caudal block anesthesia for hypospadias in children.

    Science.gov (United States)

    Naja, Zoher M; Ziade, Fouad M; Kamel, Raymond; El-Kayali, Sabah; Daoud, Nabil; El-Rajab, Mariam A

    2013-12-01

    Caudal block (CB) has some disadvantages, one of which is its short duration of action after a single injection. For hypospadias repair, pudendal nerve block (PNB) might be a suitable alternative since it has been successfully used for analgesia for circumcision. We evaluated PNB compared with CB as measured by total analgesic consumption 24 hours postoperatively. In this prospective, double-blinded study, patients were randomized into 2 groups, either receiving CB or nerve stimulator-guided PNB. In the PNB group, patients were injected with 0.3 mL/kg 0.25% bupivacaine and 1 µg/kg clonidine. In the CB group, patients were injected with 1 mL/kg 0.25% bupivacaine and 1 µg/kg clonidine. Analgesic consumption was assessed during the first 24 hours postoperatively. The "objective pain scale" developed by Hannalah and Broadman was used to assess postoperative pain. Eighty patients participated in the study, 40 in each group. The mean age in the PNB group was 3.1 (1.1) years and in the CB group was 3.2 (1.1) years. The mean weights in the PNB and CB groups were 15.3 (2.8) kg and 15.3 (2.2) kg, respectively. The percentage of patients who received analgesics during the first 24 hours were significantly higher in the CB (70%) compared with the PNB group (20%, P < 0.0001). The average amount of analgesics consumed per patient within 24 hours postoperatively was higher in the CB group (paracetamol P < 0.0001, Tramal P =0.003). Patients who received PNB had reduced analgesic consumption and pain within the first 24 hours postoperatively compared with CB.

  13. Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment.

    Directory of Open Access Journals (Sweden)

    Lucio A Ramos-Chávez

    2015-02-01

    Full Text Available Inorganic arsenic (iAs is an important natural pollutant. Millions of individuals worldwide drink water with high levels of iAs. Chronic exposure to iAs has been associated with lower IQ and learning disabilities as well as memory impairment. iAs is methylated in tissues such as the brain generating mono and dimethylated species. iAs methylation requires cellular glutathione (GSH, which is the main antioxidant in the central nervous system. In humans, As species cross the placenta and are found in cord blood. A CD1 mouse model was used to investigate effects of gestational iAs exposure which can lead to oxidative damage, disrupted cysteine/glutamate transport and its putative impact in learning and memory. On postnatal days (PNDs 1, 15 and 90, the expression of membrane transporters related to GSH synthesis and glutamate transport and toxicity, such as xCT, EAAC1, GLAST and GLT1, as well as LAT1, were analyzed. Also, the expression of the glutamate receptor N-methyl-D-aspartate (NMDAR subunits NR2A and B as well as the presence of As species in cortex and hippocampus were investigated. On PND 90, an object location task was performed to associate exposure with memory impairment. Gestational exposure to iAs affected the expression of cysteine/glutamate transporters in cortex and hippocampus and induced a negative modulation of NMDAR NR2B subunit in the hippocampus. Behavioral tasks showed significant spatial memory impairment in males while the effect was marginal in females.

  14. EVALUATING THE NMDA-GLUTAMATE RECEPTOR AS A SITE OF ACTION FOR TOLUENE USING PATTERN ELICITED VISUAL EVOKED POTENTIALS.

    Science.gov (United States)

    In vitro studies have demonstrated that toluene disrupts the function of NMDA-glutamate receptors, as well as other channels. This has led to the hypothesis that effects on NMDA receptor function may contribute to toluene neurotoxicity, CNS depression, and altered visual evoked ...

  15. Effects of C-phycocyanin and Spirulina on Salicylate-Induced Tinnitus, Expression of NMDA Receptor and Inflammatory Genes

    Science.gov (United States)

    Hwang, Juen-Haur; Chen, Jin-Cherng; Chan, Yin-Ching

    2013-01-01

    Effects of C-phycocyanin (C-PC), the active component of Spirulina platensis water extract on the expressions of N-methyl D-aspartate receptor subunit 2B (NR2B), tumor necrosis factor–α (TNF-α), interleukin-1β (IL-1β), and cyclooxygenase type 2 (COX-2) genes in the cochlea and inferior colliculus (IC) of mice were evaluated after tinnitus was induced by intraperitoneal injection of salicylate. The results showed that 4-day salicylate treatment (unlike 4-day saline treatment) caused a significant increase in NR2B, TNF-α, and IL-1β mRNAs expression in the cochlea and IC. On the other hand, dietary supplementation with C-PC or Spirulina platensis water extract significantly reduced the salicylate-induced tinnitus and down-regulated the mRNAs expression of NR2B, TNF-α, IL-1β mRNAs, and COX-2 genes in the cochlea and IC of mice. The changes of protein expression levels were generally correlated with those of mRNAs expression levels in the IC for above genes. PMID:23533584

  16. Role of retinal glial cell glutamate transporters in retinal ganglion cell survival following stimulation of NMDA receptor.

    Science.gov (United States)

    Furuya, Toshie; Pan, Zhiying; Kashiwagi, Kenji

    2012-03-01

    To investigate the role of glutamate transporters (GLTs)in retinal glial cells that were treated with N-methyl-D-aspartate (NMDA), in retinal ganglion cell (RGC) survival. Primary cultures of retinal glial cells or RGCs from 3-day-old Sprague-Dawley rats were employed in the present study. Retinal glial cells were treated with NMDA and changes in GLT mRNA and protein expression were analyzed. The effects of pretreating retinal glial cells with the GLAST-specific inhibitor, rottlerin (ROT), and the GLT-1-specific inhibitor, dihydrokainic acid (DHK), on RGC survival were investigated under exposure to NMDA. The amount of glutamate in the culture medium of retinal glial cells was measured by high-performance liquid chromatography. NMDA treatment increased GLAST and GLT-1 expression. GLAST and GLT-1 mRNA expression increased by 2.94-fold and 3.36-fold at 12 h after treatment with the highest concentration of NMDA (33 mM), and by 1.41-fold and 1.39-fold at 24 h, respectively. GLT-1 and GLAST protein expression also increased. MK801, an NMDA-receptor antagonist, inhibited the NMDA-induced upregulation of GLT mRNA expression. Co-culture with retinal glial cells increased the survival rate of RGCs. ROT decreased the survival rate of RGCs, whereas DHK significantly increased the survival rate of RGCs treated with 33 mM NMDA. NMDA treatment reduced the total amount of glutamate in the culture medium, particularly when 33 mM NMDA was added to the medium. ROT pretreatment increased the amount of glutamate in the culture medium, whereas DHK pretreatment decreased it. GLAST and GLT-1 may have different roles in the survival of RGCs mediated by retinal glial cells. These results suggest that the NMDA-associated induction of GLTs plays an important role in RGC survival.

  17. Synthesis of C3, C5, and C7 pregnane derivatives and their effect on NMDA receptor responses in cultured rat hippocampal neurons

    Czech Academy of Sciences Publication Activity Database

    Šťastná, Eva; Chodounská, Hana; Pouzar, Vladimír; Kapras, Vojtěch; Borovská, Jiřina; Cais, Ondřej; Vyklický ml., Ladislav

    2009-01-01

    Roč. 74, č. 2 (2009), s. 256-263 ISSN 0039-128X R&D Projects: GA ČR(CZ) GA309/07/0271; GA ČR(CZ) GA203/08/1498 Grant - others:GA MŠk(CZ) LC554; FP6 Photolysis(XE) LSHM-CT-2007-037765 Program:LC Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50110509 Keywords : pregnane derivatives * NMDA receptor * structure-activity relationship * patch- clamp recording Subject RIV: CC - Organic Chemistry Impact factor: 2.905, year: 2009

  18. Effects of Interlocking and Supporting Conditions on Concrete Block Pavements

    Science.gov (United States)

    Mahapatra, Geetimukta; Kalita, Kuldeep

    2018-02-01

    Concrete Block Paving (CBP) is widely used as wearing course in flexible pavements, preferably under light and medium vehicular loadings. Construction of CBP at site is quick and easy in quality control. Usually, flexible pavement design philosophy is followed in CBP construction, though it is structurally different in terms of small block elements with high strength concrete and their interlocking aspects, frequent joints and discontinuity, restrained edge etc. Analytical solution for such group action of concrete blocks under loading in a three dimensional multilayer structure is complex and thus, the need of conducting experimental studies is necessitated for extensive understanding of the load—deformation characteristics and behavior of concrete blocks in pavement. The present paper focuses on the experimental studies for load transfer characteristics of CBP under different interlocking and supporting conditions. It is observed that both interlocking and supporting conditions affect significantly on the load transfer behavior in CBP structures. Coro-lock block exhibits better performance in terms of load carrying capacity and distortion behavior under static loads. Plate load tests are performed over subgrade, granular sub-base (GSB), CBP with and without GSB using different block shapes. For an example case, the comparison of CBP with conventional flexible pavement section is also presented and it is found that CBP provides considerable benefit in terms of construction cost of the road structure.

  19. Protease-activated receptor 1-dependent neuronal damage involves NMDA receptor function.

    Science.gov (United States)

    Hamill, Cecily E; Mannaioni, Guido; Lyuboslavsky, Polina; Sastre, Aristide A; Traynelis, Stephen F

    2009-05-01

    Protease-activated receptor 1 (PAR1) is a G-protein coupled receptor that is expressed throughout the central nervous system. PAR1 activation by brain-derived as well as blood-derived proteases has been shown to have variable and complex effects in a variety of animal models of neuronal injury and inflammation. In this study, we have evaluated the effects of PAR1 on lesion volume in wild-type or PAR1-/- C57Bl/6 mice subjected to transient occlusion of the middle cerebral artery or injected with NMDA in the striatum. We found that removal of PAR1 reduced infarct volume following transient focal ischemia to 57% of control. Removal of PAR1 or application of a PAR1 antagonist also reduced the neuronal injury associated with intrastriatal injection of NMDA to 60% of control. To explore whether NMDA receptor potentiation by PAR1 activation contributes to the harmful effects of PAR1, we investigated the effect of NMDA receptor antagonists on the neuroprotective phenotype of PAR1-/- mice. We found that MK801 reduced penumbral but not core neuronal injury in mice subjected to transient middle cerebral artery occlusion or intrastriatal NMDA injection. Lesion volumes in both models were not significantly different between PAR1-/- mice treated with and without MK801. Use of the NMDA receptor antagonist and dissociative anesthetic ketamine also renders NMDA-induced lesion volumes identical in PAR1-/- mice and wild-type mice. These data suggest that the ability of PAR1 activation to potentiate NMDA receptor function may underlie its harmful actions during injury.

  20. Population Blocks.

    Science.gov (United States)

    Smith, Martin H.

    1992-01-01

    Describes an educational game called "Population Blocks" that is designed to illustrate the concept of exponential growth of the human population and some potential effects of overpopulation. The game material consists of wooden blocks; 18 blocks are painted green (representing land), 7 are painted blue (representing water); and the remaining…

  1. Differential antagonism of tetramethylenedisulfotetramine-induced seizures by agents acting at NMDA and GABAA receptors

    International Nuclear Information System (INIS)

    Shakarjian, Michael P.; Velíšková, Jana; Stanton, Patric K.; Velíšek, Libor

    2012-01-01

    Tetramethylenedisulfotetramine (TMDT) is a highly lethal neuroactive rodenticide responsible for many accidental and intentional poisonings in mainland China. Ease of synthesis, water solubility, potency, and difficulty to treat make TMDT a potential weapon for terrorist activity. We characterized TMDT-induced convulsions and mortality in male C57BL/6 mice. TMDT (ip) produced a continuum of twitches, clonic, and tonic–clonic seizures decreasing in onset latency and increasing in severity with increasing dose; 0.4 mg/kg was 100% lethal. The NMDA antagonist, ketamine (35 mg/kg) injected ip immediately after the first TMDT-induced seizure, did not change number of tonic–clonic seizures or lethality, but increased the number of clonic seizures. Doubling the ketamine dose decreased tonic–clonic seizures and eliminated lethality through a 60 min observation period. Treating mice with another NMDA antagonist, MK-801, 0.5 or 1 mg/kg ip, showed similar effects as low and high doses of ketamine, respectively, and prevented lethality, converting status epilepticus EEG activity to isolated interictal discharges. Treatment with these agents 15 min prior to TMDT administration did not increase their effectiveness. Post-treatment with the GABA A receptor allosteric enhancer diazepam (5 mg/kg) greatly reduced seizure manifestations and prevented lethality 60 min post-TMDT, but ictal events were evident in EEG recordings and, hours post-treatment, mice experienced status epilepticus and died. Thus, TMDT is a highly potent and lethal convulsant for which single-dose benzodiazepine treatment is inadequate in managing electrographic seizures or lethality. Repeated benzodiazepine dosing or combined application of benzodiazepines and NMDA receptor antagonists is more likely to be effective in treating TMDT poisoning. -- Highlights: ► TMDT produces convulsions and lethality at low doses in mice. ► Diazepam pre- or post-treatments inhibit TMDT-induced convulsions and death.

  2. Ketamine: NMDA Receptors and Beyond.

    Science.gov (United States)

    Zorumski, Charles F; Izumi, Yukitoshi; Mennerick, Steven

    2016-11-02

    Human studies examining the effects of the dissociative anesthetic ketamine as a model for psychosis and as a rapidly acting antidepressant have spurred great interest in understanding ketamine's actions at molecular, cellular, and network levels. Although ketamine has unequivocal uncompetitive inhibitory effects on N-methyl-d-aspartate receptors (NMDARs) and may preferentially alter the function of NMDARs on interneurons, recent work has questioned whether block of NMDARs is critical for its mood enhancing actions. In this viewpoint, we examine the evolving literature on ketamine supporting NMDARs as important triggers for certain psychiatric effects and the possibility that the antidepressant trigger is unrelated to NMDARs. The rapidly evolving story of ketamine offers great hope for untangling and treating the biology of both depressive and psychotic illnesses. Copyright © 2016 the authors 0270-6474/16/3611158-07$15.00/0.

  3. Patent Blocking and Infringement and their Effects on Firms?

    DEFF Research Database (Denmark)

    Grimpe, Christoph; Hussinger, Katrin

    In recent years, firms have increasingly contributed to and been confronted with a patent landscape characterized by numerous but marginal inventions, overlapping claims and patent fences. As a result, firms risk to be blocked in their patent applications or to be infringed upon by rivals. While ...

  4. Effects of different building blocks designs on the statistical ...

    African Journals Online (AJOL)

    Tholang T. Mokhele

    Enumeration Areas (EAs), Small Area Layers (SALs) and SubPlaces) from the 2001 census data were used as building blocks for the generation of census output areas with AZTool program in both rural and urban areas of South Africa. One way-Analysis of Variance (ANOVA) was also performed to determine statistical ...

  5. Pharmacological characterization of NMDA-like receptors in the single-celled organism Paramecium primaurelia.

    Science.gov (United States)

    Ramoino, Paola; Candiani, Simona; Pittaluga, Anna Maria; Usai, Cesare; Gallus, Lorenzo; Ferrando, Sara; Milanese, Marco; Faimali, Marco; Bonanno, Giambattista

    2014-02-01

    Paramecium primaurelia is a unicellular eukaryote that moves in freshwater by ciliary beating and responds to environmental stimuli by altering motile behaviour. The movements of the cilia are controlled by the electrical changes of the cell membrane: when the intraciliary Ca(2+) concentration associated with plasma membrane depolarization increases, the ciliary beating reverses its direction, and consequently the swimming direction changes. The ciliary reversal duration is correlated with the amount of Ca(2+) influx. Here, we evaluated the effects due to the activation or blockade of N-methyl-d-aspartic acid (NMDA) receptors on swimming behaviour in Paramecium. Paramecia normally swim forward, drawing almost linear tracks. We observed that the simultaneous administration of NMDA and glycine induced a partial ciliary reversal (PaCR) leading to a continuous spiral-like swim. Furthermore, the duration of continuous ciliary reversal (CCR), triggered by high external KCl concentrations, was longer in NMDA+glycine-treated cells. NMDA action required the presence of Ca(2+), as the normal forward swimming was restored when the ion was omitted from the extracellular milieu. The PaCR and the enhancement of CCR duration significantly decreased when the antagonists of the glutamate site D-AP5 or CGS19755, the NMDA channel blocker MK-801 or the glycine site antagonist DCKA was added. The action of NMDA+glycine was also abolished by Zn(2+) or ifenprodil, the GluN2A and the GluN2B NMDA-containing subunit blockers, respectively. Searches of the Paramecium genome database currently available indicate that the NMDA-like receptor with ligand-binding characteristics of an NMDA receptor-like complex, purified from rat brain synaptic membranes and found in some metazoan genomes, is also present in Paramecium. These results provide evidence that functional NMDA receptors similar to those typical of mammalian neuronal cells are present in the single-celled organism Paramecium and thus

  6. Hydration effects on the electronic properties of eumelanin building blocks

    International Nuclear Information System (INIS)

    Assis Oliveira, Leonardo Bruno; Fonseca, Tertius L.; Costa Cabral, Benedito J.; Coutinho, Kaline; Canuto, Sylvio

    2016-01-01

    Theoretical results for the electronic properties of eumelanin building blocks in the gas phase and water are presented. The building blocks presently investigated include the monomeric species DHI (5,6-dihydroxyindole) or hydroquinone (HQ), DHICA (5,6-dihydroxyindole-2-carboxylic acid), indolequinone (IQ), quinone methide (MQ), two covalently bonded dimers [HM ≡ HQ + MQ and IM ≡ IQ + MQ], and two tetramers [HMIM ≡ HQ + IM, IMIM ≡ IM + IM]. The electronic properties in water were determined by carrying out sequential Monte Carlo/time dependent density functional theory calculations. The results illustrate the role played by hydrogen bonding and electrostatic interactions in the electronic properties of eumelanin building blocks in a polar environment. In water, the dipole moments of monomeric species are significantly increased ([54–79]%) relative to their gas phase values. Recently, it has been proposed that the observed enhancement of the higher-energy absorption intensity in eumelanin can be explained by excitonic coupling among eumelanin protomolecules [C.-T. Chen et al., Nat. Commun. 5, 3859 (2014)]. Here, we are providing evidence that for DHICA, IQ, and HMIM, the electronic absorption toward the higher-energy end of the spectrum ([180–220] nm) is enhanced by long-range Coulombic interactions with the water environment. It was verified that by superposing the absorption spectra of different eumelanin building blocks corresponding to the monomers, dimers, and tetramers in liquid water, the behaviour of the experimental spectrum, which is characterised by a nearly monotonic decay from the ultraviolet to the infrared, is qualitatively reproduced. This result is in keeping with a “chemical disorder model,” where the broadband absorption of eumelanin pigments is determined by the superposition of the spectra associated with the monomeric and oligomeric building blocks.

  7. Hydration effects on the electronic properties of eumelanin building blocks

    Energy Technology Data Exchange (ETDEWEB)

    Assis Oliveira, Leonardo Bruno [Instituto de Física da Universidade Federal de Goiás, 74690-900 Goiânia, GO (Brazil); Departamento de Física - CEPAE, Universidade Federal de Goiás, 74690-900 Goiânia, GO (Brazil); Escola de Ciências Exatas e da Computação, Pontifícia Universidade Católica de Goiás, 74605-010 Goiânia, GO (Brazil); Fonseca, Tertius L. [Instituto de Física da Universidade Federal de Goiás, 74690-900 Goiânia, GO (Brazil); Costa Cabral, Benedito J., E-mail: ben@cii.fc.ul.pt [Grupo de Física Matemática da Universidade de Lisboa and Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa (Portugal); Coutinho, Kaline; Canuto, Sylvio [Instituto de Física da Universidade de São Paulo, CP 66318, 05314-970 São Paulo, SP (Brazil)

    2016-08-28

    Theoretical results for the electronic properties of eumelanin building blocks in the gas phase and water are presented. The building blocks presently investigated include the monomeric species DHI (5,6-dihydroxyindole) or hydroquinone (HQ), DHICA (5,6-dihydroxyindole-2-carboxylic acid), indolequinone (IQ), quinone methide (MQ), two covalently bonded dimers [HM ≡ HQ + MQ and IM ≡ IQ + MQ], and two tetramers [HMIM ≡ HQ + IM, IMIM ≡ IM + IM]. The electronic properties in water were determined by carrying out sequential Monte Carlo/time dependent density functional theory calculations. The results illustrate the role played by hydrogen bonding and electrostatic interactions in the electronic properties of eumelanin building blocks in a polar environment. In water, the dipole moments of monomeric species are significantly increased ([54–79]%) relative to their gas phase values. Recently, it has been proposed that the observed enhancement of the higher-energy absorption intensity in eumelanin can be explained by excitonic coupling among eumelanin protomolecules [C.-T. Chen et al., Nat. Commun. 5, 3859 (2014)]. Here, we are providing evidence that for DHICA, IQ, and HMIM, the electronic absorption toward the higher-energy end of the spectrum ([180–220] nm) is enhanced by long-range Coulombic interactions with the water environment. It was verified that by superposing the absorption spectra of different eumelanin building blocks corresponding to the monomers, dimers, and tetramers in liquid water, the behaviour of the experimental spectrum, which is characterised by a nearly monotonic decay from the ultraviolet to the infrared, is qualitatively reproduced. This result is in keeping with a “chemical disorder model,” where the broadband absorption of eumelanin pigments is determined by the superposition of the spectra associated with the monomeric and oligomeric building blocks.

  8. An increase in spinal dehydroepiandrosterone sulfate (DHEAS) enhances NMDA-induced pain via phosphorylation of the NR1 subunit in mice: involvement of the sigma-1 receptor.

    Science.gov (United States)

    Yoon, Seo-Yeon; Roh, Dae-Hyun; Seo, Hyoung-Sig; Kang, Suk-Yun; Moon, Ji-Young; Song, Sunok; Beitz, Alvin J; Lee, Jang-Hern

    2010-11-01

    Our laboratory has recently demonstrated that an increase in the spinal neurosteroid, dehydroepiandrosterone sulfate (DHEAS) facilitates nociception via the activation of sigma-1 receptors and/or the allosteric inhibition GABA(A) receptors. Several lines of evidence have suggested that DHEAS positively modulates N-methyl-d-aspartate (NMDA) receptor activity within the central nervous system. Moreover, we have demonstrated that the activation of sigma-1 receptors increases NMDA receptor activity. Since NMDA receptors play a key role in the enhancement of pain perception, the present study was designed to determine whether spinally administered DHEAS modulates NMDA receptor-mediated nociceptive activity and whether this effect is mediated by sigma-1 or GABA(A) receptors. Intrathecal (i.t.) DHEAS was found to significantly potentiate i.t. NMDA-induced spontaneous pain behaviors. Subsequent immunohistochemical analysis demonstrated that i.t. DHEAS also increased protein kinase C (PKC)- and protein kinase A (PKA)-dependent phosphorylation of the NMDA receptor subunit NR1 (pNR1), which was used as a marker of NMDA receptor sensitization. The sigma-1 receptor antagonist, BD-1047, but not the GABA(A) receptor agonist, muscimol, dose-dependently suppressed DHEAS's facilitatory effect on NMDA-induced nociception and pNR1 expression. In addition, pretreatment with either a PKC or PKA blocker significantly reduced the facilitatory effect of DHEAS on NMDA-induced nociception. Conversely the GABA(A) receptor antagonist, bicuculline did not affect NMDA-induced pain behavior or pNR1 expression. The results of this study suggest that the DHEAS-induced enhancement of NMDA-mediated nociception is dependent on an increase in PKC- and PKA-dependent pNR1. Moreover, this effect of DHEAS on NMDA receptor activity is mediated by the activation of spinal sigma-1 receptors and not through the inhibition of GABA(A) receptors. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. NMDA-induced accumulation of Shank at the postsynaptic density is mediated by CaMKII

    Energy Technology Data Exchange (ETDEWEB)

    Tao-Cheng, Jung-Hwa [EM Facility, NINDS, NIH, Bethesda, MD (United States); Yang, Yijung [Laboratory of Neurobiology, NINDS, NIH, Bethesda, MD (United States); Bayer, K. Ulrich [Department of Pharmacology, University of Colorado Denver, School of Medicine, Aurora, CO (United States); Reese, Thomas S. [Laboratory of Neurobiology, NINDS, NIH, Bethesda, MD (United States); Dosemeci, Ayse, E-mail: dosemeca@ninds.nih.gov [Laboratory of Neurobiology, NINDS, NIH, Bethesda, MD (United States)

    2014-07-18

    Highlights: • NMDA-induces accumulation of Shank at the postsynaptic density. • Shank accumulation is preferential to the distal region of the postsynaptic density. • Shank accumulation is mediated by CaMKII. - Abstract: Shank is a specialized scaffold protein present in high abundance at the postsynaptic density (PSD). Using pre-embedding immunogold electron microscopy on cultured hippocampal neurons, we had previously demonstrated further accumulation of Shank at the PSD under excitatory conditions. Here, using the same experimental protocol, we demonstrate that a cell permeable CaMKII inhibitor, tatCN21, blocks NMDA-induced accumulation of Shank at the PSD. Furthermore we show that NMDA application changes the distribution pattern of Shank at the PSD, promoting a 7–10 nm shift in the median distance of Shank labels away from the postsynaptic membrane. Inhibition of CaMKII with tatCN21 also blocks this shift in the distribution of Shank. Altogether these results imply that upon activation of NMDA receptors, CaMKII mediates accumulation of Shank, preferentially at the distal regions of the PSD complex extending toward the cytoplasm.

  10. The effect of salt on the morphologies of compositionally asymmetric block copolymer electrolytes

    Science.gov (United States)

    Loo, Whitney; Maslyn, Jacqueline; Oh, Hee Jeung; Balsara, Nitash

    Block copolymer electrolytes are promising for applications in lithium metal solid-state batteries. Due to their ability to microphase separate into distinct morphologies, their ion transport and mechanical properties can be decoupled. The addition of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) salt to poly(styrene)-block-poly(ethylene oxide) (SEO) has been shown to increase microphase separation in symmetric block copolymer systems due to an increase in the effective interaction parameter (χeff) ; however the effect of block copolymer compositional asymmetry is not well-understood. The effect of compositional asymmetry on polymer morphology was investigated through small and wide angle X-ray scattering (SAXS/WAXS). The effective Flory-Huggins interaction parameter was extracted from the scattering profiles in order to construct a phase diagram to demonstrate the effect of salt and compositional asymmetry on block copolymer morphology.

  11. Molecular pharmacology of human NMDA receptors

    DEFF Research Database (Denmark)

    Hedegaard, Maiken; Hansen, Kasper Bø; Andersen, Karen Toftegaard

    2012-01-01

    current knowledge of the relationship between NMDA receptor structure and function. We summarize studies on the biophysical properties of human NMDA receptors and compare these properties to those of rat orthologs. Finally, we provide a comprehensive pharmacological characterization that allows side......-by-side comparison of agonists, un-competitive antagonists, GluN2B-selective non-competitive antagonists, and GluN2C/D-selective modulators at recombinant human and rat NMDA receptors. The evaluation of biophysical properties and pharmacological probes acting at different sites on the receptor suggest...... that the binding sites and conformational changes leading to channel gating in response to agonist binding are highly conserved between human and rat NMDA receptors. In summary, the results of this study suggest that no major detectable differences exist in the pharmacological and functional properties of human...

  12. Ameliorative Effects of Neurolytic Celiac Plexus Block on Stress and ...

    African Journals Online (AJOL)

    Jun Li1, Fu-Xiang Li2, Jian-Xiang Che3, Xiao-Hong Wei4, Qing-Ming Qiu3, Peng. Zha1, Shu-Rong Bai1, Xu-Dong ..... Establishment of model treated for neurolytic celiac plexus block percutaneously with anhydrous-alcohol in rat. Chin J. Pain Med 2008; 14:233-235. 15. Wang J, Zhao J, Li J, Wang F, Su Y. Time-course.

  13. Neuromuscular NMDA Receptors Modulate Developmental Synapse Elimination.

    Science.gov (United States)

    Personius, Kirkwood E; Slusher, Barbara S; Udin, Susan B

    2016-08-24

    At birth, each mammalian skeletal muscle fiber is innervated by multiple motor neurons, but in a few weeks, all but one of those axons retracts (Redfern, 1970) and differential activity between inputs controls this phenomenon (Personius and Balice-Gordon, 2001; Sanes and Lichtman, 2001; Personius et al., 2007; Favero et al., 2012). Acetylcholine, the primary neuromuscular transmitter, has long been presumed to mediate this activity-dependent process (O'Brien et al., 1978), but glutamatergic transmission also occurs at the neuromuscular junction (Berger et al., 1995; Grozdanovic and Gossrau, 1998; Mays et al., 2009). To test the role of neuromuscular NMDA receptors, we assessed their contribution to muscle calcium fluxes in mice and tested whether they influence removal of excess innervation at the end plate. Developmental synapse pruning was slowed by reduction of NMDA receptor activation or expression and by reduction of glutamate production. Conversely, pruning is accelerated by application of exogenous NMDA. We also found that NMDA induced increased muscle calcium only during the first 2 postnatal weeks. Therefore, neuromuscular NMDA receptors play previously unsuspected roles in neuromuscular activity and synaptic pruning during development. In normal adult muscle, each muscle fiber is innervated by a single axon, but at birth, fibers are multiply innervated. Elimination of excess connections requires neural activity; because the neuromuscular junction (NMJ) is a cholinergic synapse, acetylcholine has been assumed to be the critical mediator of activity. However, glutamate receptors are also expressed at the NMJ. We found that axon removal in mice is slowed by pharmacological and molecular manipulations that decrease signaling through neuromuscular NMDA receptors, whereas application of exogenous NMDA at the NMJ accelerates synapse elimination and increases muscle calcium levels during the first 2 postnatal weeks. Therefore, neuromuscular NMDA receptors play

  14. Involvement of NMDA glutamate receptors in the acquisition and reinstatement of the conditioned place preference induced by MDMA.

    Science.gov (United States)

    García-Pardo, Maria P; Escobar-Valero, Carla; Rodríguez-Arias, Marta; Miñarro, Jose; Aguilar, Maria A

    2015-08-01

    Some 3,4-methylenedioxymethamphetamine (MDMA) users become dependent as a result of chronic consumption. A greater understanding of the neurobiological basis of the rewarding effects of MDMA could contribute to developing effective pharmacotherapies for MDMA-related problems. The present study evaluated the role of N-methyl-D-aspartate (NMDA) glutamate receptors (NMDARs) in the acquisition and reinstatement of conditioned place preference (CPP) induced by MDMA. Adolescent male mice were conditioned with 1 or 10 mg/kg MDMA and pretreated with 5 or 10 mg/kg of the NMDAR antagonist memantine during acquisition of conditioning (experiment 1), or before a reinstatement test (experiment 2). In addition, the effects of memantine on acquisition of chocolate-induced CPP and the effects of memantine and MDMA on a passive avoidance task were evaluated. Memantine did not exert any motivational effects, but blocked the acquisition of MDMA-induced CPP. Moreover, following acquisition and extinction of MDMA-induced CPP, memantine did not induce reinstatement but blocked reinstatement of the CPP induced by priming with MDMA. Memantine did not block the CPP induced by chocolate, and it partially reversed the impairing effects of MDMA on memory. Our results demonstrate that NMDARs are involved in acquisition of the conditioned rewarding effects of MDMA and in priming-induced reinstatement of CPP following extinction. Moreover, they suggest the validity of memantine for the treatment of MDMA abuse.

  15. Effect of concrete block weight and wall height on electromyographic activity and heart rate of masons.

    Science.gov (United States)

    Anton, D; Rosecrance, J C; Gerr, F; Merlino, L A; Cook, T M

    2005-08-15

    Work-related musculoskeletal disorders (MSDs) are common among construction workers, such as masons. Few interventions are available to reduce masons' exposure to heavy lifting, a risk factor for MSDs. The purpose of this study was to determine whether one such intervention, the use of light-weight concrete blocks (LWBs), reduces physiological loads compared to standard-weight blocks (SWBs). Using a repeated measures design, 21 masons each constructed two 32-block walls, seven courses (rows) high, entirely of either SWBs or LWBs. Surface electromyography (EMG), from arm and back muscles, and heart rate was sampled. For certain muscles, EMG amplitudes were slightly lower when masons were laying LWBs compared to SWBs. Upper back and forearm extensor EMG amplitudes were greater for the higher wall courses for both block weights. There were no significant differences in heart rate between the two blocks. Interventions that address block weight and course height may be effective for masons.

  16. Increased NMDA receptor inhibition at an increased Sevoflurane MAC

    Directory of Open Access Journals (Sweden)

    Brosnan Robert J

    2012-06-01

    Full Text Available Abstract Background Sevoflurane potently enhances glycine receptor currents and more modestly decreases NMDA receptor currents, each of which may contribute to immobility. This modest NMDA receptor antagonism by sevoflurane at a minimum alveolar concentration (MAC could be reciprocally related to large potentiation of other inhibitory ion channels. If so, then reduced glycine receptor potency should increase NMDA receptor antagonism by sevoflurane at MAC. Methods Indwelling lumbar subarachnoid catheters were surgically placed in 14 anesthetized rats. Rats were anesthetized with sevoflurane the next day, and a pre-infusion sevoflurane MAC was measured in duplicate using a tail clamp method. Artificial CSF (aCSF containing either 0 or 4 mg/mL strychnine was then infused intrathecally at 4 μL/min, and the post-infusion baseline sevoflurane MAC was measured. Finally, aCSF containing strychnine (either 0 or 4 mg/mL plus 0.4 mg/mL dizocilpine (MK-801 was administered intrathecally at 4 μL/min, and the post-dizocilpine sevoflurane MAC was measured. Results Pre-infusion sevoflurane MAC was 2.26%. Intrathecal aCSF alone did not affect MAC, but intrathecal strychnine significantly increased sevoflurane requirement. Addition of dizocilpine significantly decreased MAC in all rats, but this decrease was two times larger in rats without intrathecal strychnine compared to rats with intrathecal strychnine, a statistically significant (P  Conclusions Glycine receptor antagonism increases NMDA receptor antagonism by sevoflurane at MAC. The magnitude of anesthetic effects on a given ion channel may therefore depend on the magnitude of its effects on other receptors that modulate neuronal excitability.

  17. Evaluation of the Interaction between NMDA Receptors of Nucleus Accumbens and Muscarinic Receptors in Memory

    Directory of Open Access Journals (Sweden)

    Saba Taheri

    2013-02-01

    Full Text Available Background and Objectives: Whereas studies have indicated the interaction between NMDA and cholinergic systems, this study was performed with the aim of determining the role of NMDA receptors in the nucleus accumbens (NAc in scopolamine-induced amnesia.Methods: In this study, at first rats were anesthetized with intra-peritoneal injection of ketamine hydrochloride plus xylazine, and then placed in a stereotaxic apparatus. Two stainless-steel cannulas were placed 2mm above nucleus accumbens shell. All animals were allowed to recover for one week, before beginning the behavioral testing. Then, animals were trained in a step-through type inhibitory avoidance task. The drugs were injected after successful training and before testing. The animals were tested 24h after training, and the step-through latency time was measured as the memory criterion in male Wistar rats. One-way analysis of variance and Tukey’s test were used for analysis of the data. p<0.05 was considered statistically significant.Results: Intra-nucleus accumbens (intra-NAc injection of scopolamine or NMDA caused impairment in memory in rats. Although, co-administration of an ineffective dose of NMDA with an ineffective dose of scopolamine had no significant effect on memory performance, effective doses of NMDA prevented the amnesic effect of scopolamine on inhibitory avoidance memory. On the other hand, intra-NAc injection of NMDA receptor antagonist, i.e., MK-801 caused no change in memory performance by itself, and its co-administration with an effective dose of scopolamine could not prevent the impairing effect of the latter drug. Conclusion: The finding of this study indicated that NMDA receptors in the nucleus accumbens are involved in the modulation of scopolamine-induced amnesia.

  18. Effect of a Wide Stance on Block Start Performance in Sprint Running.

    Science.gov (United States)

    Otsuka, Mitsuo; Kurihara, Toshiyuki; Isaka, Tadao

    2015-01-01

    This study aimed to clarify the effect of widened stance width at the set position during the block start phase in sprint running on kinematics and kinetics at the hip joint and block-induced power. Fourteen male sprinters volunteered to participate in this study. They performed three block-start trials with a normal stance width (25 ± 1 cm, normal condition) and a widened stance width (45 ± 2 cm, widened condition) at the set position. The block start movements were recorded at 250 Hz with high-speed cameras and the ground reaction forces at 1250 Hz with force plates. During the block phase in the widened condition, the hip abduction and external rotation angles in both legs were significantly larger and smaller, respectively, than those in the normal condition. The positive peak value of the hip power in the rear leg was significantly greater in the widened condition than that in the normal condition. However, no significant difference was seen in the normalized block-induced power between the widened and normal conditions. We conclude that a widened stance width at the set position affects the hip-joint kinematics and rear hip power generation during the block start phase, but no effect on the block-induced power when considering sprinting performance during the whole block start phase.

  19. Evaluation of effects of sciatic and femoral nerve blocks in sheep undergoing stifle surgery.

    Science.gov (United States)

    Wagner, Ann E; Mama, Khursheed R; Ruehlman, Dana L; Pelkey, Sheila; Turner, A Simon

    2011-04-01

    The authors evaluated the effects of locally anesthetizing the sciatic and femoral nerves in sheep undergoing stifle (femorotibial) surgery (16 sheep received nerve blocks; 16 sheep underwent a nerve localization procedure but received no nerve blocks). Heart rate, mean arterial blood pressure and end-tidal isoflurane were recorded every 5 min while sheep were anesthetized. At some of the observed time points, the mean heart rate in the sheep that had received no nerve blocks was significantly higher than in the sheep that had received the nerve blocks. Postoperatively, each sheep was assigned scores for comfort and attitude, movement, flock behavior, feeding behavior and appetite and respiratory rate (based on predefined descriptions). Though the authors found no undesirable effects of this local anesthesia, beneficial effects of the nerve blocks were minimal or not readily apparent under the conditions of this study.

  20. The elusive nature of the blocking effect : 15 failures to replicate

    NARCIS (Netherlands)

    Maes, E.; Boddez, Y.; Alfei, J.M.; Krypotos, A.-M.; D'Hooge, R.; De Houwer, J.; Beckers, T.

    2016-01-01

    With the discovery of the blocking effect, learning theory took a huge leap forward, because blocking provided a crucial clue that surprise is what drives learning. This in turn stimulated the development of novel association-formation theories of learning. Eventually, the ability to explain

  1. Diurnal inhibition of NMDA-EPSCs at rat hippocampal mossy fibre synapses through orexin-2 receptors

    Science.gov (United States)

    Perin, Martina; Longordo, Fabio; Massonnet, Christine; Welker, Egbert; Lüthi, Anita

    2014-01-01

    Diurnal release of the orexin neuropeptides orexin-A (Ox-A, hypocretin-1) and orexin-B (Ox-B, hypocretin-2) stabilises arousal, regulates energy homeostasis and contributes to cognition and learning. However, whether cellular correlates of brain plasticity are regulated through orexins, and whether they do so in a time-of-day-dependent manner, has never been assessed. Immunohistochemically we found sparse but widespread innervation of hippocampal subfields through Ox-A- and Ox-B-containing fibres in young adult rats. The actions of Ox-A were studied on NMDA receptor (NMDAR)-mediated excitatory synaptic transmission in acute hippocampal slices prepared around the trough (Zeitgeber time (ZT) 4–8, corresponding to 4–8 h into the resting phase) and peak (ZT 23) of intracerebroventricular orexin levels. At ZT 4–8, exogenous Ox-A (100 nm in bath) inhibited NMDA receptor-mediated excitatory postsynaptic currents (NMDA-EPSCs) at mossy fibre (MF)–CA3 (to 55.6 ± 6.8% of control, P = 0.0003) and at Schaffer collateral–CA1 synapses (70.8 ± 6.3%, P = 0.013), whereas it remained ineffective at non-MF excitatory synapses in CA3. Ox-A actions were mediated postsynaptically and blocked by the orexin-2 receptor (OX2R) antagonist JNJ10397049 (1 μm), but not by orexin-1 receptor inhibition (SB334867, 1 μm) or by adrenergic and cholinergic antagonists. At ZT 23, inhibitory effects of exogenous Ox-A were absent (97.6 ± 2.9%, P = 0.42), but reinstated (87.2 ± 3.3%, P = 0.002) when endogenous orexin signalling was attenuated for 5 h through i.p. injections of almorexant (100 mg kg−1), a dual orexin receptor antagonist. In conclusion, endogenous orexins modulate hippocampal NMDAR function in a time-of-day-dependent manner, suggesting that they may influence cellular plasticity and consequent variations in memory performance across the sleep–wake cycle. PMID:25085886

  2. Carrying-over effects of GVBD blocking on post-blocking meiotic progression of oocytes: species difference and the signaling pathway leading to MPF activation.

    Directory of Open Access Journals (Sweden)

    Guang-Zhong Jiao

    Full Text Available Efforts to improve the quality of in vitro matured oocytes by blocking germinal vesicle breakdown (GVBD and allowing more time for ooplasmic maturation have achieved little due to a lack of knowledge on the molecular events during GVBD blocking. Such knowledge is also important for studies aimed at regulating gene expression in maturing oocytes prior to GVBD. We studied species difference and signaling pathways leading to the carrying-over effect of GVBD blocking on post-blocking meiotic progression (PBMP. Overall, GVBD-blocking with roscovitine decelerated PBMP of mouse oocytes but accelerated that of pig oocytes. During blocking culture, whereas cyclin B of pig oocytes increased continuously, that of mouse oocytes declined first and then increased slowly. In both species, (a whereas active CDC2A showed a dynamics similar to cyclin B, inactive CDC2A decreased continuously; (b when oocytes were blocked in blocking medium containing cycloheximide, PBMP was decelerated significantly while cyclin B and active CDC2A decreasing to the lowest level; (c whereas sodium vanadate in blocking medium reduced PBMP, epidermal growth factor (EGF in blocking medium accelerated PBMP significantly with no effect on cyclin B levels. In conclusion, the EGF signaling cascade accelerated PBMP by promoting the pre-MPF (M-phase-promoting factor to MPF conversion during GVBD blocking with roscovitine. The significant difference in PBMP observed between mouse and pig oocytes was caused by species difference in cyclin B dynamics during blocking culture as no species difference was observed in either pre-MPF to MPF conversion or the EGF signaling activity.

  3. [Quadratus lumborum block: are we aware of its side effects? A report of 2 cases].

    Science.gov (United States)

    Sá, Miguel; Cardoso, José Miguel; Reis, Hugo; Esteves, Marta; Sampaio, José; Gouveia, Isabel; Carballada, Pilar; Pinheiro, Célia; Machado, Duarte

    2017-05-23

    The quadratus lumborum block was initially described in 2007 and aims at blocking the same nerves as the ones involved on the Transverse Abdominis Plane block, while accomplishing some visceral enervation as well due to closer proximity with the neuroaxis and sympathetic trunk. Given its versatility, we have successfully used it in a wide range of procedures. We report two cases where we believe the dispersion of local anesthetic is likely to have led to a previously undescribed complication. We report two cases in which we performed a quadratus lumborum type II block and general anesthesia for total gastrectomy and right hemicolectomy. There were no noteworthy events while performing the block and inducing general anesthesia, but within 30-40min serious hypotension and tachycardia were noted. As other motives for hypotension were ruled out, the event was interpreted as block-induced sympatholysis due to cephalad dispersion of the local anesthetic to the paravertebral and epidural space, and successfully managed with ephedrine and increase of the crystalloid infusion rate. The quadratus Lumborum block is safe to execute and provides effective abdominal wall and visceral analgesia. However, the possibility of eliciting undesired episodes should prompt caution when performing this block and practitioners should thereafter remain vigilant. Questions regarding ideal dosing, volumes, timing of block and pertinence of catheters remain to be answered. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  4. Effects of Morphology on Dynamics of Block Copolymer Systems

    Science.gov (United States)

    Shen, Kuan-Hsuan; Hall, Lisa

    It is well known that block copolymers can microphase separate into ordered structures such as lamellae, hexagonally packed cylinders, or the bicontinuous double gyroid phase. Understanding the dynamics of the chains themselves and of added selective small molecule penetrants is relevant to the design of polymeric systems for transport applications. We expect that chain and penetrant dynamics are strongly dependent on morphology, while chain dynamics are also significantly impacted by individual polymer conformations within the morphology. For instance, in prior work on tapered polymers with a midblock of various concentration profiles, chains that fold back and forth across the lamellar interface were shown to have significantly decreased diffusion. Here we use coarse-grained molecular dynamics simulations to study how chain and penetrant dynamics depend on domain spacing, polymer conformations, and microphase morphology. We initialize systems of various fractions of A monomers in lamellar, cylinder, or gyroid microphases by growing polymers in a constrained random walk such that the two blocks are placed on opposite sides of the interface. We include, for comparison, systems with the same fraction of A that are initialized (and kinetically trapped) in different microphases, and show how this impacts polymer relaxation. How the dependence of penetrant diffusion on morphology relates to that of polymer chains will also be discussed. This material is based upon work supported by the National Science Foundation under Grant 1454343.

  5. DOSE-RESPONSE RELATION, NEUROMUSCULAR BLOCKING ACTION, INTUBATION CONDITIONS, AND CARDIOVASCULAR EFFECTS OF ORG-9273, A NEW NEUROMUSCULAR BLOCKING-AGENT

    NARCIS (Netherlands)

    VANDENBROEK, L; LAMBALK, LM; RICHARDSON, FJ; WIERDA, JMKH

    The ED50 and the ED90, the time-course of the neuromuscular block, the intubation conditions, and the cardiovascular effects of Org 9273, a new steroidal nondepolarizing neuromuscular blocking agent, have been evaluated in 41 anesthetized patients. From cumulative dose-response curves the ED50 and

  6. Block Play and Mathematics Learning in Preschool: The Effects of Building Complexity, Peer and Teacher Interactions in the Block Area, and Replica Play Materials

    Science.gov (United States)

    Trawick-Smith, Jeffrey; Swaminathan, Sudha; Baton, Brooke; Danieluk, Courtney; Marsh, Samantha; Szarwacki, Monika

    2017-01-01

    Block play has been included in early childhood classrooms for over a century, yet few studies have examined its effects on learning. Several previous investigations indicate that the complexity of block building is associated with math ability, but these studies were often conducted in adult-guided, laboratory settings. In the present…

  7. N-Methyl-d-Aspartate (NMDA) Receptor Blockade Prevents Neuronal Death Induced by Zika Virus Infection.

    Science.gov (United States)

    Costa, Vivian V; Del Sarto, Juliana L; Rocha, Rebeca F; Silva, Flavia R; Doria, Juliana G; Olmo, Isabella G; Marques, Rafael E; Queiroz-Junior, Celso M; Foureaux, Giselle; Araújo, Julia Maria S; Cramer, Allysson; Real, Ana Luíza C V; Ribeiro, Lucas S; Sardi, Silvia I; Ferreira, Anderson J; Machado, Fabiana S; de Oliveira, Antônio C; Teixeira, Antônio L; Nakaya, Helder I; Souza, Danielle G; Ribeiro, Fabiola M; Teixeira, Mauro M

    2017-04-25

    Zika virus (ZIKV) infection is a global health emergency that causes significant neurodegeneration. Neurodegenerative processes may be exacerbated by N -methyl-d-aspartate receptor (NMDAR)-dependent neuronal excitoxicity. Here, we have exploited the hypothesis that ZIKV-induced neurodegeneration can be rescued by blocking NMDA overstimulation with memantine. Our results show that ZIKV actively replicates in primary neurons and that virus replication is directly associated with massive neuronal cell death. Interestingly, treatment with memantine or other NMDAR blockers, including dizocilpine (MK-801), agmatine sulfate, or ifenprodil, prevents neuronal death without interfering with the ability of ZIKV to replicate in these cells. Moreover, in vivo experiments demonstrate that therapeutic memantine treatment prevents the increase of intraocular pressure (IOP) induced by infection and massively reduces neurodegeneration and microgliosis in the brain of infected mice. Our results indicate that the blockade of NMDARs by memantine provides potent neuroprotective effects against ZIKV-induced neuronal damage, suggesting it could be a viable treatment for patients at risk for ZIKV infection-induced neurodegeneration. IMPORTANCE Zika virus (ZIKV) infection is a global health emergency associated with serious neurological complications, including microcephaly and Guillain-Barré syndrome. Infection of experimental animals with ZIKV causes significant neuronal damage and microgliosis. Treatment with drugs that block NMDARs prevented neuronal damage both in vitro and in vivo These results suggest that overactivation of NMDARs contributes significantly to the neuronal damage induced by ZIKV infection, and this is amenable to inhibition by drug treatment. Copyright © 2017 Costa et al.

  8. Contribution of the basolateral amygdala NMDA and muscarinic receptors in rat's memory retrieval.

    Science.gov (United States)

    Nazarinia, Efat; Rezayof, Ameneh; Sardari, Maryam; Yazdanbakhsh, Nima

    2017-03-01

    The present study was designed to investigate the involvement of the muscarinic cholinergic receptors in the basolateral amygdala (BLA) in memory retrieval. Also, the possible relationship between the BLA muscarinic cholinergic and the NMDA receptor systems was evaluated in the inhibitory avoidance learning. Male Wistar rats were bilaterally cannulated into the BLAs and memory retrieval was measured in a step-through type inhibitory avoidance apparatus. Intra-BLA microinjection of different doses of a non-selective muscarinic receptor antagonist, scopolamine (0.5-1μg/rat, intra-BLA), 5min before the testing phase dose-dependently induced amnesia. Pre-test intra-BLA microinjection of different doses of NMDA (0.005-0.05μg/rat) reversed scopolamine-induced amnesia and improved memory retrieval. In addition, different doses of a selective NMDA receptor antagonist, D-AP5 (0.001-0.005μg/rat, intra-BLA) potentiated the response of an ineffective dose of scopolamine (0.5μg/rat) to inhibit memory retrieval. It should be considered that pre-test intra-BLA microinjection of the same doses of NMDA or D-AP5 by themselves had no effect on memory retrieval. Similar to ANOVA analysis, our cubic interpolation analysis also predicted that the activation or inactivation of the NMDA receptors by different doses of drugs can affect the scopolamine response. On the other hand, pre-test intra-BLA microinjection of D-AP5 inhibited the reversal effect of NMDA on scopolamine-induced amnesia. It can be concluded that the BLA cholinergic system, via muscarinic receptors, has a critical role in memory retrieval. Our results also suggest that a cooperative interaction between the BLA NMDA and muscarinic acetylcholine receptors modulates memory formation of inhibitory avoidance task in rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Effect of filter vent blocking on carbon monoxide exposure from selected lower tar cigarette brands.

    Science.gov (United States)

    Sweeney, C T; Kozlowski, L T; Parsa, P

    1999-05-01

    Two studies were conducted to determine the effect of blocking filter vents on carbon monoxide (CO) exposure under ad lib smoking conditions. In Study 1, 12 daily cigarette smokers smoked cigarettes from the brands Now (1 mg tar by the FTC Method) and Marlboro Lights (10 mg tar) under each of two vent-blocking conditions (unblocked and finger blocked). Blocking filter vents with fingers led to an 85% increase in CO for the brand Now, but had no added effect on CO exposure from the Marlboro Lights. In Study 2, another 12 daily cigarette smokers smoked cigarettes from each of four additional brands: Carlton (1 mg tar), Now (2 mg tar), Virginia Slims Ultra-lights (5 mg tar), and Virginia Slims Lights (8 mg tar). Blocking filter vents with the lips caused all four brands to produce equal CO exposures. Blocking vents increased smokers' exposure to CO by 239% when smoking Carltons and by 44% when smoking Nows. No significant increases in CO with blocking were found for either of the Virginia Slims brands. These results suggest that the degree to which a brand is ventilated determines whether that brand is susceptible to increased CO yields as a result of vent blocking.

  10. Switching of N-Methyl-d-aspartate (NMDA) Receptor-favorite Intracellular Signal Pathways from ERK1/2 Protein to p38 Mitogen-activated Protein Kinase Leads to Developmental Changes in NMDA Neurotoxicity*

    Science.gov (United States)

    Xiao, Lin; Hu, Chun; Feng, Chunzhi; Chen, Yizhang

    2011-01-01

    Excitotoxicity mediated by overactivation of N-methyl-d-aspartate receptors (NMDARs) has been implicated in a variety of neuropathological conditions in the central nervous system (CNS). It has been suggested that N-methyl-d-aspartate (NMDA) neurotoxicity is developmentally regulated, but the definite pattern of the regulation has been controversial, and the underlying mechanism remains largely unknown. Here, we show that NMDA treatment leads to significant cell death in mature (9 and 12 days in vitro) hippocampal neurons or hippocampi of young postnatal day 12 and adult rats but not in immature (3 and 6 days in vitro) neurons or embryonic day 18 and neonatal rat hippocampi. In contrast, NMDA promotes survival of immature neurons against tropic deprivation. Interestingly, it is found that NMDA preferentially activates p38 MAPK in mature neuron and adult rat hippocampus, but it favors ERK1/2 activation in immature neuron and postnatal day 0 rat hippocampus. Moreover, it is shown that NMDA neurotoxicity in mature neuron is mediated via p38 MAPK activation, and neuroprotection in immature neuron is mediated via ERK1/2 activation, whereas all these effects are NR2B-containing NMDAR-dependent, as well as Ca2+-dependent. We also revealed that mature and immature neurons showed no difference in the amplitude of NMDA-induced intracellular calcium ([Ca2+]i) increase. However, the basal level of [Ca2+]i is shown to elevate with the maturation of neuron, and this elevation is attributable to the changes in NMDA neurotoxicity but not to the switch of the NMDAR signaling pathway. Taken together, our results suggest that a switch of NMDA receptor-favorite intracellular signal pathways from ERK1/2 to p38 MAPK and the elevated basal level of [Ca2+]i with age might be critical for the developmental changes in NMDA neurotoxicity in the hippocampal neuron. PMID:21474451

  11. Switching of N-methyl-D-aspartate (NMDA) receptor-favorite intracellular signal pathways from ERK1/2 protein to p38 mitogen-activated protein kinase leads to developmental changes in NMDA neurotoxicity.

    Science.gov (United States)

    Xiao, Lin; Hu, Chun; Feng, Chunzhi; Chen, Yizhang

    2011-06-10

    Excitotoxicity mediated by overactivation of N-methyl-D-aspartate receptors (NMDARs) has been implicated in a variety of neuropathological conditions in the central nervous system (CNS). It has been suggested that N-methyl-D-aspartate (NMDA) neurotoxicity is developmentally regulated, but the definite pattern of the regulation has been controversial, and the underlying mechanism remains largely unknown. Here, we show that NMDA treatment leads to significant cell death in mature (9 and 12 days in vitro) hippocampal neurons or hippocampi of young postnatal day 12 and adult rats but not in immature (3 and 6 days in vitro) neurons or embryonic day 18 and neonatal rat hippocampi. In contrast, NMDA promotes survival of immature neurons against tropic deprivation. Interestingly, it is found that NMDA preferentially activates p38 MAPK in mature neuron and adult rat hippocampus, but it favors ERK1/2 activation in immature neuron and postnatal day 0 rat hippocampus. Moreover, it is shown that NMDA neurotoxicity in mature neuron is mediated via p38 MAPK activation, and neuroprotection in immature neuron is mediated via ERK1/2 activation, whereas all these effects are NR2B-containing NMDAR-dependent, as well as Ca(2+)-dependent. We also revealed that mature and immature neurons showed no difference in the amplitude of NMDA-induced intracellular calcium ([Ca(2+)](i)) increase. However, the basal level of [Ca(2+)](i) is shown to elevate with the maturation of neuron, and this elevation is attributable to the changes in NMDA neurotoxicity but not to the switch of the NMDAR signaling pathway. Taken together, our results suggest that a switch of NMDA receptor-favorite intracellular signal pathways from ERK1/2 to p38 MAPK and the elevated basal level of [Ca(2+)](i) with age might be critical for the developmental changes in NMDA neurotoxicity in the hippocampal neuron.

  12. NMDA antagonist, but not nNOS inhibitor, requires AMPA receptors in the ventromedial prefrontal cortex (vmPFC) to induce antidepressant-like effects

    DEFF Research Database (Denmark)

    Pereira, V. S.; Wegener, Gregers; Joca, S. R.

    2013-01-01

    Depressed individuals and stressed animals show enhanced levels of glutamate and neuronal nitric oxide synthase (nNOS) activity in limbic structures, including the vmPFC. Systemic administration of glutamatergic NMDA receptor antagonists or inhibitors of nitric oxide (NO) synthesis induces...... of the glutamatergic and nitrergic systems of the vmPFC on the behavioral consequences induced by forced swimming (FS), an animal model of depression. Male Wistar rats (230-260g) with guide cannulas aimed at the prelimbic (PL) region of vmPFC were submitted to a 15min session of FS and, 24h later, they were submitted...... administration into vmPFC-PL reduced the IT (Mean(plus or minus)SEM: vehicle: 116.3(plus or minus)21.17; LY 1nmol: 164.4(plus or minus)18.92; LY 3nmol: 28.71(plus or minus)10.21null; LY 10nmol: 39.43(plus or minus)7.99null; nullp...

  13. Kilohertz Electrical Stimulation Nerve Conduction Block: Effects of Electrode Surface Area.

    Science.gov (United States)

    Patel, Yogi A; Kim, Brian S; Rountree, William S; Butera, Robert J

    2017-10-01

    Kilohertz electrical stimulation (KES) induces repeatable and reversible conduction block of nerve activity and is a potential therapeutic option for various diseases and disorders resulting from pathological or undesired neurological activity. However, successful translation of KES nerve block to clinical applications is stymied by many unknowns, such as the relevance of the onset response, acceptable levels of waveform contamination, and optimal electrode characteristics. We investigated the role of electrode geometric surface area on the KES nerve block threshold using 20- and 40-kHz current-controlled sinusoidal KES. Electrodes were electrochemically characterized and used to characterize typical KES waveforms and electrode charge characteristics. KES nerve block amplitudes, onset duration, and recovery of normal conduction after delivery of the KES were evaluated along with power requirements for effective KES nerve block. Results from this investigation demonstrate that increasing electrode geometric surface area provides for a more power-efficient KES nerve block. Reductions in block threshold by increased electrode surface area were found to be KES-frequency-dependent, with block thresholds and average power consumption reduced by greater than two times with 20-kHz KES waveforms and greater than three times for 40-kHz KES waveforms.

  14. Adenosine A1 receptor activation modulates N-methyl-d-aspartate (NMDA) preconditioning phenotype in the brain.

    Science.gov (United States)

    Constantino, Leandra C; Pamplona, Fabrício A; Matheus, Filipe C; Ludka, Fabiana K; Gomez-Soler, Maricel; Ciruela, Francisco; Boeck, Carina R; Prediger, Rui D; Tasca, Carla I

    2015-04-01

    N-methyl-d-aspartate (NMDA) preconditioning is induced by subtoxic doses of NMDA and it promotes a transient state of resistance against subsequent lethal insults. Interestingly, this mechanism of neuroprotection depends on adenosine A1 receptors (A1R), since blockade of A1R precludes this phenomenon. In this study we evaluated the consequences of NMDA preconditioning on the hippocampal A1R biology (i.e. expression, binding properties and functionality). Accordingly, we measured A1R expression in NMDA preconditioned mice (75mg/kg, i.p.; 24h) and showed that neither the total amount of receptor, nor the A1R levels in the synaptic fraction was altered. In addition, the A1R binding affinity to the antagonist [(3)H] DPCPX was slightly increased in total membrane extracts of hippocampus from preconditioned mice. Next, we evaluated the impact of NMDA preconditioning on A1R functioning by measuring the A1R-mediated regulation of glutamate uptake into hippocampal slices and on behavioral responses in the open field and hot plate tests. NMDA preconditioning increased glutamate uptake into hippocampal slices without altering the expression of glutamate transporter GLT-1. Interestingly, NMDA preconditioning also induced antinociception in the hot plate test and both effects were reversed by post-activation of A1R with the agonist CCPA (0.2mg/kg, i.p.). NMDA preconditioning or A1R modulation did not alter locomotor activity in the open field. Overall, the results described herein provide new evidence that post-activation of A1R modulates NMDA preconditioning-mediated responses, pointing to the importance of the cross-talk between glutamatergic and adenosinergic systems to neuroprotection. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Neuregulin and BDNF induce a switch to NMDA receptor-dependent myelination by oligodendrocytes.

    Science.gov (United States)

    Lundgaard, Iben; Luzhynskaya, Aryna; Stockley, John H; Wang, Zhen; Evans, Kimberley A; Swire, Matthew; Volbracht, Katrin; Gautier, Hélène O B; Franklin, Robin J M; Attwell, David; Káradóttir, Ragnhildur T

    2013-12-01

    Myelination is essential for rapid impulse conduction in the CNS, but what determines whether an individual axon becomes myelinated remains unknown. Here we show, using a myelinating coculture system, that there are two distinct modes of myelination, one that is independent of neuronal activity and glutamate release and another that depends on neuronal action potentials releasing glutamate to activate NMDA receptors on oligodendrocyte lineage cells. Neuregulin switches oligodendrocytes from the activity-independent to the activity-dependent mode of myelination by increasing NMDA receptor currents in oligodendrocyte lineage cells 6-fold. With neuregulin present myelination is accelerated and increased, and NMDA receptor block reduces myelination to far below its level without neuregulin. Thus, a neuregulin-controlled switch enhances the myelination of active axons. In vivo, we demonstrate that remyelination after white matter damage is NMDA receptor-dependent. These data resolve controversies over the signalling regulating myelination and suggest novel roles for neuregulin in schizophrenia and in remyelination after white matter damage.

  16. Effects of blocking farm mink's feed access with open water

    Directory of Open Access Journals (Sweden)

    C.P.B HANSEN

    2008-12-01

    Full Text Available Thirty-eight farm mink were used to investigate whether open water in some instances could be a barrier to farm mink. Half of the animals grew up with free access to swimming water in a basin, the other half to an empty middle cage. Access between the cage containing the nest box and the cage containing the feed was either through the basin/middle cage or through a tunnel above it. Twenty-four hours before observations, the animals were confined without feed to the cage containing the nest box. Observations were carried out over two and a half hours after re-opening one of the access routes to the feed. When access was through the water filled basin, the animals were slower in reaching the feed and crossed between the feed and the nest box fewer times compared to both the same animals using the tunnel and the animals having a dry middle cage. In addition, animals scratched more at the blocked tunnel access when the available route was through the water than when it was through the dry middle cage. The results led to the conclusion that, under some circumstances, water can act as a barrier when farm minks are approaching feed. This indicates that water for swimming is not necessarily an environmental enrichment for, and that the lack of it would not impair the welfare of ranch mink.;

  17. Effect of Preoperative Pain on Inferior Alveolar Nerve Block

    Science.gov (United States)

    Aggarwal, Vivek; Singla, Mamta; Subbiya, Arunajatesan; Vivekanandhan, Paramasivam; Sharma, Vikram; Sharma, Ritu; Prakash, Venkatachalam; Geethapriya, Nagarajan

    2015-01-01

    The present study tested the hypothesis that the amount and severity of preoperative pain will affect the anesthetic efficacy of inferior alveolar nerve block (IANB) in patients with symptomatic irreversible pulpitis. One-hundred seventy-seven adult volunteer subjects, actively experiencing pain in a mandibular molar, participated in this prospective double-blind study carried out at 2 different centers. The patients were classified into 3 groups on the basis of severity of preoperative pain: mild, 1–54 mm on the Heft-Parker visual analog scale (HP VAS); moderate, 55–114 mm; and severe, greater than 114 mm. After IANB with 1.8 mL of 2% lidocaine, endodontic access preparation was initiated. Pain during treatment was recorded using the HP VAS. The primary outcome measure was the ability to undertake pulp access and canal instrumentation with no or mild pain. The success rates were statistically analyzed by multiple logistic regression test. There was a significant difference between the mild and severe preoperative pain group (P = .03). There was a positive correlation between the values of preoperative and intraoperative pain (r = .2 and .4 at 2 centers). The amount of preoperative pain can affect the anesthetic success rates of IANB in patients with symptomatic irreversible pulpitis. PMID:26650491

  18. 5-Hydroxytryptamine type 7 receptor neuroprotection against NMDA-induced excitotoxicity is PDGFβ receptor dependent.

    Science.gov (United States)

    Vasefi, Maryam S; Kruk, Jeff S; Heikkila, John J; Beazely, Michael A

    2013-04-01

    The serotonin (5-HT) type 7 receptor is expressed throughout the CNS including the hippocampus. Long-term (2-24 h) activation of 5-HT7 receptors regulates growth factor receptor expression, including the expression of platelet-derived growth factor (PDGF) β receptors. Direct activation of PDGFβ receptors in primary hippocampal and cortical neurons inhibits NMDA receptor activity and attenuates NMDA receptor-induced neurotoxicity. Our objective was to investigate whether the 5-HT7 receptor-induced increase in PDGFβ receptor expression would be similarly neuroprotective. We demonstrate that 5-HT7 receptor agonist treatment in primary hippocampal neurons also increases the expression of phospholipase C (PLC) γ, a downstream effector of PDGFβ receptors associated with the inhibition of NMDA receptor activity. To determine if the up-regulation of PDGFβ receptors is neuroprotective, primary hippocampal neurons were incubated with the 5-HT7 receptor agonist, LP 12, for 24 h. Indeed, LP 12 treatment prevented NMDA-induced neurotoxicity and this effect was dependent on PDGFβ receptor kinase activity. Treatment of primary neurons with LP 12 also differentially altered NMDA receptor subunit expression, reducing the expression of NR1 and NR2B, but not NR2A. These findings demonstrate the potential for providing growth factor receptor-dependent neuroprotective effects using small-molecule ligands of G protein-coupled receptors. © 2013 International Society for Neurochemistry.

  19. Kindling-induced potentiation of excitatory and inhibitory inputs to hippocampal dentate granule cells. II. Effects of the NMDA antagonist MK-801.

    LENUS (Irish Health Repository)

    Robinson, G B

    1991-10-18

    The effect of the non-competitive N-methyl-D-aspartate antagonist MK-801 on the early development of kindling-induced potentiation was examined in the rabbit hippocampal dentate gyrus. MK-801 (0.5 mg\\/kg) was administered 2 h before each daily kindling stimulation was applied to the perforant path. This treatment continued for the first 10 days of kindling. MK-801 depressed the growth of the afterdischarge duration and suppressed development of behavioral seizures. MK-801 did not block kindling-induced potentiation of either the perforant path-dentate granule cell population spike or excitatory postsynaptic potential. Random impulse train stimulation and non-linear systems analytic techniques were used to examine kindling-induced potentiation of presumed GABAergic recurrent inhibitory circuits. Both the magnitude and duration of kindling-induced response inhibition, to the second of each pair of impulses within the train, were reduced in rabbits pretreated with MK-801. These results suggest that MK-801 differentially affects kindling-induced potentiation of excitatory and inhibitory circuits within the rabbit hippocampal dentate gyrus.

  20. A Posterior TAP Block Provides More Effective Analgesia Than a Lateral TAP Block in Patients Undergoing Laparoscopic Gynecologic Surgery: A Retrospective Study.

    Science.gov (United States)

    Yoshiyama, Sakatoshi; Ueshima, Hironobu; Sakai, Ryomi; Otake, Hiroshi

    2016-01-01

    Background. There are a few papers that compared the lateral transversus abdominis plane (TAP) block with the posterior TAP block. Our study aimed to compare retrospectively the quality of analgesia after laparoscopic gynecologic surgery using the lateral TAP block with general anesthesia versus the posterior TAP block with general anesthesia. Method. Sixty-seven adult female patients were included in this retrospective study. Of these patients, thirty-four patients received the lateral TAP block with general anesthesia (lat. TAP group), and the rest of thirty-three patients received the posterior TAP block with general anesthesia (pos. TAP group). Pain scores both at rest and at movement and the use of additional analgesic drugs were recorded in the postoperative care unit within twenty-four hours after the operation. Postoperative complications were noted. Results. Patients who received pos. TAP reported lower visual analog scale (VAS) pain scores in all points, within twenty-four hours after the operation, than patients who received lat. TAP. Moreover, with the use of additional analgesic drugs, the incidence of nausea and vomiting during the first twenty-four hours after surgery was lower in the pos. TAP group than in the lat. TAP group. Conclusion. The posterior TAP block provided more effective analgesia than the lateral TAP block in patients undergoing laparoscopic gynecologic surgery.

  1. COMPARISON OF THE EFFECTIVENESS OF RADICULAR BLOCKING TECHNIQUES IN THE TREATMENT OF LUMBAR DISK HERNIA

    Directory of Open Access Journals (Sweden)

    Igor de Barcellos Zanon

    2015-12-01

    Full Text Available Objective : Compare the interlaminar blocking technique with the transforaminal blocking, with regard to pain and the presence or absence of complications. Methods : Prospective, descriptive and comparative, double-blind, randomized study, with 40 patients of both sex suffering from sciatic pain due to central-lateral or foraminal disc herniation, who did not respond to 20 physiotherapy sessions and had no instability diagnosed on examination of dynamic radiography. The type of blocking, transforaminal or interlaminar, to be performed was determined by draw. Results : We evaluated 40 patients, 17 males, mean age 49 years, average VAS pre-blocking of 8.85, average values in transforaminal technique in 24 hours, 7, 21, and 90 days of 0.71, 1.04, 2.33 and 3.84, respectively; the average VAS post-blocking for interlaminar technique was 0.89, 1.52, 3.63 and 4.88. The techniques differ only in the post-blocking period of 21 days and overall post-blocking, with significance of p=0.022 and p=0.027, respectively. Conclusion : Both techniques are effective in relieving pain and present low complication rate, and the transforaminal technique proved to be the most effective.

  2. NMDA receptor activity in neuropsychiatric disorders

    Directory of Open Access Journals (Sweden)

    Shaheen E Lakhan

    2013-06-01

    Full Text Available N-Methyl-D-aspartate (NMDA receptors play a variety of physiologic roles and their proper signaling is essential for cellular homeostasis. Any disruption in this pathway, leading to either enhanced or decreased activity, may result in the manifestation of neuropsychiatric pathologies such as schizophrenia, mood disorders, substance induced psychosis, Huntington's disease, Alzheimer's disease, and neuropsychiatric systemic lupus erythematosus. Here, we explore the notion that the overlap in activity of at least one biochemical pathway, the NMDA receptor pathway, may be the link to understanding the overlap in psychotic symptoms between diseases. This review intends to present a broad overview of those neuropsychiatric disorders for which alternations in NMDA receptor activity is prominent thus suggesting that continued direction of pharmaceutical intervention to this pathway may present a viable option for managing symptoms.

  3. Blocked natural ventilation: the effect of a source mass flux

    Science.gov (United States)

    Woods, Andrew W.; Caulfield, C. P.; Phillips, Jeremy C.

    2003-11-01

    We analyse the density evolution of fluid within a confined ventilated space resulting from the action of a dense turbulent plume originating at the top of the space with finite source volume flux, Q_0, and initial source buoyancy flux, B_0. The space is ventilated through upper and lower openings of areas A_u and A_l respectively, which are separated by a vertical distance H. We show that if Q_0(3 {<} ) 2 B_0 H c_l(2) A_l(2) (where c_l is an empirically determined discharge coefficient) then a two-layer steady stratification becomes established in the room, with outflow through the lower opening and inflow through the upper opening. The interface location depends not only on the geometry of the openings, but also the source conditions. We show that as Q_0 increases for fixed B_0, the height of the interface, which equals the depth of the lower layer of relatively dense fluid, increases. Eventually, when the source volume flux has a value greater than Q_m {=} (c_l A_l)(2/3) (2B_0 H)(1/3) , the natural exchange flow becomes blocked and a steady outflow through both of the openings develops. As a result, the density of the fluid throughout the room gradually evolves towards the density of the incoming dense fluid. We compare our theoretical predictions with a series of laboratory experiments, and discuss the implications of our model for the design of ventilation systems.

  4. Effect of hexane on magnetic blocking behavior of FePt nanoparticles

    Science.gov (United States)

    Şimşek, Telem; Akansel, Serkan; Özcan, Şadan

    2012-11-01

    In this work effect of the carrier fluid, hexane, on the magnetic properties of 4.7 nm sized FePt nanoparticles is investigated. Nanoparticles are synthesized by chemical method. Structural and magnetic characterizations confirmed that samples are monodispersed with disordered face centered cubic (fcc) crystal structure and, magnetically, exhibit two blocking behaviors; the first is at 27 K and second at 110 K. Carrier fluid of particles, hexane, is found to influence the blocking of 7% of the total magnetic moments in the system by freezing at low temperatures resulting in a two blocking phenomena even for nanoparticles that are monodispersed with narrow particle size distribution.

  5. Effects of Interscalene Nerve Block for Postoperative Pain Management in Patients after Shoulder Surgery.

    Science.gov (United States)

    Chen, Hsiu-Pin; Shen, Shih-Jyun; Tsai, Hsin-I; Kao, Sheng-Chin; Yu, Huang-Ping

    2015-01-01

    Shoulder surgery can produce severe postoperative pain and movement limitations. Evidence has shown that regional nerve block is an effective management for postoperative shoulder pain. The purpose of this study was to investigate the postoperative analgesic effect of intravenous patient-controlled analgesia (PCA) combined with interscalene nerve block in comparison to PCA alone after shoulder surgery. In this study, 103 patients receiving PCA combined with interscalene nerve block (PCAIB) and 48 patients receiving PCA alone after shoulder surgery were included. Patients' characteristics, preoperative shoulder score and range of motion, surgical and anesthetic condition in addition to visual analog scale (VAS) pain score, postoperative PCA consumption, and adverse outcomes were evaluated. The results showed that PCA combined with interscalene nerve block (PCAIB) group required less volume of analgesics than PCA alone group in 24 hours (57.76 ± 23.29 mL versus 87.29 ± 33.73 mL, p shoulder surgery.

  6. Blockade of NMDA receptors prevents analgesic tolerance to repeated transcutaneous electrical nerve stimulation (TENS) in rats

    Science.gov (United States)

    Hingne, Priyanka M.; Sluka, Kathleen A.

    2008-01-01

    Repeated daily application transcutaneous electrical nerve stimulation (TENS) results in tolerance, at spinal opioid receptors, to the anti-hyperalgesia produced by TENS. Since N-Methyl-D-Aspartate (NMDA) receptor antagonists prevent analgesic tolerance to opioid agonists we hypothesized that blockade of NMDA receptors will prevent tolerance to TENS. In rats with knee joint inflammation, TENS was applied for 20 minute daily at high frequency (100 Hz), low frequency (4 Hz), or sham TENS. Rats were treated with the NMDA antagonist MK-801 (0.01 mg/kg-0.1 mg/kg) or vehicle daily before TENS. Paw withdrawal thresholds were tested before and after inflammation, and before and after TENS treatment for 4 days. On day 1 TENS reversed the decreased mechanical withdrawal threshold induced by joint inflammation. On day 4 TENS had no effect on the decreased withdrawal threshold in the group treated with vehicle demonstrating development of tolerance. However, in the group treated with 0.1 mg/kg MK-801, TENS significantly reversed the mechanical withdrawal thresholds on day 4 demonstrating that tolerance did not develop. Vehicle treated animals developed cross-tolerance at spinal opioid receptors. Treatment with MK-801 reversed this cross-tolerance at spinal opioid receptors. In summary, blockade of NMDA receptors prevents analgesic tolerance to daily TENS by preventing tolerance at spinal opioid receptors. Perspective Tolerance observed to the clinical treatment of TENS could be prevented by administration of pharmaceutical agents with NMDA receptors activity such as ketamine or dextromethorphan. PMID:18061543

  7. NMDA modulates oligodendrocyte differentiation of subventricular zone cells through PKC activation

    Directory of Open Access Journals (Sweden)

    Fabio eCavaliere

    2013-12-01

    Full Text Available Multipotent cells from the juvenile subventricular zone (SVZ possess the ability to differentiate into new neural cells. Depending on local signals, SVZ can generate new neurons, astrocytes or oligodendrocytes. We previously demonstrated that activation of NMDA receptors in SVZ progenitors increases the rate of oligodendrocyte differentiation. Here we investigated the mechanisms involved in NMDA receptor-dependent differentiation. Using functional studies performed with the reporter gene luciferase we found that activation of NMDA receptor stimulates PKC. In turn, stimulation of PKC precedes the activation of NADPH oxidase (NOX as demonstrated by translocation of the p67phox subunit to the cellular membrane. We propose that NOX2 is involved in the transduction of the signal from NMDA receptors through PKC activation as the inhibitor gp91 reduced their pro-differentiation effect. In addition, our data and that from other groups suggest that signaling through the NMDA receptor/PKC/NOX2 cascade generates ROS that activate the PI3/mTOR pathway and finally leads to the generation of new oligodendrocytes.

  8. Mechanistic insights into xenon inhibition of NMDA receptors from MD simulations.

    Science.gov (United States)

    Liu, Lu Tian; Xu, Yan; Tang, Pei

    2010-07-15

    Inhibition of N-methyl-D-aspartate (NMDA) receptors has been viewed as a primary cause of xenon anesthesia, yet the mechanism is unclear. Here, we investigated interactions between xenon and the ligand-binding domain (LBD) of a NMDA receptor and examined xenon-induced structural and dynamical changes that are relevant to functional changes of the NMDA receptor. Several comparative molecular dynamics simulations were performed on two X-ray structures representing the open- and closed-cleft LBD of the NMDA receptor. We identified plausible xenon action sites in the LBD, including those nearby agonist sites, in the hinge region, and at the interface between two subunits. The xenon-binding energy varies from -5.3 to -0.7 kcal/mol. Xenon's effect on the NMDA receptor is conformation-dependent and is produced through both competitive and noncompetitive mechanisms. Xenon can promote cleft opening in the absence of agonists and consequently stabilizes the closed channel. Xenon can also bind at the interface of two subunits, alter the intersubunit interaction, and lead to a reduction of the distance between two GT linkers. This reduction corresponds to a rearrangement of the channel toward a direction of pore size decreasing, implying a closed or desensitized channel. In addition to these noncompetitive actions, xenon was found to weaken the glutamate binding, which could lead to low agonist efficacy and appear as competitive inhibition.

  9. N-methyl-D-aspartate (NMDA) impairs myogenesis in C2C12 cells.

    Science.gov (United States)

    Auh, Q-SChick; Park, Kyung-Ran; Lee, Myeong-Ok; Hwang, Mi-Jin; Kang, Soo-Kyung; Hong, Jung-Pyo; Yun, Hyung-Mun; Kim, Eun-Cheol

    2017-09-01

    N-methyl-d-aspartate (NMDA) is expressed in sensory neurons and plays important roles in peripheral pain mechanisms. The aim of this study was to examine the effects and molecular mechanisms of NMDA on C2C12 myoblast proliferation and differentiation. Cytotoxicity and differentiation were examined by the MTT assay, reverse transcription-polymerase chain reaction, and immunofluorescence. NMDA had no cytotoxicity (10-500 μM) and inhibited myoblastic differentiation of C2C12 cells, as assessed by F-actin immunofluorescence and levels of mRNAs encoding myogenic markers such as myogenin and myosin heavy-chain 2. It inhibited phosphorylation of mammalian target of rapamycin (mTOR) by inactivating mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38. It induced reactive oxygen species production. Furthermore, NMDA-suppressed expression of F-actin was reversed by adding the antioxidant N-acetylcysteine. Collectively, these results indicate that NMDA impairs myogenesis or myogenic differentiation in C2C12 cells through the mTOR/MAPK signaling pathways and may lead to skeletal muscle degeneration. Muscle Nerve 56: 510-518, 2017. © 2016 Wiley Periodicals, Inc.

  10. The beneficial effect of transversus abdominis plane block after laparoscopic cholecystectomy in day-case surgery

    DEFF Research Database (Denmark)

    Petersen, Pernille Lykke; Stjernholm, Pia; Kristiansen, Viggo B

    2012-01-01

    Laparoscopic cholecystectomy is associated with postoperative pain of moderate intensity in the early postoperative period. Recent randomized trials have demonstrated the efficacy of transversus abdominis plane (TAP) block in providing postoperative analgesia after abdominal surgery. We hypothesi...... hypothesized that a TAP block may reduce pain while coughing and at rest for the first 24 postoperative hours, opioid consumption, and opioid side effects in patients undergoing laparoscopic cholecystectomy in day-case surgery....

  11. Fast, non-competitive and reversible inhibition of NMDA-activated currents by 2-BFI confers neuroprotection.

    Directory of Open Access Journals (Sweden)

    Zhao Han

    Full Text Available Excessive activation of the N-methyl-D-aspartic acid (NMDA type glutamate receptors (NMDARs causes excitotoxicity, a process important in stroke-induced neuronal death. Drugs that inhibit NMDA receptor-mediated [Ca(2+]i influx are potential leads for development to treat excitotoxicity-induced brain damage. Our previous studies showed that 2-(2-benzofu-ranyl-2-imidazoline (2-BFI, an immidazoline receptor ligand, dose-dependently protects rodent brains from cerebral ischemia injury. However, the molecular mechanisms remain unclear. In this study, we found that 2-BFI transiently and reversibly inhibits NMDA, but not AMPA currents, in a dose-dependent manner in cultured rat cortical neurons. The mechanism of 2-BFI inhibition of NMDAR is through a noncompetitive fashion with a faster on (Kon = 2.19±0.33×10(-9 M(-1 sec(-1 and off rate (Koff = 0.67±0.02 sec(-1 than those of memantine, a gold standard for therapeutic inhibition NMDAR-induced excitotoxicity. 2-BFI also transiently and reversibly blocked NMDA receptor-mediated calcium entry to cultured neurons and provided long-term neuroprotection against NMDA toxicity in vitro. Collectively, these studies demonstrated a potential mechanism of 2-BFI-mediated neuroprotection and indicated that 2-BFI is an excellent candidate for repositioning as a drug for stroke treatment.

  12. CENTRAL REINFORCING EFFECTS OF ETHANOL ARE BLOCKED BY CATALASE INHIBITION

    OpenAIRE

    Nizhnikov, Michael Edward; Molina, Juan Carlos; Spear, Norman

    2007-01-01

    Recent studies have systematically indicated that newborn rats are highly sensitive to ethanol’s positive reinforcing effects. Central administrations of ethanol (25–200 mg %) associated with an olfactory conditioned stimulus (CS) promote subsequent conditioned approach to the CS as evaluated through the newborn’s response to a surrogate nipple scented with the CS. It has been shown that ethanol’s first metabolite, acetaldehyde, exerts significant reinforcing effects in the central nervous sy...

  13. Social memory in mice: disruption with an NMDA antagonist and attenuation with antipsychotic drugs.

    Science.gov (United States)

    Gao, Xue-Min; Elmer, Gregory I; Adams-Huet, Beverley; Tamminga, Carol A

    2009-04-01

    Social recognition reflects the ability of one animal to learn and remember the identity of another. Animal models of social learning and memory are pertinent to several different CNS diseases involving disruptions in cognition. Moreover, the increased understanding of the basic biology of memory increases the likelihood of discovery of memory-enhancing treatments in these human diseases. In the present study, we investigated the effects of the non-competitive NMDA antagonist ketamine on social recognition in mice across a broad dose range (5-30 mg/kg) and time-course (60 min-7 days). We also tested the ability of two antipsychotic drugs, haloperidol and olanzapine, to block the ketamine effect. Our results show that mice demonstrate social recognition over a several day period, with loss of recognition between 3-7 days. Ketamine disrupts social memory at doses which do not affect task performance. Chronic oral administration of haloperidol or olanzapine attenuates these ketamine-induced effects on social recognition, tending to normalize the memory behavior. The neural mechanisms of these actions are not known, although medial temporal lobe memory systems have been implicated.

  14. Enhanced NMDA receptor-mediated modulation of excitatory neurotransmission in the dorsal vagal complex of streptozotocin-treated, chronically hyperglycemic mice.

    Science.gov (United States)

    Bach, Eva C; Halmos, Katalin Cs; Smith, Bret N

    2015-01-01

    A variety of metabolic disorders, including complications experienced by diabetic patients, have been linked to altered neural activity in the dorsal vagal complex. This study tested the hypothesis that augmentation of N-Methyl-D-Aspartate (NMDA) receptor-mediated responses in the vagal complex contributes to increased glutamate release in the dorsal motor nucleus of the vagus nerve (DMV) in mice with streptozotocin-induced chronic hyperglycemia (i.e., hyperglycemic mice), a model of type 1 diabetes. Antagonism of NMDA receptors with AP-5 (100 μM) suppressed sEPSC frequency in vagal motor neurons recorded in vitro, confirming that constitutively active NMDA receptors regulate glutamate release in the DMV. There was a greater relative effect of NMDA receptor antagonism in hyperglycemic mice, suggesting that augmented NMDA effects occur in neurons presynaptic to the DMV. Effects of NMDA receptor blockade on mEPSC frequency were equivalent in control and diabetic mice, suggesting that differential effects on glutamate release were due to altered NMDA function in the soma-dendritic membrane of intact afferent neurons. Application of NMDA (300 μM) resulted in greater inward current and current density in NTS neurons recorded from hyperglycemic than control mice, particularly in glutamatergic NTS neurons identified by single-cell RT-PCR for VGLUT2. Overall expression of NR1 protein and message in the dorsal vagal complex were not different between the two groups. Enhanced postsynaptic NMDA responsiveness of glutamatergic NTS neurons is consistent with tonically-increased glutamate release in the DMV in mice with chronic hyperglycemia. Functional augmentation of NMDA-mediated responses may serve as a physiological counter-regulatory mechanism to control pathological disturbances of homeostatic autonomic function in type 1 diabetes.

  15. Reactivity effect of poisoned beryllium block shuffling in the MARIA reactor

    International Nuclear Information System (INIS)

    Andrzejewski, K.; Kulikowska, T.

    2000-01-01

    The paper is a continuation of the analysis of beryllium blocks poisoning by Li-6 and He-3 in the MARIA reactor, presented at the 22 RERTR Meeting in Budapest. A new computational tool, the REBUS-3 code, has been used for predicting the amount of poison. The code has been put into operation on a HP computer and the beryllium transmutation chains have been activated with assistance of the ANL RERTR staff. The horizontal and vertical poison distribution within beryllium blocks has been studied. A simple shuffling of beryllium blocks has been simulated to check the effect of exchanging a block with high poison concentration, adjacent to fuel elements, with a peripheral one with a low poison concentration

  16. Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation through activating the NR2B subunits of NMDA receptors

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Wen-Zhu [Anesthesia and Operation Center, Hainan Branch of Chinese PLA General Hospital, Hainan 572013 (China); Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853 (China); Miao, Yu-Liang [Department of Anesthesiology, PLA No. 306 Hospital, Beijing 100101 (China); Guo, Wen-Zhi [Department of Anesthesiology, Beijing Military General Hospital of Chinese People’s Liberation Army, Beijing 100700 (China); Wu, Wei, E-mail: wwzwgk@163.com [Department of Head and Neck Surgery of Otolaryngology, PLA No. 306 Hospital, Beijing 100101 (China); Li, Bao-Wei [Department of Head and Neck Surgery of Otolaryngology, PLA No. 306 Hospital, Beijing 100101 (China); An, Li-Na [Department of Anesthesiology, Armed Police General Hospital, Beijing 100039 (China); Fang, Wei-Wu [Department of Anesthesiology, PLA No. 306 Hospital, Beijing 100101 (China); Mi, Wei-Dong, E-mail: elite2005gg@163.com [Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853 (China)

    2014-04-25

    Highlights: • Leptin promotes the proliferation of neural stem cells isolated from embryonic mouse hippocampus. • Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation. • The effects of leptin are partially mediated by upregulating NR2B subunits. - Abstract: Corticosterone inhibits the proliferation of hippocampal neural stem cells (NSCs). The removal of corticosterone-induced inhibition of NSCs proliferation has been reported to contribute to neural regeneration. Leptin has been shown to regulate brain development, improve angiogenesis, and promote neural regeneration; however, its effects on corticosterone-induced inhibition of NSCs proliferation remain unclear. Here we reported that leptin significantly promoted the proliferation of hippocampal NSCs in a concentration-dependent pattern. Also, leptin efficiently reversed the inhibition of NSCs proliferation induced by corticosterone. Interestingly, pre-treatment with non-specific NMDA antagonist MK-801, specific NR2B antagonist Ro 25-6981, or small interfering RNA (siRNA) targeting NR2B, significantly blocked the effect of leptin on corticosterone-induced inhibition of NSCs proliferation. Furthermore, corticosterone significantly reduced the protein expression of NR2B, whereas pre-treatment with leptin greatly reversed the attenuation of NR2B expression caused by corticosterone in cultured hippocampal NSCs. Our findings demonstrate that leptin reverses the corticosterone-induced inhibition of NSCs proliferation. This process is, at least partially mediated by increased expression of NR2B subunits of NMDA receptors.

  17. Central reinforcing effects of ethanol are blocked by catalase inhibition.

    Science.gov (United States)

    Nizhnikov, Michael E; Molina, Juan C; Spear, Norman E

    2007-11-01

    Recent studies have systematically indicated that newborn rats are highly sensitive to ethanol's positive reinforcing effects. Central administrations of ethanol (25-200mg %) associated with an olfactory conditioned stimulus (CS) promote subsequent conditioned approach to the CS as evaluated through the newborn's response to a surrogate nipple scented with the CS. It has been shown that ethanol's first metabolite, acetaldehyde, exerts significant reinforcing effects in the central nervous system. A significant amount of acetaldehyde is derived from ethanol metabolism via the catalase system. In newborn rats, catalase levels are particularly high in several brain structures. The present study tested the effect of catalase inhibition on central ethanol reinforcement. In the first experiment, pups experienced lemon odor either paired or unpaired with intracisternal (IC) administrations of 100mg% ethanol. Half of the animals corresponding to each learning condition were pretreated with IC administrations of either physiological saline or a catalase inhibitor (sodium-azide). Catalase inhibition completely suppressed ethanol reinforcement in paired groups without affecting responsiveness to the CS during conditioning or responding by unpaired control groups. A second experiment tested whether these effects were specific to ethanol reinforcement or due instead to general impairment in learning and expression capabilities. Central administration of an endogenous kappa opioid receptor agonist (dynorphin A-13) was used as an alternative source of reinforcement. Inhibition of the catalase system had no effect on the reinforcing properties of dynorphin. The present results support the hypothesis that ethanol metabolism regulated by the catalase system plays a critical role in determination of ethanol reinforcement in newborn rats.

  18. Subunit Arrangement and Function in NMDA Receptors

    Energy Technology Data Exchange (ETDEWEB)

    Furukawa,H.; Singh, S.; Mancusso, R.; Gouaux, E.

    2005-01-01

    Excitatory neurotransmission mediated by NMDA (N-methyl-D-aspartate) receptors is fundamental to the physiology of the mammalian central nervous system. These receptors are heteromeric ion channels that for activation require binding of glycine and glutamate to the NR1 and NR2 subunits, respectively. NMDA receptor function is characterized by slow channel opening and deactivation, and the resulting influx of cations initiates signal transduction cascades that are crucial to higher functions including learning and memory. Here we report crystal structures of the ligand-binding core of NR2A with glutamate and that of the NR1-NR2A heterodimer with glutamate and glycine. The NR2A-glutamate complex defines the determinants of glutamate and NMDA recognition, and the NR1-NR2A heterodimer suggests a mechanism for ligand-induced ion channel opening. Analysis of the heterodimer interface, together with biochemical and electrophysiological experiments, confirms that the NR1-NR2A heterodimer is the functional unit in tetrameric NMDA receptors and that tyrosine 535 of NR1, located in the subunit interface, modulates the rate of ion channel deactivation.

  19. Anti-NMDA Receptor Encephalitis and Vaccination.

    Science.gov (United States)

    Wang, Hsiuying

    2017-01-18

    Anti- N -methyl-d-aspartate (Anti-NMDA) receptor encephalitis is an acute autoimmune neurological disorder. The cause of this disease is often unknown, and previous studies revealed that it might be caused by a virus, vaccine or tumor. It occurs more often in females than in males. Several cases were reported to be related to vaccination such as the H1N1 vaccine and tetanus/diphtheria/pertussis and polio vaccines. In this study, we reported an anti-NMDA receptor encephalitis case that may be caused by Japanese encephalitis vaccination. To investigate the association between anti-NMDA receptor encephalitis and vaccination, we analyzed the phylogenetic relationship of the microRNAs, which significantly regulate these vaccine viruses or bacteria, and the phylogenetic relationship of these viruses and bacteria. This reveals that anti-NMDA receptor encephalitis may be caused by Japanese encephalitis vaccination, as well as H1N1 vaccination or tetanus/diphtheria/pertussis and polio vaccinations, from the phylogenetic viewpoint.

  20. The influence of Pauli blocking effects on the properties of dense hydrogen

    International Nuclear Information System (INIS)

    Ebeling, W; Blaschke, D; Redmer, R; Reinholz, H; Roepke, G

    2009-01-01

    We investigate the effects of Pauli blocking on the properties of hydrogen at high pressures, where recent experiments have shown a transition from insulating behavior to metal-like conductivity. Since the Pauli principle prevents multiple occupation of electron states (Pauli blocking), atomic states disintegrate subsequently at high densities (Mott effect). We calculate the energy shifts due to Pauli blocking and discuss the Mott effect solving an effective Schroedinger equation for strongly correlated systems. The ionization equilibrium is treated on the basis of a chemical approach. Results for the ionization equilibrium and the pressure in the region 4000 K < T < 20 000 K are presented. We show that the transition to a highly conducting state is softer than found in earlier work. A first-order phase transition is observed at T < 6450 K, but a diffuse transition appears still up to 20 000 K

  1. Evaluation of the radial effective conductivity for VHTR standard fuel block

    International Nuclear Information System (INIS)

    Cho, Bong Hyun; Noh, Jae Man

    2012-01-01

    GAMMA+ code solves the temperature field of the solid part and fluid part independently, by modeling the reactor core as porous media. And then, it solves two temperature fields of solid parts which are divided as 1 D fueled zone and multi D un fueled zone, simultaneously. In this code, a radial effective conductivity is used for simplicity in calculating unfueled zone, where this value is expressed as the sum of the conduction through the helium coolant and graphite moderator, and the cavity radiation heat transfer between coolant flow path and fuel block. Actually, GAMMA+ uses the value of the radial effective conductivity which is obtained through the correlations generalized by the void fraction. In order to obtain the most accurate value for radial effective conductivity, the full modeling of the actual fuel block would be needed. In this paper, CFD code, Fluent is applied to predict the accurate radial effective conductivity for a standard fuel block of VHTR reactor

  2. Novel Fluorine-Containing NMDA Antagonists for Brain Imaging: In Vitro Evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Alvarado, M.; Biegon, A.

    2001-01-01

    The NMDA receptor has been implicated in neuronal death following stroke, brain injury and neurodegenerative disorders (e.g. Alzheimer's, Parkinson's and Huntington's disease) and in physiological functions (e.g. memory and cognition). Non-competitive antagonists, such as MK- 801 and CNS-1102, that block the action of glutamate at the NMDA receptor have been shown to be neuroprotective by blocking the influx of calcium into the cells. As a result, they are being considered as therapeutic agents for the above mentioned diseases. Several Fluorine-containing novel analogs of NMDA channel blockers have been synthesized and evaluated in search of a compound suitable for 18F labeling and Positron Emission Tomography (PET). Based on in vitro binding assay studies on rat brain membranes, the novel compounds examined displayed a range of affinities. Preliminary analyses indicated that chlorine is the best halogen on the ring, and that ethyl fluoro derivatives are more potent than methyl-fluoro compounds. Further analysis based on autoradiography will be needed to examine the regional binding characteristics of the novel compounds examined in this study. Labeling with 18F will allow the use of these compounds in humans, generating new insights into mechanisms and treatment of diseases involving malfunction of the glutamatergic system in the brain.

  3. Excitotoxic lesions of the tegmental pedunculopontine nucleus impair copulation in naive male rats and block the rewarding effects of copulation in experienced male rats.

    Science.gov (United States)

    Kippin, Tod E; van der Kooy, Derek

    2003-11-01

    The tegmental pedunculopontine nucleus (TPP) of the brainstem mediates food reward in food-sated animals and opiate reward in drug-naive animals. In the present study, we examine the effect of excitotoxic lesions of the TPP on sexual behaviour in naive and experienced male rats. Male, Long-Evans rats received either 0.25 micro L injections of NMDA (4.2 micro g/side) or vehicle (shams) into the TPP. In sexually naive males, complete bilateral TPP lesions decreased all measure of copulation (i.e. mounts, intromissions and ejaculations), prevented acquisition of conditioned sexual excitement, decreased approach preference for a receptive female over a non-receptive one, and decreased non-contact erections; unilateral or bilateral posterior-sparing TPP lesions did not affect any of these measures. Conversely, in sexually experienced males, lesions not only failed to disrupt copulation, but also increased conditioned sexual excitement, decreased post-ejaculatory interval and blocked the effect of prolonged copulation on conditioned sexual excitement. Following differential pairing of distinctive environments with and without copulation, sham males with sexual experience displayed a significant preference for the environment paired with copulation, whereas the lesion males with sexual experience displayed a significant aversion for the environment paired with copulation. These findings indicate that the TPP is critical for the acquisition of copulation in naive males and mediates the rewarding consequences of copulation in experienced males. Together these findings demonstrate that the TPP mediates sexual reward, but that sexual experience is not sufficient to produce a deprivation state.

  4. The Isolated Effect of Adductor Canal Block on Quadriceps Femoris Muscle Strength After Total Knee Arthroplasty

    DEFF Research Database (Denmark)

    Sørensen, Johan Kløvgaard; Jæger, Pia; Dahl, Jørgen Berg

    2016-01-01

    BACKGROUND: Using peripheral nerve block after total knee arthroplasty (TKA), without impeding mobility, is challenging. We hypothesized that the analgesic effect of adductor canal block (ACB) could increase the maximum voluntary isometric contraction (MVIC) of the quadriceps femoris muscle after......, expressed as a percentage of postoperative preblock values. In this manner, the effect of the ACB could be isolated from the detrimental effect on muscle strength caused by the surgery. Secondary end points were differences between groups in mobility and pain scores. We planned a subgroup analysis dividing......: ACB improves quadriceps femoris muscle strength, but whether this translates into enhanced mobility is not clearly supported by this study....

  5. Differential antagonism of tetramethylenedisulfotetramine-induced seizures by agents acting at NMDA and GABA{sub A} receptors

    Energy Technology Data Exchange (ETDEWEB)

    Shakarjian, Michael P., E-mail: michael_shakarjian@nymc.edu [Department of Environmental Health Science, School of Health Sciences and Practice, Institute of Public Health, New York Medical College, Valhalla, NY, 10595 (United States); Department of Medicine, Division of Pulmonary and Critical Care Medicine, UMDNJ–Robert Wood Johnson Medical School, Piscataway, NJ 08854 (United States); Velíšková, Jana, E-mail: jana_veliskova@nymc.edu [Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595 (United States); Department of Obstetrics and Gynecology, New York Medical College, Valhalla, NY 10595 (United States); Department of Neurology, New York Medical College, Valhalla, NY 10595 (United States); Stanton, Patric K., E-mail: patric_stanton@nymc.edu [Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595 (United States); Department of Neurology, New York Medical College, Valhalla, NY 10595 (United States); Velíšek, Libor, E-mail: libor_velisek@nymc.edu [Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595 (United States); Department of Neurology, New York Medical College, Valhalla, NY 10595 (United States); Department of Pediatrics, New York Medical College, Valhalla, NY 10595 (United States)

    2012-11-15

    Tetramethylenedisulfotetramine (TMDT) is a highly lethal neuroactive rodenticide responsible for many accidental and intentional poisonings in mainland China. Ease of synthesis, water solubility, potency, and difficulty to treat make TMDT a potential weapon for terrorist activity. We characterized TMDT-induced convulsions and mortality in male C57BL/6 mice. TMDT (ip) produced a continuum of twitches, clonic, and tonic–clonic seizures decreasing in onset latency and increasing in severity with increasing dose; 0.4 mg/kg was 100% lethal. The NMDA antagonist, ketamine (35 mg/kg) injected ip immediately after the first TMDT-induced seizure, did not change number of tonic–clonic seizures or lethality, but increased the number of clonic seizures. Doubling the ketamine dose decreased tonic–clonic seizures and eliminated lethality through a 60 min observation period. Treating mice with another NMDA antagonist, MK-801, 0.5 or 1 mg/kg ip, showed similar effects as low and high doses of ketamine, respectively, and prevented lethality, converting status epilepticus EEG activity to isolated interictal discharges. Treatment with these agents 15 min prior to TMDT administration did not increase their effectiveness. Post-treatment with the GABA{sub A} receptor allosteric enhancer diazepam (5 mg/kg) greatly reduced seizure manifestations and prevented lethality 60 min post-TMDT, but ictal events were evident in EEG recordings and, hours post-treatment, mice experienced status epilepticus and died. Thus, TMDT is a highly potent and lethal convulsant for which single-dose benzodiazepine treatment is inadequate in managing electrographic seizures or lethality. Repeated benzodiazepine dosing or combined application of benzodiazepines and NMDA receptor antagonists is more likely to be effective in treating TMDT poisoning. -- Highlights: ► TMDT produces convulsions and lethality at low doses in mice. ► Diazepam pre- or post-treatments inhibit TMDT-induced convulsions and death

  6. Effects of channel blocking on information transmission and energy efficiency in squid giant axons.

    Science.gov (United States)

    Liu, Yujiang; Yue, Yuan; Yu, Yuguo; Liu, Liwei; Yu, Lianchun

    2018-04-01

    Action potentials are the information carriers of neural systems. The generation of action potentials involves the cooperative opening and closing of sodium and potassium channels. This process is metabolically expensive because the ions flowing through open channels need to be restored to maintain concentration gradients of these ions. Toxins like tetraethylammonium can block working ion channels, thus affecting the function and energy cost of neurons. In this paper, by computer simulation of the Hodgkin-Huxley neuron model, we studied the effects of channel blocking with toxins on the information transmission and energy efficiency in squid giant axons. We found that gradually blocking sodium channels will sequentially maximize the information transmission and energy efficiency of the axons, whereas moderate blocking of potassium channels will have little impact on the information transmission and will decrease the energy efficiency. Heavy blocking of potassium channels will cause self-sustained oscillation of membrane potentials. Simultaneously blocking sodium and potassium channels with the same ratio increases both information transmission and energy efficiency. Our results are in line with previous studies suggesting that information processing capacity and energy efficiency can be maximized by regulating the number of active ion channels, and this indicates a viable avenue for future experimentation.

  7. Effect of Adductor Canal Block Versus Femoral Nerve Block on Quadriceps Strength, Mobilization, and Pain After Total Knee Arthroplasty

    DEFF Research Database (Denmark)

    Grevstad, Jens Ulrik; Mathiesen, Ole; Valentiner, Laura Risted Staun

    2015-01-01

    BACKGROUND AND OBJECTIVES: Total knee arthroplasty (TKA) is often associated with severe pain. Different regional anesthetic techniques exist, all with varying degrees of motor blockade. We hypothesized that pain relief provided by the adductor canal block (ACB) could increase functional muscle...... strength. METHODS: We included 50 TKA patients with severe movement-related pain; defined as having visual analog scale pain score of greater than 60 mm during active flexion of the knee. The ACB group received an ACB with ropivacaine 0.2% 30 mL and a femoral nerve block (FNB) with 30 mL saline. The FNB...... to ambulate and changes in pain scores (Clinicaltrials.gov identifier NCT01922596). RESULTS: After block, the quadriceps maximum voluntary isometric contraction increased to 193% (95% confidence interval [CI], 143-288) of the baseline value in the ACB group and decreased to 16% (95% CI, 3-33) in the FNB group...

  8. A Methodology for Distinguishing between Extinction and Punishment Effects Associated with Response Blocking.

    Science.gov (United States)

    Lerman, Dorothea C.; Iwata, Brian A.

    1996-01-01

    This paper presents a method for distinguishing between extinction and punishment effects. In extinction and punishment, different schedules of reinforcement or punishment are in effect when a given proportion of responses is blocked. Response patterns in treatment of hand mouthing in an adult with profound mental retardation suggest that a…

  9. Role of NMDA receptors in the increase of glucose metabolism in the rat brain induced by fluorocitrate.

    Science.gov (United States)

    Hirose, Shinichiro; Umetani, Yukiko; Amitani, Misato; Hosoi, Rie; Momosaki, Sotaro; Hatazawa, Jun; Gee, Antony; Inoue, Osamu

    2007-03-30

    The effect of inhibition of glial metabolism by infusion of fluorocitrate (FC, 1 nmol/microl, 2 microl) into the right striatum of the rat brain on the glucose metabolism was studied. Significant increases in [(18)F]fluorodeoxyglucose ([(18)F]FDG) uptake (45 min) in the right cerebral cortex and striatum were observed 4h after the infusion of FC, both as determined by the tissue dissection method and autoradiography. No significant increase in the initial uptake of [(18)F]FDG (1 min) was seen in the striatum. Pretreatment with dizocilpine (MK-801), an N-methyl-d-aspartate (NMDA) receptor antagonist, reduced [(18)F]FDG uptake in not only FC infused hemisphere but also in the contralateral hemisphere (saline-infused side). The radioactivity concentrations in plasma at 1, 5 and 45 min after the [(18)F]FDG injection were not altered by MK-801. This effect of MK-801 on glucose metabolism observed in the rat brain infused with FC was different from previous reports which indicated an increase in glucose metabolism in some areas of normal rat brain. In addition, the enhancement of glucose metabolism in the striatum induced by FC was almost completely abolished by pretreatment with MK-801. In the cerebral cortex, the relative ratio of radioactivity concentration in the right hemisphere to that in the left hemisphere still remained 1.37 (tissue dissection method) or 1.55 (autoradiography), which indicated that MK-801 partially blocked the effect of FC of enhancing glucose metabolism in this region. These results indicate an important role of NMDA-mediated signal transmission on the increase of glucose utilization induced by inhibition of glial metabolism.

  10. NMDA receptors control vagal afferent excitability in the nucleus of the solitary tract.

    Science.gov (United States)

    Vance, Katie M; Rogers, Richard C; Hermann, Gerlinda E

    2015-01-21

    Previous behavioral studies have demonstrated that presynaptic N-methyl-d-aspartate (NMDA) receptors expressed on vagal afferent terminals are involved in food intake and satiety. Therefore, using in vitro live cell calcium imaging of prelabeled rat hindbrain slices, we characterized which NMDA receptor GluN2 subunits may regulate vagal afferent activity. The nonselective NMDA receptor antagonist d,l-2-amino-5-phosphonopentanoic acid (d,l-AP5) significantly inhibited vagal terminal calcium influx, while the excitatory amino acid reuptake inhibitor d,l-threo-β-benzyloxyaspartic acid (TBOA), significantly increased terminal calcium levels following pharmacological stimulation with ATP. Subunit-specific NMDA receptor antagonists and potentiators were used to identify which GluN2 subunits mediate the NMDA receptor response on the vagal afferent terminals. The GluN2B-selective antagonist, ifenprodil, selectively reduced vagal calcium influx with stimulation compared to the time control. The GluN2A-selective antagonist, 3-chloro-4-fluoro-N-[4-[[2-(phenylcarbonyl)hydrazino]carbonyl] benzyl]benzenesulfonamide (TCN 201) produced smaller but not statistically significant effects. Furthermore, the GluN2A/B-selective potentiator (pregnenolone sulfate) and the GluN2C/D-selective potentiator [(3-chlorophenyl)(6,7-dimethoxy-1-((4-methoxyphenoxy)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)methanone; (CIQ)] enhanced vagal afferent calcium influx during stimulation. These data suggest that presynaptic NMDA receptors with GluN2B, GluN2C, and GluN2D subunits may predominantly control vagal afferent excitability in the nucleus of the solitary tract. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. NMDA Reduces Tau Phosphorylation in Rat Hippocampal Slices by Targeting NR2A Receptors, GSK3β, and PKC Activities

    Science.gov (United States)

    Elhiri, Ismaël; Allyson, Julie; Cyr, Michel; Massicotte, Guy

    2013-01-01

    The molecular mechanisms that regulate Tau phosphorylation are complex and currently incompletely understood. In the present study, pharmacological inhibitors were deployed to investigate potential processes by which the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors modulates Tau phosphorylation in rat hippocampal slices. Our results demonstrated that Tau phosphorylation at Ser199-202 residues was decreased in NMDA-treated hippocampal slices, an effect that was not reproduced at Ser262 and Ser404 epitopes. NMDA-induced reduction of Tau phosphorylation at Ser199-202 was further promoted when NR2A-containing receptors were pharmacologically isolated and were completely abrogated by the NR2A receptor antagonist NVP-AAM077. Compared with nontreated slices, we observed that NMDA receptor activation was reflected in high Ser9 and low Tyr216 phosphorylation of glycogen synthase kinase-3 beta (GSK3β), suggesting that NMDA receptor activation might diminish Tau phosphorylation via a pathway involving GSK3β inhibition. Accordingly, we found that GSK3β inactivation by a protein kinase C- (PKC-) dependent mechanism is involved in the NMDA-induced reduction of Tau phosphorylation at Ser199-202 epitopes. Taken together, these data indicate that NR2A receptor activation may be important in limiting Tau phosphorylation by a PKC/GSK3β pathway and strengthen the idea that these receptors might act as an important molecular device counteracting neuronal cell death mechanisms in various pathological conditions. PMID:24349798

  12. Dynamic photoinduced realignment processes in photoresponsive block copolymer films: effects of the chain length and block copolymer architecture.

    Science.gov (United States)

    Sano, Masami; Shan, Feng; Hara, Mitsuo; Nagano, Shusaku; Shinohara, Yuya; Amemiya, Yoshiyuki; Seki, Takahiro

    2015-08-07

    A series of block copolymers composed of an amorphous poly(butyl methacrylate) (PBMA) block connected with an azobenzene (Az)-containing liquid crystalline (PAz) block were synthesized by changing the chain length and polymer architecture. With these block copolymer films, the dynamic realignment process of microphase separated (MPS) cylinder arrays of PBMA in the PAz matrix induced by irradiation with linearly polarized light was studied by UV-visible absorption spectroscopy, and time-resolved grazing incidence small angle X-ray scattering (GI-SAXS) measurements using a synchrotron beam. Unexpectedly, the change in the chain length hardly affected the realignment rate. In contrast, the architecture of the AB-type diblock or the ABA-type triblock essentially altered the realignment feature. The strongly cooperative motion with an induction period before realignment was characteristic only for the diblock copolymer series, and the LPL-induced alignment change immediately started for triblock copolymers and the PAz homopolymer. Additionally, a marked acceleration in the photoinduced dynamic motions was unveiled in comparison with a thermal randomization process.

  13. Adrenergic receptor effects and antihypertensive actions of beta-adrenoceptor-blocking agents with ancillary properties.

    Science.gov (United States)

    Imai, S; Nakahara, H; Nakazawa, M; Takeda, K

    1988-01-01

    The acute antihypertensive effects and possible underlying mechanisms of 3 beta-adrenergic-blocking drugs with alpha-blocking activity, i.e. labetalol, drugs with alpha-blocking activity, i.e. labetalol, nipradilol and arotinolol, were studied in conscious spontaneously hypertensive rats (SHR) and compared with the effects of prazosin, propranolol and hydralazine. Prazosin produced a dose-dependent antihypertensive effect which paralleled inhibition of the pressor response to phenylephrine. Labetalol (30 mg/kg), nipradilol (30 and 100 mg/kg) and arotinolol (30 and 100 mg/kg) also produced a fall in blood pressure. However, inhibition of the pressor response to phenylephrine was not seen in association with the antihypertensive effect after the lower dose of nipradilol and arotinolol. Propranolol (100 mg/kg) did not lower blood pressure. These results suggest that a mechanism(s) other than an alpha-adrenergic-blocking effect plays a role in the acute antihypertensive effects produced by the lower dose of nipradilol and arotinolol.

  14. Stochastic hybrid model of spontaneous dendritic NMDA spikes

    International Nuclear Information System (INIS)

    Bressloff, Paul C; Newby, Jay M

    2014-01-01

    Following recent advances in imaging techniques and methods of dendritic stimulation, active voltage spikes have been observed in thin dendritic branches of excitatory pyramidal neurons, where the majority of synapses occur. The generation of these dendritic spikes involves both Na + ion channels and M-methyl-D-aspartate receptor (NMDAR) channels. During strong stimulation of a thin dendrite, the resulting high levels of glutamate, the main excitatory neurotransmitter in the central nervous system and an NMDA agonist, modify the current-voltage (I–V) characteristics of an NMDAR so that it behaves like a voltage-gated Na + channel. Hence, the NMDARs can fire a regenerative dendritic spike, just as Na + channels support the initiation of an action potential following membrane depolarization. However, the duration of the dendritic spike is of the order 100 ms rather than 1 ms, since it involves slow unbinding of glutamate from NMDARs rather than activation of hyperpolarizing K + channels. It has been suggested that dendritic NMDA spikes may play an important role in dendritic computations and provide a cellular substrate for short-term memory. In this paper, we consider a stochastic, conductance-based model of dendritic NMDA spikes, in which the noise originates from the stochastic opening and closing of a finite number of Na + and NMDA receptor ion channels. The resulting model takes the form of a stochastic hybrid system, in which membrane voltage evolves according to a piecewise deterministic dynamics that is coupled to a jump Markov process describing the opening and closing of the ion channels. We formulate the noise-induced initiation and termination of a dendritic spike in terms of a first-passage time problem, under the assumption that glutamate unbinding is negligible, which we then solve using a combination of WKB methods and singular perturbation theory. Using a stochastic phase-plane analysis we then extend our analysis to take proper account of the

  15. Effect of hexane on magnetic blocking behavior of FePt nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Simsek, Telem, E-mail: telem@hacettepe.edu.tr [SNTG Laboratory, Department of Physics Engineering, Hacettepe University, 06800 Beytepe Ankara (Turkey); Akansel, Serkan, E-mail: akansel@hacettepe.edu.tr [SNTG Laboratory, Department of Physics Engineering, Hacettepe University, 06800 Beytepe Ankara (Turkey); Oezcan, Sadan, E-mail: sadan@hacettepe.edu.tr [SNTG Laboratory, Department of Physics Engineering, Hacettepe University, 06800 Beytepe Ankara (Turkey)

    2012-11-15

    In this work effect of the carrier fluid, hexane, on the magnetic properties of 4.7 nm sized FePt nanoparticles is investigated. Nanoparticles are synthesized by chemical method. Structural and magnetic characterizations confirmed that samples are monodispersed with disordered face centered cubic (fcc) crystal structure and, magnetically, exhibit two blocking behaviors; the first is at 27 K and second at 110 K. Carrier fluid of particles, hexane, is found to influence the blocking of 7% of the total magnetic moments in the system by freezing at low temperatures resulting in a two blocking phenomena even for nanoparticles that are monodispersed with narrow particle size distribution. - Highlights: Black-Right-Pointing-Pointer We investigate the effect of excess hexane on spin relaxation mechanism of single domain FePt nanoparticles. Black-Right-Pointing-Pointer We report that uncomplete evaporation of carrier fluid hexane blocks 7% of total magnetic moment to relax above blocking temperature. Black-Right-Pointing-Pointer This kind of systems could be further used as magnetic switches by controlling.

  16. GDNF and neublastin protect against NMDA-induced excitotoxicity in hippocampal slice cultures

    DEFF Research Database (Denmark)

    Bonde, C; Kristensen, B W; Blaabjerg, M

    2000-01-01

    The potential neuroprotective effects of glial cell line-derived neurotrophic factor (GDNF) and neublastin (NBN) against NMDA-induced excitotoxicity were examined in hippocampal brain slice cultures. Recombinant human GDNF (25-100 ng/ ml) or NBN, in medium conditioned by growth of transfected, NBN...

  17. A unified computational account of cumulative semantic, semantic blocking, and semantic distractor effects in picture naming.

    Science.gov (United States)

    Roelofs, Ardi

    2018-03-01

    Computational models of lexical selection in spoken word production have been applied to semantic interference effects in picture naming response times obtained with continuous naming, blocked-cyclic naming, and picture-word interference paradigms. However, a unified computational account of the effects in the three paradigms is lacking. Here, I show that the inclusion of conceptual bias in the WEAVER++model (Levelt, Roelofs, & Meyer, 1999) explains cumulative semantic and semantic blocking effects while preserving the model's account of semantic distractor effects. The key assumptions of the account are (1) lexical selection by competition, and (2) a conceptual origin and lexical locus of the semantic effects. I provide a proof of concept of the account by reporting computer simulation results, addressing behavioral and neuroimaging evidence. The assumptions are sufficient for a unified account of semantic effects in the three paradigms, contrary to pessimistic views of this area. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. The inhibitory potency of local anesthetics on NMDA receptor signalling depends on their structural features

    NARCIS (Netherlands)

    Gronwald, Carsten; Vegh, Vladimir; Hollmann, Markus W.; Hahnenkamp, Anke; Garaj, Vladimir; Hahnenkamp, Klaus

    2012-01-01

    Development of postoperative hyperalgesia depends on N-methyl-D-aspartate (NMDA) receptor activation. Local anesthetics protect against those hyperalgesic pain states and inhibit NMDA receptor activation. To outline what structural features of local anesthetics are responsible for NMDA receptor

  19. Double dissociation of spike timing-dependent potentiation and depression by subunit-preferring NMDA receptor antagonists in mouse barrel cortex.

    Science.gov (United States)

    Banerjee, Abhishek; Meredith, Rhiannon M; Rodríguez-Moreno, Antonio; Mierau, Susanna B; Auberson, Yves P; Paulsen, Ole

    2009-12-01

    Spike timing-dependent plasticity (STDP) is a strong candidate for an N-methyl-D-aspartate (NMDA) receptor-dependent form of synaptic plasticity that could underlie the development of receptive field properties in sensory neocortices. Whilst induction of timing-dependent long-term potentiation (t-LTP) requires postsynaptic NMDA receptors, timing-dependent long-term depression (t-LTD) requires the activation of presynaptic NMDA receptors at layer 4-to-layer 2/3 synapses in barrel cortex. Here we investigated the developmental profile of t-LTD at layer 4-to-layer 2/3 synapses of mouse barrel cortex and studied their NMDA receptor subunit dependence. Timing-dependent LTD emerged in the first postnatal week, was present during the second week and disappeared in the adult, whereas t-LTP persisted in adulthood. An antagonist at GluN2C/D subunit-containing NMDA receptors blocked t-LTD but not t-LTP. Conversely, a GluN2A subunit-preferring antagonist blocked t-LTP but not t-LTD. The GluN2C/D subunit requirement for t-LTD appears to be synapse specific, as GluN2C/D antagonists did not block t-LTD at horizontal cross-columnar layer 2/3-to-layer 2/3 synapses, which was blocked by a GluN2B antagonist instead. These data demonstrate an NMDA receptor subunit-dependent double dissociation of t-LTD and t-LTP mechanisms at layer 4-to-layer 2/3 synapses, and suggest that t-LTD is mediated by distinct molecular mechanisms at different synapses on the same postsynaptic neuron.

  20. Effect of Systematic Hydrogenation on the Phase Behavior and Nanostructural Dimensions of Block Copolymers.

    Science.gov (United States)

    Ashraf, Arman R; Ryan, Justin J; Satkowski, Michael M; Smith, Steven D; Spontak, Richard J

    2018-01-31

    Unsaturated polydienes are frequently hydrogenated to yield polyolefins that are more chemically stable. Here, the effects of partial hydrogenation on the phase behavior and nanostructure of polyisoprene-containing block copolymers are investigated. To ensure access to the order-disorder transition temperature (T ODT ) over a wide temperature range, we examine copolymers with at least one random block. Dynamic rheological and scattering measurements indicate that T ODT increases linearly with increasing hydrogenation. Small-angle scattering reveals that the temperature-dependence of the Flory-Huggins parameter changes and the microdomain period increases, while the interfacial thickness decreases. The influence of hydrogenation becomes less pronounced in more constrained multiblock copolymers.

  1. On thermal vibration effects in diffusion model calculations of blocking dips

    International Nuclear Information System (INIS)

    Fuschini, E.; Ugozzoni, A.

    1983-01-01

    In the framework of the diffusion model, a method for calculating blocking dips is suggested that takes into account thermal vibrations of the crystal lattice. Results of calculations of the diffusion factor and the transverse energy distribution taking into accoUnt scattering of the channeled particles at thermal vibrations of lattice nuclei, are presented. Calculations are performed for α-particles with the energy of 2.12 MeV at 300 K scattered by Al crystal. It is shown that calculations performed according to the above method prove the necessity of taking into account effects of multiple scattering under blocking conditions

  2. The effects of interleaving versus blocking on foreign language pronunciation learning.

    Science.gov (United States)

    Carpenter, Shana K; Mueller, Frank E

    2013-07-01

    Many studies have shown that students learn better when they are given repeated exposures to different concepts in a way that is shuffled or interleaved, rather than blocked (e.g., Rohrer Educational Psychology Review, 24, 355-367, 2012). The present study explored the effects of interleaving versus blocking on learning French pronunciations. Native English speakers learned several French words that conformed to specific pronunciation rules (e.g., the long "o" sound formed by the letter combination "eau," as in bateau), and these rules were presented either in blocked fashion (bateau, carreau, fardeau . . . mouton, genou, verrou . . . tandis, verglas, admis) or in interleaved fashion (bateau, mouton, tandis, carreau, genou, verglas . . .). Blocking versus interleaving was manipulated within subjects (Experiments 1-3) or between subjects (Experiment 4), and participants' pronunciation proficiency was later tested through multiple-choice tests (Experiments 1, 2, and 4) or a recall test (Experiment 3). In all experiments, blocking benefited the learning of pronunciations more than did interleaving, and this was true whether participants learned only 4 words per rule (Experiments 1-3) or 15 words per rule (Experiment 4). Theoretical implications of these findings are discussed.

  3. The Relationship Between the Renin-Angiotensin-Aldosterone System and NMDA Receptor-Mediated Signal and the Prevention of Retinal Ganglion Cell Death.

    Science.gov (United States)

    Kobayashi, Mamoru; Hirooka, Kazuyuki; Ono, Aoi; Nakano, Yuki; Nishiyama, Akira; Tsujikawa, Akitaka

    2017-03-01

    Excitotoxicity, which is due to glutamate-induced toxic effects on the retinal ganglion cell (RGC), is one of several mechanisms of RGC loss. The renin-angiotensin-aldosterone system (RAAS) has also been implicated in RGC death. Therefore, it is important to determine the exact relationship between the RAAS and N-methyl-d-aspartate (NMDA) receptor-mediated signal in order to prevent RGC death. N-methyl-d-aspartate or aldosterone was injected into the vitreous body. After intravitreal injection of NMDA or aldosterone, animals were treated with spironolactone or memantine. Retinal damage was evaluated by measuring the number of RGCs at 4 weeks after local administration of aldosterone or at 2 weeks after local administration of NMDA. Vitreous humor levels of aldosterone were measured using enzyme immunoassay kits. A significantly decreased number of RGCs were observed after intravitreal injection of NMDA. Although spironolactone did not show any neuroprotective effects, memantine significantly reduced NMDA-induced degeneration in the retina. Furthermore, a significant decrease in the number of RGCs was observed after an intravitreal injection of aldosterone. While memantine did not exhibit any neuroprotective effects, spironolactone caused a significant reduction in the aldosterone-induced degeneration in the retina. There was no change in the aldosterone concentration in the vitreous humor after an NMDA injection. Our findings indirectly show that there is no relationship between the RAAS and NMDA receptor-mediated signal with regard to RGC death.

  4. Ipsilateral transversus abdominis plane block provides effective analgesia after appendectomy in children: a randomized controlled trial.

    LENUS (Irish Health Repository)

    Carney, John

    2010-10-01

    The transversus abdominis plane (TAP) block provides effective postoperative analgesia in adults undergoing major abdominal surgery. Its efficacy in children remains unclear, with no randomized clinical trials in this population. In this study, we evaluated its analgesic efficacy over the first 48 postoperative hours after appendectomy performed through an open abdominal incision, in a randomized, controlled, double-blind clinical trial.

  5. Clinical effects of botulinum toxin A and phenol block on gait in children with cerebral palsy.

    Science.gov (United States)

    Wong, Alice M K; Chen, Chia-Ling; Chen, Carl P C; Chou, Shih-Wei; Chung, Chia-Ying; Chen, Max J L

    2004-04-01

    To compare the treatment effectiveness of botulinum toxin type A (BTX-A) and phenol blocks in managing lower limb spasticity and gait dysfunction in children with cerebral palsy. This is a case-controlled study that took place in a tertiary center's gait laboratory. A total of 27 ambulatory children with cerebral palsy spastic diplegia, aged from 3 to 7 yrs, and 20 normal children were recruited into this study. Sixteen children with cerebral palsy received BTX-A injections, and 11 received phenol motor point blocks. Gait analyses were assessed by a portable computer-assisted system (Computer DynoGraphy, Infotronic, The Netherlands). Both the BTX-A and phenol groups received gait analysis at 1 wk before and 2 mos after injection treatments. Significant improvements in gait variables of velocity and cadence were noted in children with cerebral palsy after BTX-A injections as compared with the phenol block group. Gaitline and cyclogram patterns also improved significantly in the BTX-A group. The adverse clinical effects of BTX-A injections were less severe as compared with phenol injections. BTX-A injections demonstrated superior treatment effects in improving gait variables and patterns in children with spastic diplegia as compared with phenol blocks. BTX-A injections also revealed fewer clinical side effects and were well tolerated by children with cerebral palsies.

  6. Analgesic effect of ultrasound-guided transversus abdominis plane block after total abdominal hysterectomy

    DEFF Research Database (Denmark)

    Røjskjaer, Jesper O; Gade, Erik; Kiel, Louise B

    2015-01-01

    OBJECTIVE: To assess the effect of bilateral ultrasound-guided transversus abdominis plane block with ropivacaine compared with placebo as part of a multimodal analgesic regimen. DESIGN: A randomized, double-blind, placebo-controlled trial following the CONSORT criteria. SETTING: Hvidovre...

  7. Role of the spinal cord NR2B-containing NMDA receptors in the development of neuropathic pain.

    Science.gov (United States)

    Qu, Xiao-Xiu; Cai, Jie; Li, Ming-Jia; Chi, Ye-Nan; Liao, Fei-Fei; Liu, Feng-Yu; Wan, You; Han, Ji-Sheng; Xing, Guo-Gang

    2009-02-01

    Activation of N-methyl-d-aspartate (NMDA) receptors in the spinal dorsal horn has been shown to be essential for the initiation of central sensitization and the hyperexcitability of dorsal horn neurons in chronic pain. However, whether the spinal NR2B-containing NMDA (NMDA-2B) receptors are involved still remains largely unclear. Using behavioral test and in vivo extracellular electrophysiological recording in L5 spinal nerve-ligated (SNL) neuropathic rats, we investigate the roles of spinal cord NMDA-2B receptors in the development of neuropathic pain. Our study showed that intrathecal (i.t.) injection of Ro 25-6981, a selective NMDA-2B receptor antagonist, had a dose-dependent anti-allodynic effect without causing motor dysfunction. Furthermore, i.t. application of another NMDA-2B receptor antagonist ifenprodil prior to SNL also significantly inhibited the mechanical allodynia but not the thermal hyperalgesia. These data suggest that NMDA-2B receptors at the spinal cord level play an important role in the development of neuropathic pain, especially at the early stage following nerve injury. In addition, spinal administration of Ro 25-6981 not only had a dose-dependent inhibitory effect on the C-fiber responses of dorsal horn wide dynamic range (WDR) neurons in both normal and SNL rats, but also significantly inhibited the long-term potentiation (LTP) in the C-fiber responses of WDR neurons induced by high-frequency stimulation (HFS) applied to the sciatic nerve. These results indicate that activation of the dorsal horn NMDA-2B receptors may be crucial for the spinal nociceptive synaptic transmission and for the development of long-lasting spinal hyperexcitability following nerve injury. In conclusion, the spinal cord NMDA-2B receptors play a role in the development of central sensitization and neuropathic pain via the induction of LTP in dorsal horn nociceptive synaptic transmission. Therefore, the spinal cord NMDA-2B receptor is likely to be a target for

  8. NMDA Receptors in Glial Cells: Pending Questions

    Czech Academy of Sciences Publication Activity Database

    Džamba, Dávid; Honsa, Pavel; Anděrová, Miroslava

    2013-01-01

    Roč. 11, č. 3 (2013), s. 250-262 ISSN 1570-159X R&D Projects: GA ČR GA309/08/1381; GA ČR(CZ) GBP304/12/G069 Grant - others:GA UK(CZ) 604212 Institutional support: RVO:68378041 Keywords : astrocytes * ischemia * NMDA receptors Subject RIV: FH - Neurology Impact factor: 2.347, year: 2013

  9. Effective Block-Scale Dispersion and Its Self-Averaging Behavior in Heterogeneous Porous Media

    Science.gov (United States)

    de Barros, Felipe; Dentz, Marco

    2015-04-01

    Upscaled (effective) dispersion coefficients in spatially heterogeneous flow fields must (1) account for the sub-scale variability that is filtered out by homogenization and (2) be modeled as a random function to incorporate the uncertainty associated with non-ergodic solute bodies. In this study, we use the framework developed in de Barros and Rubin (2011) [de Barros F.P.J. and Rubin Y., Modelling of block-scale macrodispersion as a random function. Journal of Fluid Mechanics 676 (2011): 514-545] to develop novel semi-analytical expressions for the first two statistical moments of the block-effective dispersion coefficients in three-dimensional spatially random flow fields as a function of the key characteristic length scales defining the transport problem. The derived expressions are based on perturbation theory and limited to weak-to-mild heterogeneity and uniform-in-the-mean steady state flow fields. The semi-analytical solutions provide physical insights of the main controlling factors influencing the temporal scaling of the dispersion coefficient of the solute body and its self-averaging dispersion behavior. Our results illustrate the relevance of the joint influence of the block-scale and local-scale dispersion in diminishing the macrodispersion variance under non-ergodic conditions. The impact of the statistical anisotropy ratio in the block-effective macrodispersion self-averaging behavior is also investigated. The analysis performed in this work has implications in numerical modeling and grid design.

  10. Blocking effect of colloids on arsenate adsorption during co-transport through saturated sand columns.

    Science.gov (United States)

    Ma, Jie; Guo, Huaming; Lei, Mei; Wan, Xiaoming; Zhang, Hanzhi; Feng, Xiaojuan; Wei, Rongfei; Tian, Liyan; Han, Xiaokun

    2016-06-01

    Transport of environmental pollutants through porous media is influenced by colloids. Co-transport of As(V) and soil colloids at different pH were systematically investigated by monitoring breakthrough curves (BTCs) in saturated sand columns. A solute transport model was applied to characterize transport and retention sites of As(V) in saturated sand in the presence of soil colloids. A colloid transport model and the DLVO theory were used to reveal the mechanism and hypothesis of soil colloid-promoted As(V) transport in the columns. Results showed that rapid transport of soil colloids, regulated by pH and ionic strength, promoted As(V) transport by blocking As(V) adsorption onto sand, although soil colloids had low adsorption for As(V). The promoted transport was more significant at higher concentrations of soil colloids (between 25 mg L(-1) and 150 mg L(-1)) due to greater blocking effect on As(V) adsorption onto the sand surfaces. The blocking effect of colloids was explained by the decreases in both instantaneous (equilibrium) As adsorption and first-order kinetic As adsorption on the sand surface sites. The discovery of this blocking effect improves our understanding of colloid-promoted As transport in saturated porous media, which provides new insights into role of colloids, especially colloids with low As adsorption capacity, in As transport and mobilization in soil-groundwater systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. A role beyond learning for NMDA receptors in reward-based decision-making-a pharmacological study using d-cycloserine.

    Science.gov (United States)

    Scholl, Jacqueline; Günthner, Jan; Kolling, Nils; Favaron, Elisa; Rushworth, Matthew Fs; Harmer, Catherine J; Reinecke, Andrea

    2014-11-01

    N-methyl-D-aspartate (NMDA) receptors are known to fulfill crucial functions in many forms of learning and plasticity. More recently, biophysical models, however, have suggested an additional role of NMDA receptors in evidence integration for decision-making, going beyond their role in learning. We designed a task to study the role of NMDA receptors in human reward-guided learning and decision-making. Human participants were assigned to receive either 250 mg of the partial NMDA agonist d-cycloserine (n=20) or matching placebo capsules (n=27). Reward-guided learning and decision-making were assessed using a task in which participants had to integrate learnt and explicitly shown value information to maximize their monetary wins and minimize their losses. To tease apart the effects of NMDA on learning and decision-making we used simple learning models. D-cycloserine shifted decision-making towards a more optimal integration of the learnt and the explicitly shown information, in the absence of a direct learning effect. In conclusion, our results reveal a distinct role for NMDA receptors in reward-guided decision-making. We discuss these findings in the context of NMDA's roles in neuronal super-additivity and as crucial for evidence integration for decisions.

  12. Investigating the influence of PFC transection and nicotine on dynamics of AMPA and NMDA receptors of VTA dopaminergic neurons

    Directory of Open Access Journals (Sweden)

    Chen Ting

    2011-10-01

    Full Text Available Abstract Background All drugs of abuse, including nicotine, activate the mesocorticolimbic system that plays critical roles in nicotine reward and reinforcement development and triggers glutamatergic synaptic plasticity on the dopamine (DA neurons in the ventral tegmental area (VTA. The addictive behavior and firing pattern of the VTA DA neurons are thought to be controlled by the glutamatergic synaptic input from prefrontal cortex (PFC. Interrupted functional input from PFC to VTA was shown to decrease the effects of the drug on the addiction process. Nicotine treatment could enhance the AMPA/NMDA ratio in VTA DA neurons, which is thought as a common addiction mechanism. In this study, we investigate whether or not the lack of glutamate transmission from PFC to VTA could make any change in the effects of nicotine. Methods We used the traditional AMPA/NMDA peak ratio, AMPA/NMDA area ratio, and KL (Kullback-Leibler divergence analysis method for the present study. Results Our results using AMPA/NMDA peak ratio showed insignificant difference between PFC intact and transected and treated with saline. However, using AMPA/NMDA area ratio and KL divergence method, we observed a significant difference when PFC is interrupted with saline treatment. One possible reason for the significant effect that the PFC transection has on the synaptic responses (as indicated by the AMPA/NMDA area ratio and KL divergence may be the loss of glutamatergic inputs. The glutamatergic input is one of the most important factors that contribute to the peak ratio level. Conclusions Our results suggested that even within one hour after a single nicotine injection, the peak ratio of AMPA/NMDA on VTA DA neurons could be enhanced.

  13. Areal density effects on the blocking of 3-keV Ne7+ ions guided through nanocapillaries in polymers

    NARCIS (Netherlands)

    Stolterfoht, N.; Hellhammer, R.; Sulik, B.; Juhasz, Z.; Bayer, V.; Trautmann, C.; Bodewits, E.; Reitsma, G.; Hoekstra, R.

    2013-01-01

    We studied blocking effects on ion guiding through nanocapillaries in highly insulating polyethylene terephthalate (PET). The experiments were initiated in view of a previous study with capillaries in polycarbonate (PC) for which strong blocking effects were observed, whereas for PET these effects

  14. Blockade of NR2A-Containing NMDA Receptors Induces Tau Phosphorylation in Rat Hippocampal Slices

    Directory of Open Access Journals (Sweden)

    Julie Allyson

    2010-01-01

    Full Text Available Physiological activation of the N-methyl-D-aspartate (NMDA subtype of glutamate receptors has been proposed to play a key role in both neuronal cell function and dysfunction. In the present study, we used selective NMDA receptor antagonists to investigate the involvement of NR2A and NR2B subunits in the modulatory effect of basal NMDA receptor activity on the phosphorylation of Tau proteins. We observed, in acute hippocampal slice preparations, that blockade of NR2A-containing NMDA receptors by the NR2A antagonist NVP-AAM077 provoked the hyperphosphorylation of a residue located in the proline-rich domain of Tau (i.e., Ser199. This effect seemed to be Ser199 specific as there was no increase in phosphorylation at Ser262 and Ser409 residues located in the microtubule-binding and C-terminal domains of Tau proteins, respectively. From a mechanistic perspective, our study revealed that blockade of NR2A-containing receptors influences Tau phosphorylation probably by increasing calcium influx into neurons, which seems to rely on accumulation of new NR1/NR2B receptors in neuronal membranes and could involve the cyclin-dependent kinase 5 pathway.

  15. Monosodium glutamate alters the response properties of rat trigeminovascular neurons through activation of peripheral NMDA receptors.

    Science.gov (United States)

    O'Brien, Melissa; Cairns, Brian E

    2016-10-15

    Ingestion of monosodium glutamate (MSG) has been shown to cause headaches in healthy individuals and trigger migraine-like headaches in migraine sufferers. We combined immunohistochemistry, in vivo electrophysiology, and laser Doppler recordings of dural vasculature to investigate the effect of systemic administration of MSG on the trigeminovascular pathway. Immunohistochemical analysis confirmed the expression of NMDA receptors on nerve fibers innervating dural blood vessels and excitatory amino acid transporter 2 on dural blood vessels. Systemic administration of MSG (50mg/kg) evoked an increase in ongoing discharge in 5/6 spinal trigeminal subnucleus caudalis (SpVc) neurons with dural input recorded from male and female rats, respectively, as well as lowering their mechanical activation threshold. There were no sex-related differences in these effects of MSG. Neuronal discharge and mechanical sensitization were significantly attenuated by co-injection with the peripherally restricted NMDA receptor antagonist (2R)-amino-5-phosphonovaleric acid (APV) in both sexes. Systemic administration of MSG induced a 24.5% and 20.6% increase in dural flux in male and female rats, respectively. These results suggest that MSG-induced headache is mediated by the activation of peripheral NMDA receptors and subsequent dural vasodilation. Peripheral NMDA receptors are a potential target for the development of new drugs to treat headaches. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Effects of Grafting Density on Block Polymer Self-Assembly: From Linear to Bottlebrush.

    Science.gov (United States)

    Lin, Tzu-Pin; Chang, Alice B; Luo, Shao-Xiong; Chen, Hsiang-Yun; Lee, Byeongdu; Grubbs, Robert H

    2017-11-28

    Grafting density is an important structural parameter that exerts significant influences over the physical properties of architecturally complex polymers. In this report, the physical consequences of varying the grafting density (z) were studied in the context of block polymer self-assembly. Well-defined block polymers spanning the linear, comb, and bottlebrush regimes (0 ≤ z ≤ 1) were prepared via grafting-through ring-opening-metathesis polymerization. ω-Norbornenyl poly(d,l-lactide) and polystyrene macromonomers were copolymerized with discrete comonomers in different feed ratios, enabling precise control over both the grafting density and molecular weight. Small-angle X-ray scattering experiments demonstrate that these graft block polymers self-assemble into long-range-ordered lamellar structures. For 17 series of block polymers with variable z, the scaling of the lamellar period with the total backbone degree of polymerization (d* ∼ N bb α ) was studied. The scaling exponent α monotonically decreases with decreasing z and exhibits an apparent transition at z ≈ 0.2, suggesting significant changes in the chain conformations. Comparison of two block polymer systems, one that is strongly segregated for all z (System I) and one that experiences weak segregation at low z (System II), indicates that the observed trends are primarily caused by the polymer architectures, not segregation effects. A model is proposed in which the characteristic ratio (C ∞ ), a proxy for the backbone stiffness, scales with N bb as a function of the grafting density: C ∞ ∼ N bb f(z) . The scaling behavior disclosed herein provides valuable insights into conformational changes with grafting density, thus introducing opportunities for block polymer and material design.

  17. Evaluation of Effect of Pudendal Nerve Block on Post Hemmorrhoidectomy Pain

    Directory of Open Access Journals (Sweden)

    M.H. Sarmast Shoshtari

    2008-10-01

    Full Text Available Introduction & Objective: Hemorrhoid is one of the most common anorectal disease which presents with pain, bleeding and mass protrusion from anus. One of the most important reasons to avoid operation in these patients fears of the pain. Pain control specially during the first 24 hour postoperation period results in decreasing urinary retension and constipation as well as increasing patients pleasant. In this study we assisted the effect of pudendal nerve block to reduce pain in posthemorrhoidectomy period and compared with those patients without pudendal nerve block.Materials & Methods: We randomized 120 patients with average age of 37.7 year who referred to the hospitals of Ahwaz university for hemorrhoidectomy into 2 groups (N1: 60 N2:60. In the first group pudendal nerve block was done but in the second group we didn't. Then pain scores by analogue scale method were calculated in each group at 2, 6, 12& 24 hours after operations. The scores were matched with Chi- Square test. Also we calculated and compared the dosages of injected narcotics.Results: The average pain scores at 2, 6, 12, 24 hours after operation in the first group (with nerve block. Were 2.53, 2.4, 1.91, 2.7, 2.38, and in the second group (without nerve block were 3.43, 3.23, 2.98, 2.81, 3.11. The average of narcotic dosage in the first group was 0.69 and in the second group was 1.3. P-value in two groups in those times were 0.001, 0.002, 0.001, 0.66. P-value for comparison of two groups was 0.01. P-value for comparison of narcotic consumption was 0.003Conclusions: In this study, we showed that pudendal nerve block in post hemorrhoidectomy period, reduced pain significantly and decreased narcotic consumption as well.

  18. An estimation of the minimum effective anesthetic volume of 2% lidocaine in ultrasound-guided axillary brachial plexus block.

    LENUS (Irish Health Repository)

    O'Donnell, Brian D

    2009-07-01

    Ultrasound guidance facilitates precise needle and injectate placement, increasing axillary block success rates, reducing onset times, and permitting local anesthetic dose reduction. The minimum effective volume of local anesthetic in ultrasound-guided axillary brachial plexus block is unknown. The authors performed a study to estimate the minimum effective anesthetic volume of 2% lidocaine with 1:200,000 epinephrine (2% LidoEpi) in ultrasound-guided axillary brachial plexus block.

  19. N-Methyl D-Aspartic Acid (NMDA Receptors and Depression

    Directory of Open Access Journals (Sweden)

    Enver Yusuf Sivrioglu

    2009-06-01

    Full Text Available The monoaminergic hypothesis of depression has provided the basis for extensive research into the pathophysiology of mood disorders and has been of great significance for the development of effective antidepressants. Current antidepressant treatments not only increase serotonin and/or noradrenaline bioavailability but also originate adaptive changes increasing synaptic plasticity. Novel approaches to depression and to antidepressant therapy are now focused on intracellular targets that regulate neuroplasticity and cell survival. Accumulating evidence indicates that there is an anatomical substrate for such a devastating neuropsychiatric disease as major depression. Loss of synaptic plasticity and hippocampal atrophy appear to be prominent features of this highly prevalent disorder. A combination of genetic susceptibility and environmental factors make hippocampal neurons more vulnerable to stress. Abundant experimental evidence indicates that stress causes neuronal damage in brain regions, notably in hippocampal subfields. Stress-induced activation of glutamatergic transmission may induce neuronal cell death through excessive stimulation of N-methyl-D-aspartic acid (NMDA receptors. Recent studies mention that the increase of nitric oxide synthesis and inflammation in major depression may contribute to neurotoxicity through NMDA receptor. Both standard antidepressants and NMDA receptor antagonists are able to prevent stress-induced neuronal damage. NMDA antagonists are effective in widely used animal models of depression and some of them appear to be effective also in the few clinical trials performed to date. We are still far from understanding the complex cellular and molecular events involved in mood disorders. There appears to be an emerging role for glutamate neurotransmission in the search for the pathogenesis of major depression. Attenuation of NMDA receptor function mechanism appears to be a promising target in the search for a more

  20. Topiramate via NMDA, AMPA/kainate, GABAAand Alpha2 receptors and by modulation of CREB/BDNF and Akt/GSK3 signaling pathway exerts neuroprotective effects against methylphenidate-induced neurotoxicity in rats.

    Science.gov (United States)

    Motaghinejad, Majid; Motevalian, Manijeh; Fatima, Sulail; Beiranvand, Tabassom; Mozaffari, Shiva

    2017-11-01

    Chronic abuse of methylphenidate (MPH) often causes neuronal cell death. Topiramate (TPM) carries neuroprotective effects, but its exact mechanism of action remains unclear. In the present study, the role of various doses of TPM and its possible mechanisms, receptors and signaling pathways involved against MPH-induced hippocampal neurodegeneration were evaluated in vivo. Thus, domoic acid (DOM) was used as AMPA/kainate receptor agonist, bicuculline (BIC) as GABA A receptor antagonist, ketamine (KET) as NMDA receptor antagonist, yohimbine (YOH) as α 2 adrenergic receptor antagonist and haloperidol (HAL) was used as dopamine D 2 receptor antagonist. Open field test (OFT) was used to investigate the disturbances in motor activity. Hippocampal neurodegenerative parameters were evaluated. Protein expressions of CREB/BDNF and Akt/GSK3 signaling pathways were also evaluated. Cresyl violet staining was performed to show and confirm the changes in the shape of the cells. TPM (70 and 100 mg/kg) reduced MPH-induced rise in lipid peroxidation, oxidized form of glutathione (GSSG), IL-1β and TNF-α levels, Bax expression and motor activity disturbances. In addition, TPM treatment increased Bcl-2 expression, the level of reduced form of glutathione (GSH) and the levels and activities of superoxide dismutase, glutathione peroxidase and glutathione reductase enzymes. TPM also inhibited MPH-induced hippocampal degeneration. Pretreatment of animals with DOM, BIC, KET and YOH inhibited TPM-induced neuroprotection and increased oxidative stress, neuroinflammation, neuroapoptosis and neurodegeneration while reducing CREB, BDNF and Akt protein expressions. Also pretreatment with DOM, BIC, KET and YOH inhibited TPM-induced decreases in GSK3. It can be concluded that the mentioned receptors by modulation of CREB/BDNF and Akt/GSK3 pathways, are involved in neuroprotection of TPM against MPH-induced neurodegeneration.

  1. GluN2B-containing NMDA receptors contribute to the beneficial effects of hydrogen sulfide on cognitive and synaptic plasticity deficits in APP/PS1 transgenic mice.

    Science.gov (United States)

    Yang, Yuan-Jian; Zhao, Ying; Yu, Bin; Xu, Guo-Gang; Wang, Wei; Zhan, Jin-Qiong; Tang, Zhen-Yu; Wang, Ting; Wei, Bo

    2016-10-29

    Alzheimer's disease (AD) is the most common type of clinical dementia. Previous studies have demonstrated that hydrogen sulfide (H2S) is implicated with the pathology of AD, and exogenous H2S attenuates spatial memory impairments in AD animal models. However, the molecular mechanism by which H2S improves cognition in AD has not been fully explored. Here, we report that chronic administration of sodium hydrosulfide (NaHS, a H2S donor) elevated hippocampal H2S levels and enhanced hippocampus-dependent contextual fear memory and novel object recognition in amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice. In parallel with these behavioral results, treating transgenic mice with NaHS reversed impaired hippocampal long-term potentiation (LTP), which is deemed as the neurobiological basis of learning and memory. At the molecular level, we found that treatment with NaHS did not affect the expression of the GluN1 and GluN2A subunits of NMDA receptor (NMDAR), but did prevent the downregulation of GluN2B subunit and restored its synaptic abundance, response and downstream signaling in the hippocampus in transgenic mice. Moreover, applying Ro 25-6981, a specific GluN2B antagonist, abolished the beneficial effects of NaHS on cognitive performance and hippocampal LTP in transgenic mice. Collectively, our results indicate that H2S can reverse cognitive and synaptic plasticity deficits in AD model mice by restoring surface GluN2B expression and the function of GluN2B-containing NMDARs. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Effects of Interscalene Nerve Block for Postoperative Pain Management in Patients after Shoulder Surgery

    Directory of Open Access Journals (Sweden)

    Hsiu-Pin Chen

    2015-01-01

    Full Text Available Objectives. Shoulder surgery can produce severe postoperative pain and movement limitations. Evidence has shown that regional nerve block is an effective management for postoperative shoulder pain. The purpose of this study was to investigate the postoperative analgesic effect of intravenous patient-controlled analgesia (PCA combined with interscalene nerve block in comparison to PCA alone after shoulder surgery. Methods. In this study, 103 patients receiving PCA combined with interscalene nerve block (PCAIB and 48 patients receiving PCA alone after shoulder surgery were included. Patients’ characteristics, preoperative shoulder score and range of motion, surgical and anesthetic condition in addition to visual analog scale (VAS pain score, postoperative PCA consumption, and adverse outcomes were evaluated. Results. The results showed that PCA combined with interscalene nerve block (PCAIB group required less volume of analgesics than PCA alone group in 24 hours (57.76±23.29 mL versus 87.29±33.73 mL, p<0.001 and 48 hours (114.86±40.97 mL versus 183.63±44.83 mL, p<0.001 postoperatively. The incidence of dizziness in PCAIB group was significantly lower than PCA group (resp., 1.9% and 14.6%, p=0.005. VAS, nausea, and vomiting were less in group PCAIB, but in the absence of significant statistical correlation. Conclusion. Interscalene nerve block is effective postoperatively in reducing the demand for PCA analgesics and decreasing opioids-induced adverse events following shoulder surgery.

  3. Gene regulation by NMDA receptor activation in the SDN-POA neurons of male rats during sexual development.

    Science.gov (United States)

    Hsu, Hseng-Kuang; Shao, Pei-Lin; Tsai, Ke-Li; Shih, Huei-Chuan; Lee, Tzu-Ying; Hsu, Chin

    2005-04-01

    The present study was designed to identify possible signaling pathways, which may play a role in prevention of neuronal apoptosis in the sexually dimorphic nucleus of the preoptic area (SDN-POA) after physiological activation of the N-methyl-D-aspartate (NMDA) receptor. Gene response to the blockage of the NMDA receptor by an antagonist (dizocilpine hydrogen maleate; MK-801) was screened after suppression subtractive hybridization (SSH). The results showed that differential screening after SSH detected the presence of some neurotrophic genes (RNA binding motif protein 3 (RBM3), alpha-tubulin) as well as apoptosis-related genes (Bcl-2, cytochrome oxidase subunit II, cytochrome oxidase subunit III) in the SDN-POA of male rats, which were down-regulated by blocking the NMDA receptor. The RT-PCR products of the aforementioned genes in MK-801-treated males were significantly less than that in untreated males. In particular, the expression of Bcl-2 mRNA, including Bcl-2 protein, in male rats were significantly suppressed by MK-801 treatment. Moreover, the binding activity of nuclear factor kappaB (NFkappaB) was significantly higher in male rats than in females, but significantly diminished by blocking the NMDA receptor with MK-801 in male rats. No significant difference in cAMP response element-binding protein (CREB) binding activity was observed among untreated male, MK-801-treated male, untreated female and MK-801-treated female groups. These results suggest that genes regulated by NMDA receptor activation might participate in neuronal growth and/or anti-apoptosis, and support an important signaling pathway of NFkappaB activation and its target gene, Bcl-2, in preventing neuronal apoptosis in the SDN-POA of male rats during sexual development.

  4. In vivo NMDA receptor activation accelerates motor unit maturation, protects spinal motor neurons, and enhances SMN2 gene expression in severe spinal muscular atrophy mice.

    Science.gov (United States)

    Biondi, Olivier; Branchu, Julien; Sanchez, Gabriel; Lancelin, Camille; Deforges, Séverine; Lopes, Philippe; Pariset, Claude; Lécolle, Sylvie; Côté, Jocelyn; Chanoine, Christophe; Charbonnier, Frédéric

    2010-08-25

    Spinal muscular atrophy (SMA), a lethal neurodegenerative disease that occurs in childhood, is caused by the misexpression of the survival of motor neuron (SMN) protein in motor neurons. It is still unclear whether activating motor units in SMA corrects the delay in the postnatal maturation of the motor unit resulting in an enhanced neuroprotection. In the present work, we demonstrate that an adequate NMDA receptor activation in a type 2 SMA mouse model significantly accelerated motor unit postnatal maturation, counteracted apoptosis in the spinal cord, and induced a marked increase of SMN expression resulting from a modification of SMN2 gene transcription pattern. These beneficial effects were dependent on the level of NMDA receptor activation since a treatment with high doses of NMDA led to an acceleration of the motor unit maturation but favored the apoptotic process and decreased SMN expression. In addition, these results suggest that the NMDA-induced acceleration of motor unit postnatal maturation occurred independently of SMN. The NMDA receptor activating treatment strongly extended the life span in two different mouse models of severe SMA. The analysis of the intracellular signaling cascade that lay downstream the activated NMDA receptor revealed an unexpected reactivation of the CaMKII/AKT/CREB (cAMP response element-binding protein) pathway that induced an enhanced SMN expression. Therefore, pharmacological activation of spinal NMDA receptors could constitute a useful strategy for both increasing SMN expression and limiting motor neuron death in SMA spinal cord.

  5. Simulated Space Environment Effects on the Blocking Force of Silicone Adhesive

    Science.gov (United States)

    Boeder, Paul; Mikatarian, Ron; Koontz, Steve; Albyn, Keith; Finckenor, Miria

    2005-01-01

    The International Space Station (ISS) solar arrays utilize MD-944 diode tape to protect the underlying diodes in the solar array panel circuit and also provide thermal conditioning and mechanical support. The diode tape consists of silicone pressure sensitive adhesive (Dow Coming QC-7725) with a protective Kapton over-layer. On-orbit, the Kapton over-layer will erode under exposure to atomic oxygen (AO) and the underlying exposed silicone adhesive will ultimately convert, under additional AO exposure, to a glass like silicate. The current operational plan is to retract ISS solar array P6 and leave it stored under load for a long duration (6 months or more) during ISS assembly. With the Kapton over-layer eroded away, the exposed silicone adhesive must not cause the solar array to stick to itself or cause the solar array to fail during redeployment. Previous testing by Lockheed-Martin Space Systems (LMSS) characterized silicone blocking following exposure to low energy atomic oxygen (AO) in an asher facility, but this is believed to be conservative. An additional series of tests was performed by the Environmental Effects Group at MSFC under direction from the ISS Program Office Environments Team. This test series included high energy AO (5 eV), near ultraviolet (NUV) radiation and ionizing radiation, singly and in combination. Additional samples were exposed to thermal energy AO (tape samples were exposed to each environment constituent individually, put under preload for seven days and then the resulting blocking force was measured using a tensile machine. Additional samples were exposed to AO, NUV and electrons in series and then put under long term (three to ten months) preload to determine the effect of preload duration on the resulting blocking force of the silicone-to-silicone bond. Test results indicate that high energy AO, ultraviolet radiation and electron ionizing radiation exposure all reduce the blocking force for a silicone-to-silicone bond. AO exposure

  6. Effective System for Automatic Bundle Block Adjustment and Ortho Image Generation from Multi Sensor Satellite Imagery

    Science.gov (United States)

    Akilan, A.; Nagasubramanian, V.; Chaudhry, A.; Reddy, D. Rajesh; Sudheer Reddy, D.; Usha Devi, R.; Tirupati, T.; Radhadevi, P. V.; Varadan, G.

    2014-11-01

    Block Adjustment is a technique for large area mapping for images obtained from different remote sensingsatellites.The challenge in this process is to handle huge number of satellite imageries from different sources with different resolution and accuracies at the system level. This paper explains a system with various tools and techniques to effectively handle the end-to-end chain in large area mapping and production with good level of automation and the provisions for intuitive analysis of final results in 3D and 2D environment. In addition, the interface for using open source ortho and DEM references viz., ETM, SRTM etc. and displaying ESRI shapes for the image foot-prints are explained. Rigorous theory, mathematical modelling, workflow automation and sophisticated software engineering tools are included to ensure high photogrammetric accuracy and productivity. Major building blocks like Georeferencing, Geo-capturing and Geo-Modelling tools included in the block adjustment solution are explained in this paper. To provide optimal bundle block adjustment solution with high precision results, the system has been optimized in many stages to exploit the full utilization of hardware resources. The robustness of the system is ensured by handling failure in automatic procedure and saving the process state in every stage for subsequent restoration from the point of interruption. The results obtained from various stages of the system are presented in the paper.

  7. [Antihypertensive effect of arotinolol (S-596), a new adrenergic beta blocking agent, on experimental hypertension].

    Science.gov (United States)

    Hara, Y; Nakahara, H; Miyagishi, A; Nakatani, H

    1983-08-01

    Effects of a new adrenergic beta-blocking agent, arotinolol (S-596), on the blood pressure and heart rate were assessed in comparison with those of other beta-blocking agents in deoxycorticosterone acetate (DOCA)-saline induced and spontaneously hypertensive rats (SHR). The relationship between the antihypertensive effect and the beta- or alpha-adrenoceptor blocking action of S-596 was also investigated in normotensive conscious rats. In the rat, a cannula was implanted chronically in a femoral artery, from which blood pressure was recorded. The test drugs were administered orally once a day for 14 days at several dose levels. The development of hypertension in DOCA-saline treated rats was clearly retarded with the consecutive oral administration of propranolol (100 mg/kg/day) and hydrochlorothiazide (10 mg/kg/day), but not with S-596 (20, 50 and 100 mg/kg/day) or pindolol (10 mg/kg/day). On the other hand, in SHR, S-596 (more than 10 mg/kg/day) propranolol (50 mg/kg/day), pindolol (10 mg/kg/day), labetalol (100 mg/kg/day) and hydrochlorothiazide (10 mg/kg/day) produced definite antihypertensive effects after the chronic administration. In normotensive conscious rats, the vasodepressor responses induced by isoproterenol were reduced by the beta-blocking agents at lower dose levels than those required for development of antihypertensive effects. The acute effects on blood pressure were determined in hypertensive rats during the chronic treatment with the test drugs. In either type of hypertension, S-596, (10-50 mg/kg/day) showed a depressor effect at 4 and/or 8 hr after administration. In normotensive conscious rats, S-596 antagonized the pressor responses to phenylephrine at doses more than 30 mg/kg. It is therefore suggested that an adrenergic alpha-blocking property is at least partly involved in the hypotensive effect of S-596 as labetalol. In the experiment of acute effect in SHR, pindolol and labetalol showed prominent hypotensive effect after the 1st

  8. Involvement of NMDA receptor in low-frequency magnetic field-induced anxiety in mice.

    Science.gov (United States)

    Salunke, Balwant P; Umathe, Sudhir N; Chavan, Jagatpalsingh G

    2014-12-01

    It had been reported that exposure to extremely low-frequency magnetic field (ELFMF) induces anxiety in human and rodents. Anxiety mediates via the activation of N-methyl-d-aspartate (NMDA) receptor, whereas activation of γ-aminobutyric acid (GABA) receptor attenuates the same. Hence, the present study was carried out to understand the contribution of NMDA and/or GABA receptors modulation in ELFMF-induced anxiety for which Swiss albino mice were exposed to ELFMF (50 Hz, 10 G) by subjecting them to Helmholtz coils. The exposure was for 8 h/day for 7, 30, 60, 90 and 120 days. Anxiety level was assessed in elevated plus maze, open field test and social interaction test, on 7th, 30th, 60th, 90th and 120th exposure day, respectively. Moreover, the role of GABA and glutamate in ELFMF-induced anxiety was assessed by treating mice with muscimol [0.25 mg/kg intraperitoneally (i.p.)], bicuculline (1.0 mg/kg i.p.), NMDA (15 mg/kg i.p.) and MK-801 (0.03 mg/kg i.p.), as a GABAA and NMDA receptor agonist and antagonist, respectively. Glutamate receptor agonist exacerbated while inhibitor attenuated the ELFMF-induced anxiety. In addition, levels of GABA and glutamate were determined in regions of the brain viz, cortex, striatum, hippocampus and hypothalamus. Experiments demonstrated significant elevation of GABA and glutamate levels in the hippocampus and hypothalamus. However, GABA receptor modulators did not produce significant effect on ELFMF-induced anxiety and elevated levels of GABA at tested dose. Together, these findings suggest that ELFMF significantly induced anxiety behavior, and indicated the involvement of NMDA receptor in its effect.

  9. Cholesterol modulates open probability and desensitization of NMDA receptors

    Science.gov (United States)

    Korinek, Miloslav; Vyklicky, Vojtech; Borovska, Jirina; Lichnerova, Katarina; Kaniakova, Martina; Krausova, Barbora; Krusek, Jan; Balik, Ales; Smejkalova, Tereza; Horak, Martin; Vyklicky, Ladislav

    2015-01-01

    NMDA receptors (NMDARs) are glutamate-gated ion channels that mediate excitatory neurotransmission in the CNS. Although these receptors are in direct contact with plasma membrane, lipid–NMDAR interactions are little understood. In the present study, we aimed at characterizing the effect of cholesterol on the ionotropic glutamate receptors. Whole-cell current responses induced by fast application of NMDA in cultured rat cerebellar granule cells (CGCs) were almost abolished (reduced to 3%) and the relative degree of receptor desensitization was increased (by seven-fold) after acute cholesterol depletion by methyl-β-cyclodextrin. Both of these effects were fully reversible by cholesterol repletion. By contrast, the responses mediated by AMPA/kainate receptors were not affected by cholesterol depletion. Similar results were obtained in CGCs after chronic inhibition of cholesterol biosynthesis by simvastatin and acute enzymatic cholesterol degradation to 4-cholesten-3-one by cholesterol oxidase. Fluorescence anisotropy measurements showed that membrane fluidity increased after methyl-β-cyclodextrin pretreatment. However, no change in fluidity was observed after cholesterol enzymatic degradation, suggesting that the effect of cholesterol on NMDARs is not mediated by changes in membrane fluidity. Our data show that diminution of NMDAR responses by cholesterol depletion is the result of a reduction of the open probability, whereas the increase in receptor desensitization is the result of an increase in the rate constant of entry into the desensitized state. Surface NMDAR population, agonist affinity, single-channel conductance and open time were not altered in cholesterol-depleted CGCs. The results of our experiments show that cholesterol is a strong endogenous modulator of NMDARs. Key points NMDA receptors (NMDARs) are tetrameric cation channels permeable to calcium; they mediate excitatory synaptic transmission in the CNS and their excessive activation can lead to

  10. Lipid nanoparticles based on butyl-methoxydibenzoylmethane: in vitro UVA blocking effect

    International Nuclear Information System (INIS)

    Niculae, G; Lacatusu, I; Badea, N; Meghea, A

    2012-01-01

    The aim of the present study was to obtain efficient lipid nanoparticles loaded with butyl-methoxydibenzoylmethane (BMDBM) in order to develop cosmetic formulations with enhanced UVA blocking effect. For this purpose, two adequate liquid lipids (medium chain triglycerides and squalene) have been used in combination with two solid lipids (cetyl palmitate and glyceryl stearate) in order to create appropriate nanostructured carriers with a disordered lipid network able to accommodate up to 1.5% BMDBM. The lipid nanoparticles (LNs) were characterized in terms of particle size, zeta potential, entrapment efficiency, loading capacity and in vitro UVA blocking effect. The efficiency of lipid nanoparticles in developing some cosmetic formulations has been evaluated by determining the in vitro erythemal UVA protection factor. In order to quantify the photoprotective effect, some selected cream formulations based on BMDBM-LNs and a conventional emulsion were exposed to photochemical UV irradiation at a low energy to simulate the solar energy during the midday. The results obtained demonstrated the high ability of cream formulations based on BMDBM-LNs to absorb more than 96% of UVA radiation. Moreover, the developed cosmetic formulations manifest an enhanced UVA blocking effect, the erythemal UVA protection factor being four times higher than those specific to conventional emulsions. (paper)

  11. Perceiving blocks of emotional pictures and sounds:Effects on physiological variables

    Directory of Open Access Journals (Sweden)

    Anne-Marie eBrouwer

    2013-06-01

    Full Text Available Most studies on physiological effects of emotion inducing images and sounds examine stimulus locked variables reflecting a state of at most a few seconds. We here aimed to induce longer lasting emotional states using blocks of repetitive visual, auditory and bimodal stimuli corresponding to specific valence and arousal levels. The duration of these blocks enabled us to reliably measure heart rate variability as a possible indicator of arousal. In addition, heart rate and skin conductance were determined without taking stimulus timing into account. Heart rate was higher for pleasant and low arousal stimuli compared to unpleasant and high arousal stimuli. Heart rate variability and skin conductance increased with arousal. Effects of valence and arousal on cardiovascular measures habituated or remained the same over 2-minute intervals whereas the arousal effect on skin conductance increased. We did not find any effect of stimulus modality. Our results indicate that blocks of images and sounds of specific valence and arousal levels consistently influence different physiological parameters. These parameters need not be stimulus locked. We found no evidence for differences in emotion induction between visual and auditory stimuli, nor did we find bimodal stimuli to be more potent than unimodal stimuli. The latter could be (partly due to the fact that our bimodal stimuli were not optimally congruent.

  12. Olfactory bulb glomerular NMDA receptors mediate olfactory nerve potentiation and odor preference learning in the neonate rat.

    Directory of Open Access Journals (Sweden)

    Rebecca Lethbridge

    Full Text Available Rat pup odor preference learning follows pairing of bulbar beta-adrenoceptor activation with olfactory input. We hypothesize that NMDA receptor (NMDAR-mediated olfactory input to mitral cells is enhanced during training, such that increased calcium facilitates and shapes the critical cAMP pattern. Here, we demonstrate, in vitro, that olfactory nerve stimulation, at sniffing frequencies, paired with beta-adrenoceptor activation, potentiates olfactory nerve-evoked mitral cell firing. This potentiation is blocked by a NMDAR antagonist and by increased inhibition. Glomerular disinhibition also induces NMDAR-sensitive potentiation. In vivo, in parallel, behavioral learning is prevented by glomerular infusion of an NMDAR antagonist or a GABA(A receptor agonist. A glomerular GABA(A receptor antagonist paired with odor can induce NMDAR-dependent learning. The NMDA GluN1 subunit is phosphorylated in odor-specific glomeruli within 5 min of training suggesting early activation, and enhanced calcium entry, during acquisition. The GluN1 subunit is down-regulated 3 h after learning; and at 24 h post-training the GluN2B subunit is down-regulated. These events may assist memory stability. Ex vivo experiments using bulbs from trained rat pups reveal an increase in the AMPA/NMDA EPSC ratio post-training, consistent with an increase in AMPA receptor insertion and/or the decrease in NMDAR subunits. These results support a model of a cAMP/NMDA interaction in generating rat pup odor preference learning.

  13. Metabotropic NMDA receptor function is required for NMDA receptor-dependent long-term depression

    NARCIS (Netherlands)

    Nabavi, Sadegh; Kessels, Helmut W.; Alfonso, Stephanie; Aow, Jonathan; Fox, Rocky; Malinow, Roberto

    2013-01-01

    NMDA receptor (NMDAR) activation controls long-term potentiation (LTP) as well as long-term depression (LTD) of synaptic transmission, cellular models of learning and memory. A long-standing view proposes that a high level of Ca(2+) entry through NMDARs triggers LTP; lower Ca(2+) entry triggers LTD.

  14. LOCALIZATION OF NMDA AND AMPA RECEPTORS IN RAT BARREL FIELD

    NARCIS (Netherlands)

    JAARSMA, D; SEBENS, JB; KORF, J

    1991-01-01

    The aim of this study was to asses the distribution of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-S-methyl-4-isoxazole propionic acid (AMPA) receptors in the barrel field of rat primary somatosensory (SI) cortex using light-microscopic in vitro autoradiography. NMDA receptors were labeled

  15. 3D ultrasound estimation of the effective volume for popliteal block at the level of division.

    Science.gov (United States)

    Sala-Blanch, X; Franco, J; Bergé, R; Marín, R; López, A M; Agustí, M

    2017-03-01

    Local anaesthetic injection between the tibial and commmon peroneal nerves within connective tissue sheath results in a predictable diffusion and allows for a reduction in the volume needed to achieve a consistent sciatic popliteal block. Using 3D ultrasound volumetric acquisition, we quantified the visible volume in contact with the nerve along a 5cm segment. We included 20 consecutive patients scheduled for bunion surgery. Ultrasound guided popliteal block was performed using a posterior, out of plane approach at the level of división of the sciatic nerve. Thirty ml of mepivacaine 1.5% and levobupivacaine 0.5% were slowly injected while assessing the injection pressure and the diffusion of the local anaesthetic. Volumetric acquisition was performed before and after the block to quantify the the volume of the sciatic nerve and the volume of the surrounding hypoechoic halo contained inside the connective tissue in a 5cm segment. All blocks were successful within 20min after the injection. The total estimated volume contained inside the common connective tissue sheath was 6.8±2.6cm 3 . Of this, the volume of the halo sorrounding the nerve was 4.4±1.7cm 3 and the volume inside the sciatic nerve was 2.4±1.7cm 3 . The volume of local anaesthetic in close contact with the sciatic nerve can be estimated by volumetric acquisition. Our results suggest that the effective volume of local anaesthetic needed for a successful sciatic popliteal block could be reduced to less than 7ml. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Minimum effective concentration of bupivacaine for axillary brachial plexus block guided by ultrasound.

    Science.gov (United States)

    Takeda, Alexandre; Ferraro, Leonardo Henrique Cunha; Rezende, André Hosoi; Sadatsune, Eduardo Jun; Falcão, Luiz Fernando dos Reis; Tardelli, Maria Angela

    2015-01-01

    The use of ultrasound in regional anesthesia allows reducing the dose of local anesthetic used for peripheral nerve block. The present study was performed to determine the minimum effective concentration (MEC90) of bupivacaine for axillary brachial plexus block. Patients undergoing hand surgery were recruited. To estimate the MEC90, a sequential up-down biased coin method of allocation was used. The bupivacaine dose was 5 mL for each nerve (radial, ulnar, median, and musculocutaneous). The initial concentration was 0.35%. This concentration was changed by 0.05% depending on the previous block; a blockade failure resulted in increased concentration for the next patient; in case of success, the next patient could receive or reduction (0.1 probability) or the same concentration (0.9 probability). Surgical anesthesia was defined as driving force ≤ 2 according to the modified Bromage scale, lack of thermal sensitivity and response to pinprick. Postoperative analgesia was assessed in the recovery room with numeric pain scale and the amount of drugs used within 4h after the blockade. MEC90 was 0.241% [R(2): 0.978, confidence interval: 0.20-0.34%]. No patient, with successful block, reported pain after 4h. This study demonstrated that ultrasound guided axillary brachial plexus block can be performed with the use of low concentration of local anesthetics, increasing the safety of the procedure. Further studies should be conducted to assess blockade duration at low concentrations. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  17. Effect of blocking Rac1 expression in cholangiocarcinoma QBC939 cells

    Directory of Open Access Journals (Sweden)

    Liu Xudong

    2011-05-01

    Full Text Available Cholangiocarcinomas (CCs are malignant tumors that originate from epithelial cells lining the biliary tree and gallbladder. Ras correlative C3 creotoxin substrate 1 (Rac1, a small guanosine triphosphatase, is a critical mediator of various aspects of endothelial cell functions. The objective of the present investigation was to study the effect of blocking Rac1 expression in CCs. Seventy-four extrahepatic CC (ECC specimens and matched adjacent normal mucosa were obtained from the Department of Pathology, Inner Mongolia Medicine Hospital, between 2007 and 2009. Our results showed that the expression of Rac1 was significantly higher (53.12% in tumor tissues than in normal tissues. Western blotting data indicated a significant reduction in Rac1-miRNA cell protein levels. Rac1-miRNA cell growth rate was significantly different at 24, 48, and 72 h after transfection. Flow cytometry analysis showed that Rac1-miRNA cells undergo apoptosis more effectively than control QBC939 cells. Blocking Rac1 expression by RNAi effectively inhibits the growth of CCs. miRNA silencing of the Rac1 gene suppresses proliferation and induces apoptosis of QBC939 cells. These results suggest that Rac1 may be a new gene therapy target for CC. Blocking Rac1 expression in CC cells induces apoptosis of these tumor cells and may thus represent a new therapeutic approach.

  18. MS-377, a selective sigma receptor ligand, indirectly blocks the action of PCP in the N-methyl-D-aspartate receptor ion-channel complex in primary cultured rat neuronal cells.

    Science.gov (United States)

    Karasawa, Jun-ichi; Yamamoto, Hideko; Yamamoto, Toshifumi; Sagi, Naoki; Horikomi, Kazutoshi; Sora, Ichiro

    2002-02-22

    MS-377 ((R)-(+)-1-(4-chlorophenyl)-3-[4-(2-methoxyethyl)piperazin-1-yl]methyl-2-pyrrolidinone L-tartrate) is a antipsychotic agent that binds to sigma-1 receptor. MS-377 showed anti-dopaminergic and anti-serotonergic activities and antagonistic action against phencyclidine (PCP)-induced behaviors in an animal model. These anti-psychotic activities of MS-377 are attributable to association with sigma-1 receptor. However, the mechanism by which the sigma-1 receptor ligands exact those numerous effects remains to be elucidated. In the present study, we evaluated the effect of MS-377 on N-methyl-D-aspartate (NMDA) receptor ion-channel complex in primary cultured rat neuronal cells. First, we examined the effect of MS-377 on NMDA-induced Ca2+ influx with fura-2/ AM loaded cells. MS-377 showed no effects on the basal Ca2+ concentration and NMDA-induced Ca2+ influx by itself PCP and SKF-10047 reduced the NMDA-induced increase in intracellular Ca2+ concentration. Pre-incubation of 1 microM MS-377 was found to significantly block the reduction by PCP or SKF-10047 of the NMDA-induced Ca2+ influx. Second, the effect of MS-377 on [3H]MK-801 intact cell binding was examined. PCP, haloperidol and (+)-pentazocine inhibited [3H]MK-801 binding, although MS-377 showed no effect by itself Pre-treatment of MS-377 markedly reversed the inhibition of [3H]MK-801 binding by PCP in a dose-dependent manner. These effects of MS-377 may depend on its affinity for the sigma-1 receptor, because MS-377 is a selective sigma-1 receptor ligand without any affinity for NMDA receptor ion-channel complex. These observations suggest that the MS-377 indirectly modulated the NMDA receptor ion-channel complex, and the anti-psychotic activities of MS-377, in part, are attributable to such on action via sigma-1 receptor.

  19. A neuroligin-1-derived peptide stimulates phosphorylation of the NMDA receptor NR1 subunit and rescues MK-801-induced decrease in long-term potentiation and memory impairment

    DEFF Research Database (Denmark)

    Korshunova, Irina; Gjørlund, Michelle D; Jacobsen, Sylwia Owczarek

    2015-01-01

    , neurolide-2, reduces sociability and increase animal aggression. We hypothesized that interfering with NL1 function at the excitatory synapses might regulate synaptic plasticity and learning, and counteract memory deficits induced by N-methyl-d-aspartate (NMDA) receptor inhibition. First, neuronal NMDA...... receptor phosphorylation after treatment with NL1 or a mimetic peptide, neurolide-1, was quantified by immunoblotting. Subsequently, we investigated effects of neurolide-1 on long-term potentiation (LTP) induction in hippocampal slices compromised by NMDA receptor inhibitor MK-801. Finally, we investigated...... neurolide-1 effects on short- and long-term social and spatial memory in social recognition, Morris water-maze, and Y-maze tests. We found that subcutaneous neurolide-1 administration, restored hippocampal LTP compromised by NMDA receptor inhibitor MK-801. It counteracted MK-801-induced memory deficit...

  20. Effect of brain-derived neurotrophic factor on activity-regulated cytoskeleton-associated protein gene expression in primary frontal cortical neurons. Comparison with NMDA and AMPA

    DEFF Research Database (Denmark)

    El-Sayed, Mona; Hofman-Bang, Jacob; Mikkelsen, Jens D

    2011-01-01

    The effect of brain-derived neurotrophic factor (BDNF) on activity-regulated cytoskeleton-associated protein (Arc) mRNA levels in primary neuronal cultures of rat frontal cortex was characterized pharmacologically and compared to the effect on expression of c-fos, bdnf, neuritin, cox-2 as examples...

  1. Neuroprotection, excitotoxicicity and nmda antagonists Neuroproteção, excitotoxicidade e antagonistas do NMDA

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    RUBENS JOSÉ GAGLIARDI

    2000-06-01

    Full Text Available PURPOSE: To analyze the main aspects of neuroprotection and excitotoxicity. DISCUSSION: This is a significant theory on the pathophysiology of cerebral ischemia; it is based on the release of excitatory aminoacid (EAA, mainly glutamate. The sequence starts with a decrease of the blood flow and ends in neuronal death. The main stages of this reaction are herein presented and discussed. An in depth study of the effects of the excessive intracellular calcium is undertaken. Neuroprotectors (NP are a group of drugs that reduce the excitotoxicity, opposing the excessive release of EAA and its intracellular effects. Neuroprotectors represent a rational approach to stroke treatment and offer a number of potential advantages. They prevent or limit ischemia-induced damage. CONCLUSION: There are many experimental and clinical NP trials. A minimum of 800 trials are currently under study worldwide. The most important NP subgroups are: N-methyl D-aspartate (NMDA antagonists, gamma-amino butyric acid (GABA agonists, amino-hydroxy-methyl-isoxalone propionic acid (AMPA antagonists, reducers of intracellular Ca++ inhibitors of nitric oxide modulation pathway free radicals scavengers, sodium channel antagonists, glutamate release inhibitor, growth factors, hypothermia and potassium channel activators.PROPÓSITO: Analisar importantes aspectos da neuroproteção e da excitotoxicidade. DISCUSSÃO: Excitotoxicidade é teoria que explica os mecanismos básicos da fisiopatologia da isquemia cerebral; é baseada na liberação excessiva de amino-ácidos excitatórios (AAE, principalmente o glutamato. A sequência se inicia com o decréscimo do fluxo sanguíneo cerebral e termina com a morte neuronal. Os principais aspectos desta cadeia de reações são apresentados e discutidos. Os efeitos do excesso de cálcio intracelular são analisados. Neuroprotetores (NP são um grupo de drogas que reduzem a excitotoxicidade combatendo a excessiva liberação de AAE e os seus

  2. Amphetamine and Dopamine-Induced Immediate Early Gene Expression in Striatal Neurons Depends on Postsynaptic NMDA Receptors and Calcium

    Science.gov (United States)

    Konradi, Christine; Leveque, Jean-Christophe; Hyman, Steven E.

    2014-01-01

    Amphetamine and cocaine induce the expression of both immediate early genes (IEGs) and neuropeptide genes in rat striatum. Despite the demonstrated dependence of these effects on D1 dopamine receptors, which activate the cyclic AMP pathway, there are several reports that amphetamine and cocaine-induced IEG expression can be inhibited in striatum in vivo by NMDA receptor antagonists. We find that in vivo, the NMDA receptor antagonist MK-801 inhibits amphetamine induction of c-fos acutely and also prevents downregulation of IEG expression with chronic amphetamine administration. Such observations raise the question of whether dopamine/glutamate interactions occur at the level of corticostriatal and mesostriatal circuitry or within striatal neurons. Therefore, we studied dissociated striatal cultures in which midbrain and cortical presynaptic inputs are removed. In these cultures, we find that dopamine- or forskolin-mediated IEG induction requires Ca2+ entry via NMDA receptors but not via L-type Ca2+ channels. Moreover, blockade of NMDA receptors diminishes the ability of dopamine to induce phosphorylation of the cyclic AMP responsive element binding protein CREB. Although these results do not rule out a role for circuit-level dopamine/glutamate interactions, they demonstrate a requirement at the cellular level for interactions between the cyclic AMP and NMDA receptor pathways in dopamine-regulated gene expression in striatal neurons. PMID:8753884

  3. Is transverse abdominis plane block effective following local anesthetic infiltration in laparoscopic totally extraperitoneal hernia repair?

    Science.gov (United States)

    Kim, Mun Gyu; Kim, Soon Im; Ok, Si Young; Kim, Sang Ho; Lee, Se-Jin; Park, Sun Young; Yoo, Jae-Hwa; Cho, Ana; Hur, Kyung Yul; Kim, Myung Jin

    2014-12-01

    Transverse abdominis plane (TAP) block can be recommended as a multimodal method to reduce postoperative pain in laparoscopic abdominal surgery. However, it is unclear whether TAP block following local anesthetic infiltration is effective. We planned this study to evaluate the effectiveness of the latter technique in laparoscopic totally extraperitoneal hernia repair (TEP). We randomly divided patients into two groups: the control group (n = 37) and TAP group (n = 37). Following the induction of general anesthesia, as a preemptive method, all of the patients were subjected to local anesthetic infiltration at the trocar sites, and the TAP group was subjected to ultrasound-guided bilateral TAP block with 30 ml of 0.375% ropivacaine in addition before TEP. Pain was assessed in the recovery room and post-surgery at 4, 8, and 24 h. Additionally, during the postoperative 24 h, the total injected dose of analgesics and incidence of nausea were recorded. On arrival in the recovery room, the pain score of the TAP group (4.33 ± 1.83) was found to be significantly lower than that of the control group (5.73 ± 2.04). However, the pain score was not significantly different between the TAP group and control group at 4, 8, and 24 h post-surgery. The total amounts of analgesics used in the TAP group were significantly less than in the control group. No significant difference was found in the incidence of nausea between the two groups. TAP block following local infiltration had a clinical advantage only in the recovery room.

  4. Effect of tramadol as an adjuvant to local anesthetics for brachial plexus block: A systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Hye Won Shin

    Full Text Available Tramadol, a 4-phenyl-piperidine analog of codeine, has a unique action in that it has a central opioidergic, noradrenergic, serotonergic analgesic, and peripheral local anesthetic (LA effect. Many studies have reported contradictory findings regarding the peripheral analgesic effect of tramadol as an adjuvant to LA in brachial plexus block (BPB. This meta-analysis aimed to evaluate the effects of tramadol as an adjunct to LA in BPB during shoulder or upper extremity surgery.We searched the PubMed, EMBASE, Cochrane, KoreaMed databases, and Google Scholar for eligible randomized controlled trials (RCTs that compared BPB with LA alone and BPB with LA and tramadol. Primary outcomes were the effects of tramadol as an adjuvant on duration of sensory block, motor block, and analgesia. Secondary outcomes were the effects of tramadol as an adjuvant on time to onset of sensory block and motor block and on adverse effects. We performed the meta-analysis using Review Manager 5.3 software.We identified 16 RCTs with 751 patients. BPB with tramadol prolonged the duration of sensory block (mean difference [MD], -61.5 min; 95% CI, -95.5 to -27.6; P = 0.0004, motor block (MD, -65.6 min; 95% CI, -101.5 to -29.7; P = 0.0003, and analgesia (MD, -125.5 min; 95% CI, -175.8 to -75.3; P < 0.0001 compared with BPB without tramadol. Tramadol also shortened the time to onset of sensory block (MD, 2.1 min; 95% CI, 1.1 to 3.1; P < 0.0001 and motor block (MD, 1.2 min; 95% CI, 0.2 to 2.1; P = 0.010. In subgroup analysis, the duration of sensory block, motor block, and analgesia was prolonged for BPB with tramadol 100 mg (P < 0.05 but not for BPB with tramadol 50 mg. The quality of evidence was high for duration of analgesia according to the GRADE system. Adverse effects were comparable between the studies.In upper extremity surgery performed under BPB, use of tramadol 100 mg as an adjuvant to LA appears to prolong the duration of sensory block, motor block, and analgesia, and

  5. The Effects of Opposition and Gender on Knee Kinematics and Ground Reaction Force during Landing from Volleyball Block Jumps

    Science.gov (United States)

    Hughes, Gerwyn; Watkins, James; Owen, Nick

    2010-01-01

    The aim of this study was to examine the effect of opposition and gender on knee kinematics and ground reaction force during landing from a volleyball block jump. Six female and six male university volleyball players performed two landing tasks: (a) an unopposed and (b) an opposed volleyball block jump and landing. A 12-camera motion analysis…

  6. Effect of addition of magnesium to local anesthetics for peribulbar block: A prospective randomized double-blind study.

    Science.gov (United States)

    Sinha, R; Sharma, A; Ray, B R; Chandiran, R; Chandralekha, C; Sinha, R

    2016-01-01

    Magnesium sulphate has been used along with local anesthetics in different regional blocks and found to be effective in decreasing the time of onset of the block and increasing the duration of the block. To evaluate the effect of addition of magnesium sulfate to standard local anesthetics mixture on the time for onset of the globe and lid akinesia for peribulbar block in ophthalmic surgeries. Sixty patients with American Society of Anesthesiologists status I to III undergoing ophthalmic surgery under peribulbar block were included in this study. Patients were randomized into two groups. Both the groups received 4.5 ml of 2% lidocaine, 4.5 ml of 0.5% bupivacaine with150 IU hyaluronidase. Group NS received normal saline 1 ml in the peribulbar block and Group MS, magnesium sulfate 50 mg in 1 ml normal saline. The onset of akinesia, satisfactory block and complications were observed by an independent observer. Demographic data was statistically similar. In the Group NS at 3, 5, 10 and 15 min after the block, complete akinesia was seen in 0, 2, 11 and 28 patients respectively. In the Group MS, at 3, 5, 10 and 15 min after the block, complete akinesia was seen in 13, 23, 27 and 28 patients respectively. Patients received magnesium sulfate showed the statistically significant rapid onset of lid and globe akinesia than the control group till 10 min (P block and had complications during the surgery. Addition of 50 mg of magnesium sulfate to the lidocaine-bupivacaine mixture for peribulbar block decreases the onset of akinesia without any obvious side effect.

  7. Effect of Banana Fibers on the Compressive and Flexural Strength of Compressed Earth Blocks

    Directory of Open Access Journals (Sweden)

    Marwan Mostafa

    2015-03-01

    Full Text Available Sustainable development of the built environment in developing countries is a major challenge in the 21st century. The use of local materials in construction of buildings is one of the potential ways to support sustainable development in both urban and rural areas. Building with Compressed Earthen Blocks (CEBs is becoming more popular due to their low cost and relative abundance of materials. The proposed Green-Compressed Earth Block (GCEB consists of ordinary CEB ingredients plus Banana fibers, which will be the focus of this study. Banana fibers are widely available worldwide as agricultural waste from Banana cultivation. Banana fibers are environmentally friendly and present important attributes, such as low density, light weight, low cost, high tensile strength, as well as being water and fire resistant. This kind of waste has a greater chance of being utilized for different application in construction and building materials. This focused on the use of banana fiber and its effect on the compressive and flexural strength in CEB. The deflection at the mid-span of the blocks studied was calculated using the Linear Variable Differential Transformer (LVDT. The results of this study will highlight general trends in the strength properties of different soil mixes for CEBs. These efforts are necessary to ensure that GCEB technology becomes more widely accepted in the world of building materials and is considered a reliable option for providing low-cost housing.

  8. Comparison of the Effects of Total Nasal Block and Central Facial Block on Acute Postoperative Pain, Edema, and Ecchymosis After Septorhinoplasty.

    Science.gov (United States)

    Sari, Elif; Simsek, Gokce

    2015-12-01

    Pain, ecchymosis, and edema are major postoperative transient complications of septorhinoplasty procedures. They increase the patient's anxiety and decrease satisfaction levels as well as extend recovery time in the early postoperative period. The aim of this study was to compare the effects of total nasal block (TNB) and central facial block (CFB) on postoperative pain, edema, and ecchymosis. A total of 60 consecutive patients enrolled in this study and were divided into three groups as Controls (n = 20), TNB (n = 20), and CFB (n = 20). The two block methods mentioned above were performed at both the beginning and end of the surgery in the TNB and CFB groups. The Control group was not subjected to any block methods. Pain, edema, and ecchymosis score results according to the three scales were recorded postoperatively after 24 h, and on days 2, 5, 7, and 10. Results were analyzed statistically. Of all patients, 28 were male and 32 were female. Ages were between 18 and 52 years (mean = 26.3 years). Pain, edema, and ecchymosis scores were significantly lower in the TNB and CFB groups than in the Control group. Additionally, there was a significant difference between the TNB and CFB groups in terms of pain and edema at postoperative 24 h and on day 2. Ecchymosis scores were lower in the CFB group than in the TNB group at 24 h and on days 2 and 5 after the operation. Both TNB and CFB decreased postoperative pain, edema, and ecchymosis in septorhinoplasty. However, CFB was more effective than TNB in terms of pain, edema, and ecchymosis relief after septorhinoplasty procedures. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

  9. [Minimum effective concentration of bupivacaine for axillary brachial plexus block guided by ultrasound].

    Science.gov (United States)

    Takeda, Alexandre; Ferraro, Leonardo Henrique Cunha; Rezende, André Hosoi; Sadatsune, Eduardo Jun; Falcão, Luiz Fernando Dos Reis; Tardelli, Maria Angela

    2015-01-01

    The use of ultrasound in regional anesthesia allows reducing the dose of local anesthetic used for peripheral nerve block. The present study was performed to determine the minimum effective concentration (MEC90) of bupivacaine for axillary brachial plexus block (ABPB). Patients undergoing hand surgery were recruited. To estimate the MEC90, a sequential up-down biased coin method of allocation was used. The bupivacaine dose was 5mL for each nerve (radial, ulnar, median, and musculocutaneous). The initial concentration was 0.35%. This concentration was changed by 0.05% depending on the previous block: a blockade failure resulted in increased concentration for the next patient; in case of success, the next patient could receive or reduction (0.1 probability) or the same concentration (0.9 probability). Surgical anesthesia was defined as driving force ≤ 2 according to the modified Bromage scale, lack of thermal sensitivity and response to pinprick. Postoperative analgesia was assessed in the recovery room with numeric pain scale and the amount of drugs used within 4hours after the blockade. MEC90 was 0.241% [R2: 0.978, confidence interval: 0.20%-0.34%]. No successful block patient reported pain after 4hours. This study demonstrated that ultrasound guided ABPB can be performed with the use of low concentration of local anesthetics, increasing the safety of the procedure. Further studies should be conducted to assess blockade duration at low concentrations. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  10. Distinct presynaptic regulation of dopamine release through NMDA receptors in striosome- and matrix-enriched areas of the rat striatum

    International Nuclear Information System (INIS)

    Krebs, M.O.; Trovero, F.; Desban, M.; Gauchy, C.; Glowinski, J.; Kemel, M.L.

    1991-01-01

    Striosome- and matrix-enriched striatal zones were defined in coronal and sagittal brain sections of the rat, on the basis of 3 H-naloxone binding to mu-opiate receptors (a striosome-specific marker). Then, using a new in vitro microsuperfusion device, the NMDA (50 microM)-evoked release of newly synthesized 3 H-dopamine ( 3 H-DA) was examined in these four striatal areas under Mg(2+)-free conditions. The amplitudes of the responses were different in striosomal (171 +/- 6% and 161 +/- 5% of the spontaneous release) than in matrix areas (223 +/- 6% and 248 +/- 12%), even when glycine (1 or 100 microM) was coapplied (in the presence of 1 microM strychnine). In the four areas, the NMDA-evoked release of 3 H-DA was blocked completely by Mg 2+ (1 mM) or (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate (MK-801; 1 microM) and almost totally abolished by kynurenate (100 microM). Because the tetrodotoxin (TTX)-resistant NMDA-evoked release of 3 H-DA was similar in striosome- (148 +/- 5% and 152 +/- 6%) or matrix-enriched (161 +/- 5% and 156 +/- 7%) areas, the indirect (TTX-sensitive) component of NMDA-evoked responses, which involves striatal neurons and/or afferent fibers, seems more important in the matrix- than in the striosome-enriched areas. The modulation of DA release by cortical glutamate and/or aspartate-containing inputs through NMDA receptors in the matrix appears thus to be partly distinct from that observed in the striosomes, providing some functional basis for the histochemical striatal heterogeneity

  11. Distinct presynaptic regulation of dopamine release through NMDA receptors in striosome- and matrix-enriched areas of the rat striatum

    Energy Technology Data Exchange (ETDEWEB)

    Krebs, M.O.; Trovero, F.; Desban, M.; Gauchy, C.; Glowinski, J.; Kemel, M.L. (College de France, Paris (France))

    1991-05-01

    Striosome- and matrix-enriched striatal zones were defined in coronal and sagittal brain sections of the rat, on the basis of {sup 3}H-naloxone binding to mu-opiate receptors (a striosome-specific marker). Then, using a new in vitro microsuperfusion device, the NMDA (50 microM)-evoked release of newly synthesized {sup 3}H-dopamine ({sup 3}H-DA) was examined in these four striatal areas under Mg(2+)-free conditions. The amplitudes of the responses were different in striosomal (171 +/- 6% and 161 +/- 5% of the spontaneous release) than in matrix areas (223 +/- 6% and 248 +/- 12%), even when glycine (1 or 100 microM) was coapplied (in the presence of 1 microM strychnine). In the four areas, the NMDA-evoked release of {sup 3}H-DA was blocked completely by Mg{sup 2}{sup +} (1 mM) or (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate (MK-801; 1 microM) and almost totally abolished by kynurenate (100 microM). Because the tetrodotoxin (TTX)-resistant NMDA-evoked release of {sup 3}H-DA was similar in striosome- (148 +/- 5% and 152 +/- 6%) or matrix-enriched (161 +/- 5% and 156 +/- 7%) areas, the indirect (TTX-sensitive) component of NMDA-evoked responses, which involves striatal neurons and/or afferent fibers, seems more important in the matrix- than in the striosome-enriched areas. The modulation of DA release by cortical glutamate and/or aspartate-containing inputs through NMDA receptors in the matrix appears thus to be partly distinct from that observed in the striosomes, providing some functional basis for the histochemical striatal heterogeneity.

  12. COMPARISON OF POSTOPERATIVE ANALGESIC EFFECT OF US-GUIDED TRANSVERSES ABDOMINIS PLANE BLOCK WITH PARAVERTEBRAL BLOCK FOR UNILATERAL INGUINAL HERNIA REPAIR IN ADULT PATIENTS UNDER GENERAL ANAESTHESIA

    Directory of Open Access Journals (Sweden)

    Girish Sharma

    2017-10-01

    Full Text Available BACKGROUND Both Transverse Abdominis Plane (TAP block and Paravertebral Block (PVB can be used to provide postoperative analgesia in inguinal hernia surgeries. Present study was done to evaluate the postoperative analgesic effect of USG-guided TAP block with USG-guided PVB for unilateral inguinal hernia repair under general anaesthesia. MATERIALS AND METHODS Sixty, American Society of Anesthesiologist (ASA grade 1 and 2 adult patients undergoing inguinal hernia repair under general anaesthesia were randomly allocated to TAP (Gp I and PVB (Gp II group of 30 each. In Gp I patients received local anaesthetic mixture of 0.5% bupivacaine (15 mL and 2% Xylocaine with adrenaline (15 mL in TAP plane under real time USG. In Gp II, the same anaesthetic mixture was injected 1 cm deep to superior surface of transverse process of T10,12 and L2 vertebra under ultrasound guidance. The postoperative pain using the Visual Analogue Scale (VAS, the number of analgesic doses and total drug requirement in the first 24 hours of postoperative period was noted. Statistical Analysis Used- SPSS version 14.0 (SPSS Inc., Chicago, IL, Chi-square test, Student’s t-test. P ˂0.05 was taken as statistically significant. RESULTS VAS scores were statistically significantly lower in Gp II as compared to Gp1 at 1, 2, 4 and 6 hours postoperative time interval (p value <0.05. The difference in VAS scores became insignificant at 12 and 24 hours of postoperative period. Mean time to first analgesic in postoperative period in Gp I was 5:06 hrs. (range 2-10 hrs. and in Gp II was 7.7 hrs. (range 5-10 hrs. (p value ˂0.001. Twenty two patients in Gp I and ten patients in Gp II required analgesic in postoperative period (p ˂0.001. Total number of diclofenac doses required in postoperative period was significantly lower in Gp II than in Gp I (10 v/s 25. Total dose of diclofenac consumed in first 24 hrs. was significantly lower in Gp II (750 mg than in Gp I (1875 mg (p value ˂0

  13. Effects of loading sequences and size of repeated stress block of loads on fatigue life calculated using fatigue functions

    International Nuclear Information System (INIS)

    Schott, G.

    1989-01-01

    It is well-known that collective form, stress intensity and loading sequence of individual stresses as well as size of repeated stress blocks can influence fatigue life, significantly. The basic variant of the consecutive Woehler curve concept will permit these effects to be involved into fatigue life computation. The paper presented will demonstrate that fatigue life computations using fatigue functions reflect the loading sequence effect with multilevel loading precisely and provide reliable fatigue life data. Effects of size of repeated stress block and loading sequence on fatigue life as observed with block program tests can be reproduced using the new computation method. (orig.) [de

  14. Activation of Transient Receptor Potential Vanilloid 4 Increases NMDA-Activated Current in Hippocampal Pyramidal Neurons.

    Science.gov (United States)

    Li, Lin; Qu, Weijun; Zhou, Libin; Lu, Zihong; Jie, Pinghui; Chen, Lei; Chen, Ling

    2013-01-01

    The glutamate excitotoxicity, mediated through N-methyl-d-aspartate receptors (NMDARs), plays an important role in cerebral ischemia injury. Transient receptor potential vanilloid 4 (TRPV4) can be activated by multiple stimuli that may happen during stroke. The present study evaluated the effect of TRPV4 activation on NMDA-activated current (INMDA) and that of blocking TRPV4 on brain injury after focal cerebral ischemia in mice. We herein report that activation of TRPV4 by 4α-PDD and hypotonic stimulation increased INMDA in hippocampal CA1 pyramidal neurons, which was sensitive to TRPV4 antagonist 10 μ M/2 μ 1/mouse [DOSAGE ERROR CORRECTED] and NMDAR antagonist AP-5, indicating that TRPV4 activation potentiates NMDAR response. In addition, the increase in INMDA by hypotonicity was sensitive to the antagonist of NMDAR NR2B subunit, but not of NR2A subunit. Furthermore, antagonists of calcium/calmodulin-dependent protein kinase II (CaMKII) significantly attenuated hypotonicity-induced increase in INMDA, while antagonists of protein kinase C or casein kinase II had no such effect, indicating that phosphorylation of NR2B subunit by CaMKII is responsible for TRPV4-potentiated NMDAR response. Finally, we found that intracerebroventricular injection of 10 μ m/2 μ 1/mouse [DOSAGE ERROR CORRECTED] after 60 min middle cerebral artery occlusion reduced the cerebral infarction with at least a 12 h efficacious time-window. These findings indicate that activation of TRPV4 increases NMDAR function, which may facilitate glutamate excitotoxicity. Closing TRPV4 may exert potent neuroprotection against cerebral ischemia injury through many mechanisms at least including the prevention of NMDAR-mediated glutamate excitotoxicity.

  15. Dynamic transition on the seizure-like neuronal activity by astrocytic calcium channel block

    International Nuclear Information System (INIS)

    Li, Jiajia; Wang, Rong; Du, Mengmeng; Tang, Jun; Wu, Ying

    2016-01-01

    The involvement of astrocytes in neuronal firing dynamics is becoming increasingly evident. In this study, we used a classical hippocampal tripartite synapse model consisting of soma-dendrite coupled neuron models and a Hodgkin–Huxley-like astrocyte model, to investigate the seizure-like firing in the somatic neuron induced by the over-expressed neuronal N-methyl-d-aspartate (NMDA) receptors. Based on this model, we further investigated the effect of the astrocytic channel block on the neuronal firing through a bifurcation analysis. Results show that blocking inositol-1,4,5-triphosphate(IP3)-dependent calcium channel in astrocytes efficiently suppresses the astrocytic calcium oscillation, which in turn suppresses the seizure-like firing in the neuron.

  16. NMDA receptor function during senescence: implication on cognitive performance

    Directory of Open Access Journals (Sweden)

    Ashok eKumar

    2015-12-01

    Full Text Available N-methyl-D-aspartate (NMDA receptors, a family of L-glutamate receptors, play an important role in learning and memory, and are critical for spatial memory. These receptors are tetrameric ion channels composed of a family of related subunits. One of the hallmarks of the aging human population is a decline in cognitive function; studies in the past couple of years have demonstrated deterioration in NMDA receptor subunit expression and function with advancing age. However, a direct relationship between impaired memory function and a decline in NMDA receptors is still ambiguous. Recent studies indicate a link between an age-associated NMDA receptor hypofunction and memory impairment and provide evidence that age-associated enhanced oxidative stress might be contributing to the alterations associated with senescence. However, clear evidence is still deficient in demonstrating the underlying mechanisms and a relationship between age-associated impaired cognitive faculties and NMDA receptor hypofunction. The current review intends to present an overview of the research findings regarding changes in expression of various NMDA receptor subunits and deficits in NMDA receptor function during senescence and its implication in age-associated impaired hippocampal-dependent memory function.

  17. Ketamine displaces the novel NMDA receptor SPET probe [{sup 123}I]CNS-1261 in humans in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Stone, James M. [Institute of Psychiatry, King' s College London, De Crespigny Park London, SE5 8AF (United Kingdom)]. E-mail: j.stone@iop.kcl.ac.uk; Erlandsson, Kjell [Institute of Nuclear Medicine, University College London, London, W1N 8AA (United Kingdom); Arstad, Erik [Institute of Psychiatry, King' s College London, De Crespigny Park London, SE5 8AF (United Kingdom); Bressan, Rodrigo A. [Institute of Psychiatry, King' s College London, De Crespigny Park London, SE5 8AF (United Kingdom); Squassante, Lisa [GlaxoSmithKline (GSK), Verona 37135 (Italy); Teneggi, Vincenza [GlaxoSmithKline (GSK), Verona 37135 (Italy); Ell, Peter J. [Institute of Nuclear Medicine, University College London, London, W1N 8AA (United Kingdom); Pilowsky, Lyn S. [Institute of Psychiatry, King' s College London, De Crespigny Park London, SE5 8AF (United Kingdom); Institute of Nuclear Medicine, University College London, London, W1N 8AA (United Kingdom)

    2006-02-15

    [{sup 123}I]CNS-1261 [N-(1-naphthyl)-N'-(3-iodophenyl)-N-methylguanidine] is a high-affinity SPET ligand with selectivity for the intrachannel PCP/ketamine/MK-801 site of the N-methyl-D-aspartate (NMDA) receptor. This study evaluated the effects of ketamine (a specific competitor for the intrachannel PCP/ketamine/MK-801 site) on [{sup 123}I]CNS-1261 binding to NMDA receptors in vivo. Ten healthy volunteers underwent 2 bolus-plus-infusion [{sup 123}I]CNS-1261 scans, one during placebo and the other during a ketamine challenge. Ketamine administration led to a significant decrease in [{sup 123}I]CNS-1261 V {sub T} in most of the brain regions examined (P<.05). [{sup 123}I]CNS-1261 appears to be a specific ligand in vivo for the intrachannel PCP/ketamine/MK-801 NMDA binding site.

  18. Role of the NMDA receptor and iron on free radical production and brain damage following transient middle cerebral artery occlusion.

    Science.gov (United States)

    Im, Doo Soon; Jeon, Jeong Wook; Lee, Jin Soo; Won, Seok Joon; Cho, Sung Ig; Lee, Yong Beom; Gwag, Byoung Joo

    2012-05-21

    Excess activation of ionotropic glutamate receptors and iron is believed to contribute to free radical production and neuronal death following hypoxic ischemia. We examined the possibility that both NMDA receptor activation and iron overload determine spatial and temporal patterns of free radical production after transient middle cerebral artery occlusion (tMCAO) in male Sprague-Dawley rats. Mitochondrial free radical (MFR) levels were maximally increased in neurons in the core at 1 h and 24 h after tMCAO. Early MFR production was blocked by administration of MK-801, an NMDA receptor antagonist, but not deferoxamine, an iron chelator. Neither MK-801 nor deferoxamine attenuated late MFR production in the core. Increased MFRs were observed in penumbral neurons within 6 h and gradually increased over 24 h after tMCAO. Slowly-evolving MFRs in the core and penumbra were accompanied by iron overload. Deferoxamine blocked iron overload but reduced MFR production only in the penumbra. Combined MK-801/deferoxamine reduced late MFR production in both core and penumbra in an additive manner. Combination therapy significantly ameliorated infarction compared with monotherapy. These findings suggest that the NMDA receptor activation and iron overload mediate late MFR production and infarction after tMCAO. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Influence of blocking effect and energetic disorder on diffusion in one-dimensional lattice

    International Nuclear Information System (INIS)

    Mai Thi Lan; Nguyen Van Hong; Nguyen Thu Nhan; Hoang Van Hue

    2014-01-01

    The diffusion in one-dimensional disordered lattice with Gaussian distribution of site and transition energies has been studied by mean of kinetic Monte-Carlo simulation. We focus on investigating the influence of energetic disorders and diffusive particle density on diffusivity. In single-particle case, we used both analytical method and kinetic Monte-Carlo simulation to calculate the quantities that relate to diffusive behavior in disordered systems such as the mean time between two consecutive jumps, correlation factor and diffusion coefficient. The calculation shows a good agreement between analytical and simulation results for all disordered lattice types. In many - particle case, the blocking effect results in decreasing correlation factor F and average time τ jump between two consecutive jumps. With increasing the number of particles, the diffusion coefficient D M decreases for site-energy and transition-energy disordered lattices due to the F-effect affect affects stronger than τ-effect. Furthermore, the blocking effect almost is temperature independent for both lattices. (author)

  20. Effects of fuel relocation on reflood in a partially-blocked rod bundle

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Byoung Jae [School of Mechanical Engineering, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134 (Korea, Republic of); Kim, Jongrok; Kim, Kihwan; Bae, Sung Won [Thermal-Hydraulic Safety Research Division, Korea Atomic Energy Research Division, 111 Daedeok-daero, Yuseong-gu, Daejeon 34057 (Korea, Republic of); Moon, Sang-Ki, E-mail: skmoon@kaeri.re.kr [Thermal-Hydraulic Safety Research Division, Korea Atomic Energy Research Division, 111 Daedeok-daero, Yuseong-gu, Daejeon 34057 (Korea, Republic of)

    2017-02-15

    Ballooning of the fuel rods has been an important issue, since it can influence the coolability of the rod bundle in a large-break loss-of-coolant accident (LBLOCA). Numerous past studies have investigated the effect of blockage geometry on the heat transfer in a partially blocked rod bundle. However, they did not consider the occurrence of fuel relocation and the corresponding effect on two-phase heat transfer. Some fragmented fuel particles located above the ballooned region may drop into the enlarged volume of the balloon. Accordingly, the fuel relocation brings in a local power increase in the ballooned region. The present study’s objective is to investigate the effect of the fuel relocation on the reflood under a LBLOCA condition. Toward this end, experiments were performed in a 5 × 5 partially-blocked rod bundle. Two power profiles were tested: one is a typical cosine shape and the other is the modified shape considering the effect of the fuel relocation. For a typical power shape, the peak temperature in the ballooned rods was lower than that in the intact rods. On the other hand, for the modified power shape, the peak temperature in the ballooned rods was higher than that in the intact rods. Numerical simulations were also performed using the MARS code. The tendencies of the peak clad temperatures were well predicted.

  1. Protective effects of Δ9-tetrahydrocannabinol against N-methyl-D-aspartate-induced AF5 cell death

    Science.gov (United States)

    Chen, Jia; Lee, Chun-Ting; Errico, Stacie; Deng, Xiaolin; Cadet, Jean L.; Freed, William J.

    2007-01-01

    The neuroprotective effects of Δ9-tetrahydrocannabinol (THC) were examined using an in vitro model in which the AF5 CNS cell line was exposed to toxic levels of N-methyl-D-aspartate (NMDA), an agonist of the NMDA glutamate receptor. NMDA toxicity was reduced by THC, but not by the more specific cannabinoid receptor agonist, WIN55,212-2. Addition of dibutyryl cAMP (dbcAMP) to the culture medium did not alter the neuroprotective effect of THC and did not unmask a neuroprotective effect of WIN55,212-2. The cannabinoid antagonist SR141716A did not inhibit the neuroprotection induced by THC or alter the response to WIN55,212-2, even in the presence of dbcAMP, indicating that the neuroprotective effect of THC was cannabinoid receptor-independent. On the other hand, both THC and WIN55,212-2 produced cellular toxicology at higher dosages, an effect which was blocked in part by SR141716A. Capsaicin, an antioxidant and vanilloid receptor agonist, also produced a protective effect against NMDA toxicology. The protective effect of capsaicin was blocked by co-application of ruthenium red, but was not blocked by the specific vanilloid receptor antagonist capsazepine, and the transient receptor potential vanilloid type 1 (TRPV1) and ANKTM1 transcripts were not detected in AF5 cells. Thus, the neuroprotective effects of THC and capsaicin did not appear to be mediated by TRP ion channel family receptors. The antioxidant α-tocopherol prevented neurotoxicity in dose-dependent manner. Therefore, THC may function as an antioxidant to increase cell survival in NMDA-induced neurotoxicity in the AF5 cell model, while higher dosages produce toxicity mediated by CB1 receptor stimulation. PMID:15836919

  2. Partial agonists and subunit selectivity at NMDA receptors

    DEFF Research Database (Denmark)

    Risgaard, Rune; Hansen, Kasper Bø; Clausen, Rasmus Prætorius

    2010-01-01

    -methyl-D-aspartic acid (NMDA) receptor class. Development of these ligands seems to be a difficult task because of the conserved region in the binding site of the NMDA receptor subunits. A few scaffolds have been developed showing potential to differentiate between the NMDA receptors.......Subunit-selective ligands for glutamate receptors remains an area of interest as glutamate is the major excitatory neurotransmitter in the brain and involved in a number of diseased states in the central nervous system (CNS). Few subtype-selective ligands are known, especially among the N...

  3. In-Band Interference Effects on UTRA LTE Uplink Resource Block Allocation

    DEFF Research Database (Denmark)

    Priyanto, Basuki Endah; Sørensen, Troels Bundgaard; Jensen, Ole Kiel

    2008-01-01

    In this paper we investigate the impact of in-band interference on the uplink multiple access of UMTS Terrestrial Radio Access, long term evolution (UTRA LTE). In- band and out-of-band interference arise as a result of transmitter imperfections. Out-of- band, or adjacent channel, interference can......, and when the interfering signal is received at higher power spectral density (PSD). The effect of frequency offset and different PSD level from the UE interferers to a victim UE is studied. The impact on different UE resource block size allocation is also investigated. The results are obtained from an LTE...

  4. Entropy-based quantification of a product’s BOM blocking effect

    Directory of Open Access Journals (Sweden)

    César Martínez-Olvera

    2016-01-01

    Full Text Available Manufacturing complexity increases as a result of product configuration, and even though different manufacturing complexity measures have been developed, none of them seem to put attention to the blocking effect a product’s bill-of-material imposes to the process flow. The following paper extends the research presented by the authors in a previous paper, where a set of entropic formulations were developed to act as an increase/decrease indicator of a manufacturing system’s performance parameters. Our findings show that the improvements to the entropic formulations provide results that are closer to the system’s performance parameters final values.

  5. The Effect of Patient Positioning During Administration of 0.5% Isobaric Bupivacaine on Sensory Level Block

    National Research Council Canada - National Science Library

    Domer, Christopher

    1999-01-01

    .... This study was designed to examine the effect of patient position on the subsequent height of sensory block achieved following administration of an isobaric anesthetic solution into the subarachnoid space...

  6. Effect of autonomic blocking agents and structurally related substances on the “salt arousal of drinking”

    NARCIS (Netherlands)

    Wied, D. de

    The effect of autonomic blocking agents and structurally related substances was studied in rats in which thirst was produced by the administration of a hypertonic sodium chloride solution. Scopolamine, methamphetamine, amphetamine, chlorpromazine, atropine, mecamylamine, hexamethonium, nethalide,

  7. Memory effects in annealed hybrid gold nanoparticles/block copolymer bilayers

    Science.gov (United States)

    Torrisi, Vanna; Ruffino, Francesco; Licciardello, Antonino; Grazia Grimaldi, Maria; Marletta, Giovanni

    2011-12-01

    We report on the use of the self-organization process of sputtered gold nanoparticles on a self-assembled block copolymer film deposited by horizontal precipitation Langmuir-Blodgett (HP-LB) method. The morphology and the phase-separation of a film of poly- n-butylacrylate- block-polyacrylic acid (P nBuA- b-PAA) were studied at the nanometric scale by using atomic force microscopy (AFM) and Time of Flight Secondary Ion Mass Spectrometry (TOF-SIMS). The templating capability of the P nBuA- b-PAA phase-separated film was studied by sputtering gold nanoparticles (NPs), forming a film of nanometric thickness. The effect of the polymer chain mobility onto the organization of gold nanoparticle layer was assessed by heating the obtained hybrid P nBuA- b-PAA/Au NPs bilayer at T > T g. The nanoparticles' distribution onto the different copolymer domains was found strongly affected by the annealing treatment, showing a peculiar memory effect, which modifies the AFM phase response of the Au NPs layer onto the polar domains, without affecting their surfacial composition. The effect is discussed in terms of the peculiar morphological features induced by enhanced mobility of polymer chains on the Au NPs layer.

  8. Heat transfer behavior including thermal wake effects in forced air cooling of arrays of rectangular blocks

    International Nuclear Information System (INIS)

    Sridhar, S.; Faghri, M.; Lessmann, R.C.

    1990-01-01

    Experiments have been carried out to study thermal wake effects in arrays of rectangular blocks encountered in electronic equipment. Data were obtained for a series of channel heights and flow velocities. The temperature rise due to wake effects behind a single heated module was found to be fairly independent of the channel height and the position of the heated block, for a given approach velocity. The adiabatic temperature rise data for a module due to a heated element immediately upstream of it for different inter-module spacings were found to correlate well in terms of a new parameter called the surface packing density. This paper reports that it was reported by the authors in an earlier paper that both the adiabatic heat transfer coefficient nd pressure-drop data for regular in-line arrays correlated well in terms of a composite geometric parameter called the column packing density. These experiments have been extended to a higher Reynolds number. Empirical correlations are presented here for friction factor and Nusselt number in terms of the volume packing density, and for the thermal wake effects in terms of the surface packing density. Data from literature for arrays with widely different geometric parameters are shown to agree with these correlations

  9. Memory effects in annealed hybrid gold nanoparticles/block copolymer bilayers

    Directory of Open Access Journals (Sweden)

    Ruffino Francesco

    2011-01-01

    Full Text Available Abstract We report on the use of the self-organization process of sputtered gold nanoparticles on a self-assembled block copolymer film deposited by horizontal precipitation Langmuir-Blodgett (HP-LB method. The morphology and the phase-separation of a film of poly-n-butylacrylate-block-polyacrylic acid (PnBuA-b-PAA were studied at the nanometric scale by using atomic force microscopy (AFM and Time of Flight Secondary Ion Mass Spectrometry (TOF-SIMS. The templating capability of the PnBuA-b-PAA phase-separated film was studied by sputtering gold nanoparticles (NPs, forming a film of nanometric thickness. The effect of the polymer chain mobility onto the organization of gold nanoparticle layer was assessed by heating the obtained hybrid PnBuA-b-PAA/Au NPs bilayer at T >Tg. The nanoparticles' distribution onto the different copolymer domains was found strongly affected by the annealing treatment, showing a peculiar memory effect, which modifies the AFM phase response of the Au NPs layer onto the polar domains, without affecting their surfacial composition. The effect is discussed in terms of the peculiar morphological features induced by enhanced mobility of polymer chains on the Au NPs layer.

  10. The role of neonatal NMDA receptor activation in defeminization and masculinization of sex behavior in the rat

    Science.gov (United States)

    Schwarz, Jaclyn M.; McCarthy, Margaret M.

    2008-01-01

    Normal development of the male rat brain involves two distinct processes, masculinization and defeminization, that occur during a critical period of brain sexual differentiation. Masculinization allows for the capacity to express male sex behavior in adulthood, and defeminization eliminates or suppresses the capacity to express female sex behavior in adulthood. Despite being separate processes, both masculinization and defeminization are induced by neonatal estradiol exposure. Though the mechanisms underlying estradiol-mediated masculinization of behavior during development have been identified, the mechanisms underlying defeminization are still unknown. We sought to determine whether neonatal activation of glutamate NMDA receptors is a necessary component of estradiol-induced defeminization of behavior. We report here that antagonizing glutamate receptors during the critical period of sexual differentiation blocks estradiol-induced defeminization but not masculinization of behavior in adulthood. However, enhancing NMDA receptor activation during the same critical period mimics estradiol to permanently induce both defeminization and masculinization of sexual behavior. PMID:18687334

  11. Effectiveness comparison of inferior alveolar nerve block anesthesia using direct and indirect technique

    Directory of Open Access Journals (Sweden)

    Rehatta Yongki

    2016-12-01

    Full Text Available Local anesthesia is important to do prior to tooth extraction procedure to control the patient's pain. Local anesthetic technique in dentistry consists of topical, infiltration, and anesthetic blocks. For molar tooth extraction, mandibular block technique is used either direct or indirect. This study aimed to see if there are differences in effectiveness of inferior alveolar nerve block anesthesia techniques between direct and indirect. This clinical experimental design study used 20 patients as samples during February-April. 10 patients were taken as a group that carried out direct technique while 10 others group conducted indirect techniques. The sample selection using purposive sampling method. Pain level were measured using objective assessments (pain experienced by the patient after a given stimulus and subjective evaluation (thick taste perceived by the patient. The average time of onset in direct and indirect techniques in each sample was 16.88 ± 5.30 and 102.00 ± 19.56 seconds (subjectively and 22.50 ± 8.02 and 159.00 ± 25.10 (objectively. These results indicated direct techniques onset faster than indirect techniques. The average duration of direct and indirect techniques respectively was 121.63 ± 8.80 and 87.80 ± 9.96 minutes (subjectively and 91.88 ± 8.37 and 60.20 ± 10.40 minutes (objectively. These results indicated the duration of direct technique is longer than indirect technique. There was no significant difference when viewed from anesthesia depth and aspiration level. This study indicated that direct technique had better effect than indirect technique in terms of onset and duration, while in terms of anesthesia depth and aspiration level was relatively equal. Insignificant differences were obtained when assessing anesthetic technique successful rate based on gender, age and extracted tooth.

  12. STUDY OF BLOCKING EFFECT ELIMINATION METHODS BY MEANS OF INTRAFRAME VIDEO SEQUENCE INTERPOLATION

    Directory of Open Access Journals (Sweden)

    I. S. Rubina

    2015-01-01

    Full Text Available The paper deals with image interpolation methods and their applicability to eliminate some of the artifacts related to both the dynamic properties of objects in video sequences and algorithms used in the order of encoding steps. The main drawback of existing methods is the high computational complexity, unacceptable in video processing. Interpolation of signal samples for blocking - effect elimination at the output of the convertion encoding is proposed as a part of the study. It was necessary to develop methods for improvement of compression ratio and quality of the reconstructed video data by blocking effect elimination on the borders of the segments by intraframe interpolating of video sequence segments. The main point of developed methods is an adaptive recursive algorithm application with adaptive-sized interpolation kernel both with and without the brightness gradient consideration at the boundaries of objects and video sequence blocks. Within theoretical part of the research, methods of information theory (RD-theory and data redundancy elimination, methods of pattern recognition and digital signal processing, as well as methods of probability theory are used. Within experimental part of the research, software implementation of compression algorithms with subsequent comparison of the implemented algorithms with the existing ones was carried out. Proposed methods were compared with the simple averaging algorithm and the adaptive algorithm of central counting interpolation. The advantage of the algorithm based on the adaptive kernel size selection interpolation is in compression ratio increasing by 30%, and the advantage of the modified algorithm based on the adaptive interpolation kernel size selection is in the compression ratio increasing by 35% in comparison with existing algorithms, interpolation and quality of the reconstructed video sequence improving by 3% compared to the one compressed without interpolation. The findings will be

  13. Polybenzimidazole block copolymers for fuel cell: synthesis and studies of block length effects on nanophase separation, mechanical properties, and proton conductivity of PEM.

    Science.gov (United States)

    Maity, Sudhangshu; Jana, Tushar

    2014-05-14

    A series of meta-polybenzimidazole-block-para-polybenzimidazole (m-PBI-b-p-PBI), segmented block copolymers of PBI, were synthesized with various structural motifs and block lengths by condensing the diamine terminated meta-PBI (m-PBI-Am) and acid terminated para-PBI (p-PBI-Ac) oligomers. NMR studies and existence of two distinct glass transition temperatures (Tg), obtained from dynamical mechanical analysis (DMA) results, unequivocally confirmed the formation of block copolymer structure through the current polymerization methodology. Appropriate and careful selection of oligomers chain length enabled us to tailor the block length of block copolymers and also to make varieties of structural motifs. Increasingly distinct Tg peaks with higher block length of segmented block structure attributed the decrease in phase mixing between the meta-PBI and para-PBI blocks, which in turn resulted into nanophase segregated domains. The proton conductivities of proton exchange membrane (PEM) developed from phosphoric acid (PA) doped block copolymer membranes were found to be increasing substantially with increasing block length of copolymers even though PA loading of these membranes did not alter appreciably with varying block length. For example when molecular weight (Mn) of blocks were increased from 1000 to 5500 then the proton conductivities at 160 °C of resulting copolymers increased from 0.05 to 0.11 S/cm. Higher block length induced nanophase separation between the blocks by creating less morphological barrier within the block which facilitated the movement of the proton in the block and hence resulting higher proton conductivity of the PEM. The structural varieties also influenced the phase separation and proton conductivity. In comparison to meta-para random copolymers reported earlier, the current meta-para segmented block copolymers were found to be more suitable for PBI-based PEM.

  14. The hippocampal NMDA receptors may be involved in acquisition, but not expression of ACPA-induced place preference.

    Science.gov (United States)

    Nasehi, Mohammad; Sharaf-Dolgari, Elmira; Ebrahimi-Ghiri, Mohaddeseh; Zarrindast, Mohammad-Reza

    2015-12-03

    Numerous studies have investigated the functional interactions between the endocannabinoid and glutamate systems in the hippocampus. The present study was made to test whether N-methyl-D-aspartate (NMDA) receptors of the CA1 region of the dorsal hippocampus (CA1) are implicated in ACPA (a selective cannabinoid CB1 receptor agonist)-induced place preference. Using a 3-day schedule of conditioning, it was found that intraperitoneal (i.p.) administration of ACPA (0.02mg/kg) caused a significant conditioned place preference (CPP) in male albino NMRI mice. Intra-CA1 microinjection of the NMDA or D-[1]-2-amino-7-Phosphonoheptanoic acid (D-AP7, NMDA receptor antagonist), failed to induce CPP or CPA (condition place aversion), while NMDA (0.5μg/mouse) potentiated the ACPA (0.01mg/kg)-induced CPP; and D-AP7 (a specific NMDA receptor antagonist; 0.5 and 1μg/mouse) reversed the ACPA (0.02mg/kg)-induced CPP. Moreover, microinjection of different doses of glutamatergic agents on the testing day did not alter the expression of ACPA-induced place preference. None of the treatments, with the exception of ACPA (0.04mg/kg), had an effect on locomotor activity. In conclusion, these observations provide evidence that glutamate NMDA receptors of the CA1 may be involved in the potentiation of ACPA rewarding properties in the acquisition, but not expression, of CPP in mice. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Social Memory in Mice: Disruption with an NMDA Antagonist and Attenuation with Antipsychotic Drugs

    OpenAIRE

    Gao, Xue-Min; Elmer, Gregory I.; Adams-Huet, Beverley; Tamminga, Carol A.

    2008-01-01

    Social recognition reflects the ability of one animal to learn and remember the identity of another. Animal models of social learning and memory are pertinent to several different CNS diseases involving disruptions in cognition. Moreover, the increased understanding of the basic biology of memory increases the likelihood of discovery of memory-enhancing treatments in these human diseases. In the present study, we investigated the effects of the non-competitive NMDA antagonist ketamine on soci...

  16. Cognitive Decline in Neuronal Aging and Alzheimer's Disease: Role of NMDA Receptors and Associated Proteins

    Directory of Open Access Journals (Sweden)

    Jesús Avila

    2017-11-01

    Full Text Available Molecular changes associated with neuronal aging lead to a decrease in cognitive capacity. Here we discuss these alterations at the level of brain regions, brain cells, and brain membrane and cytoskeletal proteins with an special focus in NMDA molecular changes through aging and its effect in cognitive decline and Alzheimer disease. Here, we propose that some neurodegenerative disorders, like Alzheimer's disease (AD, are characterized by an increase and acceleration of some of these changes.

  17. Effect of eccentric location of the RBMK CPS displacer graphite block in the shielding sheath

    International Nuclear Information System (INIS)

    Dostov, A.I.

    2001-01-01

    Temperature conditions and accumulation of Wigner energy in the graphite block of the RBMK reactor CPS (control power system) displacer is examined. It is shown, that at eccentric location of the block in the shielding sheath average temperature of the block drops sharply. Due to the design demerit quantity of the stored energy in the block may be so great, that its release will result in melting of the displacer tube. (author)

  18. CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth.

    Science.gov (United States)

    Golubovskaya, Vita; Berahovich, Robert; Zhou, Hua; Xu, Shirley; Harto, Hizkia; Li, Le; Chao, Cheng-Chi; Mao, Mike Ming; Wu, Lijun

    2017-10-21

    CD47 is a glycoprotein of the immunoglobulin superfamily that is often overexpressed in different types of hematological and solid cancer tumors and plays important role in blocking phagocytosis, increased tumor survival, metastasis and angiogenesis. In the present report, we designed CAR (chimeric antigen receptor)-T cells that bind CD47 antigen. We used ScFv (single chain variable fragment) from mouse CD47 antibody to generate CD47-CAR-T cells for targeting different cancer cell lines. CD47-CAR-T cells effectively killed ovarian, pancreatic and other cancer cells and produced high level of cytokines that correlated with expression of CD47 antigen. In addition, CD47-CAR-T cells significantly blocked BxPC3 pancreatic xenograft tumor growth after intratumoral injection into NSG mice. Moreover, we humanized mouse CD47 ScFv and showed that it effectively bound CD47 antigen. The humanized CD47-CAR-T cells also specifically killed ovarian, pancreatic, and cervical cancer cell lines and produced IL-2 that correlated with expression of CD47. Thus, CD47-CAR-T cells can be used as a novel cellular therapeutic agent for treating different types of cancer.

  19. Self-assembly morphology effects on the crystallization of semicrystalline block copolymer thin film

    Science.gov (United States)

    Wei, Yuhan; Pan, Caiyuan; Li, Binyao; Han, Yanchun

    2007-03-01

    Self-assembly morphology effects on the crystalline behavior of asymmetric semicrystalline block copolymer polystyrene-block-poly(L-lactic acid) thin film were investigated. Firstly, a series of distinctive self-assembly aggregates, from spherical to ellipsoid and rhombic lamellar micelles (two different kinds of rhombic micelles, defined as rhomb 1 and rhomb 2) was prepared by means of promoting the solvent selectivity. Then, the effects of these self-assembly aggregates on crystallization at the early stage of film evolution were investigated by in situ hot stage atomic force microscopy. Heterogeneous nucleation initiated from the spherical micelles and dendrites with flat on crystals appeared with increasing temperature. At high temperature, protruding structures were observed due to the thickening of the flat-on crystals and finally more thermodynamically stable crystallization formed. Annealing the rhombic lamellar micelles resulted in different phenomena. Turtle-shell-like crystalline structure initiated from the periphery of the rhombic micelle 1 and spread over the whole film surface in the presence of mostly noncrystalline domain interior. Erosion and small hole appeared at the surface of the rhombic lamellar micelle 2; no crystallization like that in rhomb 1 occurred. It indicated that the chain-folding degree was different in these two micelles, which resulted in different annealing behaviors.

  20. Pressor effect for ethanol and absence of its. cap alpha. -blocking activity in the SHR

    Energy Technology Data Exchange (ETDEWEB)

    Abdel-Rahman, A.R.A.; Iams, S.G.; Wooles, V.R.

    1986-03-01

    In a previous study the authors have suggested ethanol (ETOH) has an ..cap alpha..-blocking activity in anesthetized Sprague Dawley (SD) rats. The present investigation shows that ETOH (1 g/Kg, i.v.) has a pressor and tachycardic effect in SHR, SD and Wistar Kyoto (WKY) rats. However, quantitative differences existed between ..delta.. MAP, but not ..delta.. HR, among the 3 strains; the biggest rise occurred in the SHR and the least in SD. It is not yet clear whether the significantly higher MAP in the SHR contributes to the significantly larger ..delta.. MAP in response to ETOH. Nonetheless, MAP was similar in WKY and SD in spite of a larger ..delta.. MAP after ETOH in the former. Furthermore, both SD and WKY rats showed a significant and parallel rightward shift of the phenylephrine (PE) pressor response curve after ETOH (more in SD than WKY) suggesting an ..cap alpha..-blocking activity for ethanol and confirming their previous findings in SD rats. This suggestion was further supported by the absence of any shift in the angiotensin II (AII) dose-response curves. On the other hand, neither PE nor AII pressor responsiveness was influenced by ETOH in the SHR suggesting an absence of ..cap alpha..-blocking activity for ETOH in this strain. Finally, no change occurred in the baroreflex control of HR in SHR as compared to an impairment of this function in WKY and SD rats. This may relate at least in part, to the already depressed baroreflex function in the SHR.

  1. Effects of arthroscopy-guided suprascapular nerve block combined with ultrasound-guided interscalene brachial plexus block for arthroscopic rotator cuff repair: a randomized controlled trial.

    Science.gov (United States)

    Lee, Jae Jun; Hwang, Jung-Taek; Kim, Do-Young; Lee, Sang-Soo; Hwang, Sung Mi; Lee, Na Rea; Kwak, Byung-Chan

    2017-07-01

    The aim of this study was to compare the pain relieving effect of ultrasound-guided interscalene brachial plexus block (ISB) combined with arthroscopy-guided suprascapular nerve block (SSNB) with that of ultrasound-guided ISB alone within the first 48 h after arthroscopic rotator cuff repair. Forty-eight patients with rotator cuff tears who had undergone arthroscopic rotator cuff repair were enrolled. The 24 patients in group 1 received ultrasound-guided ISB and arthroscopy-guided SSNB; the remaining 24 patients in group 2 underwent ultrasound-guided ISB alone. Visual analogue scale pain score and patient satisfaction score were checked at 1, 3, 6, 12, 18, 24, and 48 h post-operatively. Group 1 had a lower visual analogue scale pain score at 3, 6, 12, 18, 24, and 48 h post-operatively (1.7  6.0, 6.2 > 4.3, 6.4 > 5.1, 6.9 > 5.9, 7.9 > 7.1). Six patients in group 1 developed rebound pain twice, and the others in group 1 developed it once. All of the patients in group 2 had one rebound phenomenon each (p = 0.010). The mean timing of rebound pain in group 1 was later than that in group 2 (15.5 > 9.3 h, p  4.0, p = 0.001). Arthroscopy-guided SSNB combined with ultrasound-guided ISB resulted in lower visual analogue scale pain scores at 3-24 and 48 h post-operatively, and higher patient satisfaction scores at 6-36 h post-operatively with the attenuated rebound pain compared to scores in patients who received ultrasound-guided ISB alone after arthroscopic rotator cuff repair. The combined blocks may relieve post-operative pain more effectively than the single block within 48 h after arthroscopic cuff repair. Randomized controlled trial, Level I. ClinicalTrials.gov Identifier: NCT02424630.

  2. Thermal Bridge Effect of Aerated Concrete Block Wall in Cold Regions

    Science.gov (United States)

    Li, Baochang; Guo, Lirong; Li, Yubao; Zhang, Tiantian; Tan, Yufei

    2018-01-01

    As a self-insulating building material which can meet the 65 percent energy-efficiency requirements in cold region of China, aerated concrete blocks often go moldy, frost heaving, or cause plaster layer hollowing at thermal bridge parts in the extremely cold regions due to the restrictions of environmental climate and construction technique. L-shaped part and T-shaped part of aerated concrete walls are the most easily influenced parts by thermal bridge effect. In this paper, a field test is performed to investigate the scope of the thermal bridge effect. Moreover, a heat transfer calculation model for L-shaped wall and T-shaped wall is developed. According to the simulation results, the temperature fields of the thermal bridge affected regions are simulated and analyzed. The research outputs can provide theoretical basis for the application of aerated concrete wall in extremely cold regions.

  3. Effects of 252Cf neutrons, transmitted through an iron block on human lymphocyte chromosome

    International Nuclear Information System (INIS)

    Tanaka, K.; Hoshi, M.; Sawada, S.; Kamada, N.

    1994-01-01

    Chromosome aberration of human peripheral blood lymphocytes exposed to californium-252 ( 252 Cf) neutrons transmitted through a 15 cm thick iron block was analysed. The spectrum of the filtered neutrons ranged from 0.1 to 2MeV with a peak at 0.7 MeV, simulating the Hiroshima atomic bomb neutron spectrum as shown in the Dosimetry System 1986 (DS86). Chromosome aberration frequencies after exposure to filtered and unfiltered 252 Cf radiation were compared. Acentric ring chromosomes were significantly increased (p 0.1). The relative biological effectiveness (RBE) of the neutrons with respect to the formation of dicentrics and centric rings was 10.9 and 12.3 in the filtered and unfiltered conditions respectively, but the difference was not statistically significant. These results provide useful information for the re-evaluation of the biological effect of the Hiroshima atomic bomb radiations. (Author)

  4. Evaluation of effectiveness of stellate ganglion block (SGB) treatment of sudden hearing loss.

    Science.gov (United States)

    Takinami, Yoshikazu

    2012-01-01

    A stellate ganglion block (SGB) based on the goal of improving internal ear circulatory disturbance appears to be beneficial for the treatment of sudden hearing loss. To evaluate the effectiveness of SGB for sudden hearing loss. This retrospective study reviewed the medical records of 49 patients who received SGBs and 496 patients who received only conservative therapy, primarily with systemic steroids, for treatment of sudden hearing loss. Propensity scores were used in pairwise matching of these patients to avoid selection biases between the two treatment modalities. Propensity score matching yielded 48 pairs. The mean therapeutic effect of the SGB was calculated to be 0.40 ± 0.20 (mean ± standard error, p = 0.051).

  5. The role of NMDA receptors of the medial septum and dorsal hippocampus on memory acquisition.

    Science.gov (United States)

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

    2016-04-01

    The glutamatergic neurons in the medial septal/diagonal band of broca (MS/DB) affect the hippocampal functions by modulating the septo-hippocampal neurons. Our study investigated the possible role of NMDA receptors of the medial septum nucleus (MS) and dorsal hippocampus (CA1) on memory acquisition in male Wistar rats. Animals were bilaterally implanted with chronic cannulae in the MS and CA1. Rats were trained in a step-through type inhibitory avoidance task, and tested 24h after training to measure step-through latency as memory retrieval. Our results indicated that pre-training intra-MS or intra-CA1 infusions of NMDA (0.125 μg/rat) and D-AP7 (0.012 μg/rat) increased and decreased memory acquisition, respectively when compared to saline control group. Also, pre-training intra-CA1 and intra-MS injection of an effect dose of D-AP7 (0.012 μg/rat) along with an effect dose of NMDA (0.125 μg/rat) impaired memory acquisition. Interestingly, pre-training intra-CA1/MS infusion of D-AP7 (0.012 μg/rat) diminished memory response produced by pre-training injection of NMDA (0.125 μg/rat) in the MS/CA1, respectively (cross injection or bilateral injection). Also, all above doses of drugs did not alter locomotor activity. These results suggest that the glutamatergic pathway between the MS and CA1 regions is involved in memory acquisition process. Copyright © 2016. Published by Elsevier Inc.

  6. The Effect of Blocked, Random and Mixed Practice Schedules on Speech Motor Learning of Tongue Twisters in Unimpaired Speakers.

    Science.gov (United States)

    Jones, Kelly; Croot, Karen

    2016-10-01

    There are few investigations comparing practice schedules in speech motor learning, despite certain schedules being recommended for the clinical treatment of speech motor disorders. This study compared effects of random, blocked and mixed practice on tongue twister accuracy in unimpaired speakers. We hypothesized that blocked practice would benefit acquisition of learning, but that random practice and mixed blocked-then-random practice would yield superior retention of learning. We found that the random and blocked-random practice schedules yielded superior accuracy at the end of the acquisition phase of learning and at a 1-week retention test. Exploratory post hoc analyses raised the possibility that the retention effects were most evident when tongue twisters were elicited in a random schedule. Theoretical accounts of these results are discussed.

  7. Prospective randomized trial to evaluate effectiveness of periprostatic nerve block in prostatic biopsy

    Directory of Open Access Journals (Sweden)

    P Lavania

    2006-01-01

    Full Text Available Objectives: The objective of the study was to evaluate the efficacy of local anesthetic infiltration, in decreasing the discomfort experienced by patients undergoing trans-rectal ultrasound (TRUS guided biopsy of prostate. Materials and methods: Between January 2002 and February 2003, we investigated consecutively, asymptomatic men, suspected of having prostatic cancer. About 39 patients were randomized to receive 10 ml of 2% Lidocaine periprostatic block + intrarectal Lidocaine gel (group 1 = 20, or intarectal Lidocaine gel only (group 2 = 19 during prostatic biopsy. Immediately following the TRUS-guided biopsy, patients were asked to grade the pain they experienced using the 11-point visual analogue score (VAS. Results: The mean pain score in the patients of group 1 were significantly lower than the patients of group 2 ( P < 0.001, suggesting that periprostatic block produced a significant reduction in the perceived pain. Conclusions: Local anesthetic infiltration by TRUS-guided injection of Lidocaine is effective for decreasing pain associated with prostatic biopsy.

  8. The effect of glazing and aging on the surface properties of CAD/CAM resin blocks.

    Science.gov (United States)

    Tekçe, Neslihan; Fidan, Sinan; Tuncer, Safa; Kara, Dilan; Demirci, Mustafa

    2018-02-01

    To investigate the effect of accelerated aging on surface properties of glazed CAD/CAM resin blocks using a 2D surface profilometer and a 3D non-contact optical profilometer. Three types of CAD/CAM resin restorative materials, LAVA Ultimate (3M ESPE, St Paul, MN, USA), VITA Enamic (Vita Zahnfabrik H. Rauter, Bad Säckingen, Germany), and Cerasmart (GC Corparation, Tokyo, Japan) were used for this study. CAD/CAM blocks were cut in 3-mm thickness slabs and divided into three groups; Group 1: control group (specimens polished with 600 grit SCI paper); Group 2: specimens sandblasted, silanized, and glazed with Optiglaze Color (GC); Group 3: glazed specimens subjected to 5000 thermocycles (n=15). The surface roughness (R a and R z ) was evaluated using a profilometer and a 3D scanning instrument. Data were analyzed using two-way ANOVA and Tukey's post-hoc test ( P .05). For VITA and Cerasmart, the specimens in Group 1 exhibited significantly higher R a values than Group 2 ( P .05). Glaze material Optiglaze Color makes CAD/CAM resin surfaces smooth and glazed CAD/CAM surfaces seem resistant to deterioration under 5000 thermocycles.

  9. A randomized placebo-controlled trial of an NMDA receptor antagonist in sleep-disordered breathing.

    Science.gov (United States)

    Torvaldsson, Stefan; Grote, Ludger; Peker, Yüksel; Basun, Hans; Hedner, Jan

    2005-06-01

    Hypoxemia is a powerful stimulus of glutamate release in the central nervous system (CNS) and a hallmark phenomenon in sleep disordered breathing (SDB). Glutamate effects that include neuronal damage and apoptosis following hypoxemia and apnea following microinjections in animal models are in part mediated via postjunctional N-methyl-D-aspartate (NMDA) receptors. This was a double blind, randomized, placebo-controlled single dose cross-over study of the NMDA receptor antagonist AR-R15896AR in 15 male patients with moderate to severe SDB. Seven patients received 120 mg and eight patients received 350 mg AR-R15896AR or corresponding placebo (given by 2 h infusion) starting half an hour before estimated sleep onset. AR-R15896AR concentrations were in line with the predicting kinetic model. A standard polysomnographic montage was applied. Repeated plasma samples were obtained in nine patients for analysis of plasma glutamate. Glutamate concentration in plasma did not change overnight and was unrelated to severity of SDB. Overall AHI (apnea-hypopnea index; primary efficacy variable) or investigated oxygen saturation variables were not significantly changed after AR-R15896AR at either dosage level. Side effects were mostly confined to the higher dose level and included vivid dreams, nightmares as well as in two cases mild hallucinations. The previously postulated role of glutamate in SDB could not be confirmed after AR-R15896AR induced NMDA-receptor blockade.

  10. Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons

    KAUST Repository

    Yang, Jiangyan

    2014-07-28

    L-lactate is a product of aerobic glycolysis that can be used by neurons as an energy substrate. Here we report that in neurons L-lactate stimulates the expression of synaptic plasticity-related genes such as Arc, c-Fos, and Zif268 through a mechanism involving NMDA receptor activity and its downstream signaling cascade Erk1/2. L-lactate potentiates NMDA receptor-mediated currents and the ensuing increase in intracellular calcium. In parallel to this, L-lactate increases intracellular levels of NADH, thereby modulating the redox state of neurons. NADH mimics all of the effects of L-lactate on NMDA signaling, pointing to NADH increase as a primary mediator of L-lactate effects. The induction of plasticity genes is observed both in mouse primary neurons in culture and in vivo in the mouse sensory-motor cortex. These results provide insights for the understanding of the molecular mechanisms underlying the critical role of astrocyte-derived L-lactate in long-term memory and long-term potentiation in vivo. This set of data reveals a previously unidentified action of L-lactate as a signaling molecule for neuronal plasticity.

  11. NMDA Receptor Antagonist Ketamine Distorts Object Recognition by Reducing Feedback to Early Visual Cortex.

    Science.gov (United States)

    van Loon, Anouk M; Fahrenfort, Johannes J; van der Velde, Bauke; Lirk, Philipp B; Vulink, Nienke C C; Hollmann, Markus W; Scholte, H Steven; Lamme, Victor A F

    2016-05-01

    It is a well-established fact that top-down processes influence neural representations in lower-level visual areas. Electrophysiological recordings in monkeys as well as theoretical models suggest that these top-down processes depend on NMDA receptor functioning. However, this underlying neural mechanism has not been tested in humans. We used fMRI multivoxel pattern analysis to compare the neural representations of ambiguous Mooney images before and after they were recognized with their unambiguous grayscale version. Additionally, we administered ketamine, an NMDA receptor antagonist, to interfere with this process. Our results demonstrate that after recognition, the pattern of brain activation elicited by a Mooney image is more similar to that of its easily recognizable grayscale version than to the pattern evoked by the identical Mooney image before recognition. Moreover, recognition of Mooney images decreased mean response; however, neural representations of separate images became more dissimilar. So from the neural perspective, unrecognizable Mooney images all "look the same", whereas recognized Mooneys look different. We observed these effects in posterior fusiform part of lateral occipital cortex and in early visual cortex. Ketamine distorted these effects of recognition, but in early visual cortex only. This suggests that top-down processes from higher- to lower-level visual areas might operate via an NMDA pathway. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Lipid raft integrity affects GABAA receptor, but not NMDA receptor modulation by psychopharmacological compounds.

    Science.gov (United States)

    Nothdurfter, Caroline; Tanasic, Sascha; Di Benedetto, Barbara; Uhr, Manfred; Wagner, Eva-Maria; Gilling, Kate E; Parsons, Chris G; Rein, Theo; Holsboer, Florian; Rupprecht, Rainer; Rammes, Gerhard

    2013-07-01

    Lipid rafts have been shown to play an important role for G-protein mediated signal transduction and the function of ligand-gated ion channels including their modulation by psychopharmacological compounds. In this study, we investigated the functional significance of the membrane distribution of NMDA and GABAA receptor subunits in relation to the accumulation of the tricyclic antidepressant desipramine (DMI) and the benzodiazepine diazepam (Diaz). In the presence of Triton X-100, which allowed proper separation of the lipid raft marker proteins caveolin-1 and flotillin-1 from the transferrin receptor, all receptor subunits were shifted to the non-raft fractions. In contrast, under detergent-free conditions, NMDA and GABAA receptor subunits were detected both in raft and non-raft fractions. Diaz was enriched in non-raft fractions without Triton X-100 in contrast to DMI, which preferentially accumulated in lipid rafts. Impairment of lipid raft integrity by methyl-β-cyclodextrine (MβCD)-induced cholesterol depletion did not change the inhibitory effect of DMI at the NMDA receptor, whereas it enhanced the potentiating effect of Diaz at the GABAA receptor at non-saturating concentrations of GABA. These results support the hypothesis that the interaction of benzodiazepines with the GABAA receptor likely occurs outside of lipid rafts while the antidepressant DMI acts on ionotropic receptors both within and outside these membrane microdomains.

  13. Which one is more effective for analgesia in infratentorial craniotomy? The scalp block or local anesthetic infiltration.

    Science.gov (United States)

    Akcil, Eren Fatma; Dilmen, Ozlem Korkmaz; Vehid, Hayriye; Ibısoglu, Lutfiye Serap; Tunali, Yusuf

    2017-03-01

    The most painful stages of craniotomy are the placement of the pin head holder and the skin incision. The primary aim of the present study is to compare the effects of the scalp block and the local anesthetic infiltration with bupivacaine 0.5% on the hemodynamic response during the pin head holder application and the skin incision in infratentorial craniotomies. The secondary aims are the effects on pain scores and morphine consumption during the postoperative 24h. This prospective, randomized and placebo controlled study included forty seven patients (ASA I, II and III). The scalp block was performed in the Group S, the local anesthetic infiltration was performed in the Group I and the control group (Group C) only received remifentanil as an analgesic during the intraoperative period. The hemodynamic response to the pin head holder application and the skin incision, as well as postoperative pain intensity, cumulative morphine consumption and opioid related side effects were compared. The scalp block reduced the hemodynamic response to the pin head holder application and the skin incision in infratentorial craniotomies. The local anesthetic infiltration reduced the hemodynamic response to the skin incision. As well as both scalp block and local anesthetic infiltration reduced the cumulative morphine consumption in postoperative 24h. Moreover, the pain intensity was lower after scalp block in the early postoperative period. The scalp block may provide better analgesia in infratentorial craniotomies than local anesthetic infiltration. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Effect of block composition on thermal properties and melt viscosity of poly[2-(dimethylaminoethyl methacrylate], poly(ethylene oxide and poly(propylene oxide block co-polymers

    Directory of Open Access Journals (Sweden)

    2011-09-01

    Full Text Available To modify the rheological properties of certain commercial polymers, a set of block copolymers were synthesized through oxyanionic polymerization of 2-(dimethylaminoethyl methacrylate to the chain ends of commercial prepolymers, namely poly(ethylene oxide (PEO, poly(ethylene oxide-block-poly(propylene oxide-block-poly(ethylene oxide (PEO-PPO-PEO, and poly(propylene oxide (PPO. The formed block copolymers were analysed with size exclusion chromatography and nuclear magnetic resonance spectroscopy in order to confirm block formation. Thermal characterization of the resulting polymers was done with differential scanning calorimetry. Thermal transition points were also confirmed with rotational rheometry, which was primarily used to measure melt strength properties of the resulting block co-polymers. It was observed that the synthesised poly[2-(dimethylaminoethyl methacrylate]-block (PDM affected slightly the thermal transition points of crystalline PEO-block but the influence was stronger on amorphous PPO-blocks. Frequency sweeps measured above the melting temperatures for the materials confirmed that the pre-polymers (PEO and PEO-PPO-PEO behave as Newtonian fluids whereas polymers with a PDM block structure exhibit clear shear thinning behaviour. In addition, the PDM block increased the melt viscosity when compared with that one of the pre-polymer. As a final result, it became obvious that pre-polymers modified with PDM were in entangled form, in the melted state as well in the solidified form.

  15. Involvement of hippocampal NMDA receptors in retention of shuttle avoidance conditioning in rats

    Directory of Open Access Journals (Sweden)

    Roesler R.

    1998-01-01

    Full Text Available The purpose of this research was to evaluate the role of hippocampal N-methyl-D-aspartate (NMDA receptors in acquisition and consolidation of memory during shuttle avoidance conditioning in rats. Adult male Wistar rats were surgically implanted with cannulae aimed at the CA1 area of the dorsal hippocampus. After recovery from surgery, animals were trained and tested in a shuttle avoidance apparatus (30 trials, 0.5-mA footshock, 24-h training-test interval. Immediately before or immediately after training, animals received a bilateral intrahippocampal 0.5-µl infusion containing 5.0 µg of the NMDA competitive receptor antagonist aminophosphonopentanoic acid (AP5 or vehicle (phosphate-buffered saline, pH 7.4. Infusion duration was 2 min per side. Pre-training infusion of AP5 impaired retention test performance (mean ± SEM number of conditioned responses (CRs during retention test session was 16.47 ± 1.78 in the vehicle group and 9.93 ± 1.59 in the AP5 group; P<0.05. Post-training infusion of AP5 did not affect retention (mean ± SEM number of conditioned responses during retention test session was 18.46 ± 1.94 in the vehicle group and 20.42 ± 2.38 in the AP5 group; P>0.10. This impairment could not be attributed to an effect on acquisition, motor activity or footshock sensitivity since AP5 affected neither training session performance measured by the number of CRs nor the number of intertrial crossings during the training session. These data suggest that NMDA receptors in the hippocampus are critical for retention of shuttle avoidance conditioning, in agreement with previous evidence showing a role of NMDA receptors in fear memory.

  16. Comparison of the effect of land-sea thermal contrast on interdecadal variations in winter and summer blockings

    Science.gov (United States)

    He, Yongli; Huang, Jianping; Li, Dongdong; Xie, Yongkun; Zhang, Guolong; Qi, Yulei; Wang, Shanshan; Totz, Sonja

    2017-11-01

    The influence of winter and summer land-sea surface thermal contrast on blocking for 1948-2013 is investigated using observations and the coupled model intercomparison project outputs. The land-sea index (LSI) is defined to measure the changes of zonal asymmetric thermal forcing under global warming. The summer LSI shows a slower increasing trend than winter during this period. For the positive of summer LSI, the EP flux convergence induced by the land-sea thermal forcing in the high latitude becomes weaker than normal, which induces positive anomaly of zonal-mean westerly and double-jet structure. Based on the quasiresonance amplification mechanism, the narrow and reduced westerly tunnel between two jet centers provides a favor environment for more frequent blocking. Composite analysis demonstrates that summer blocking shows an increasing trend of event numbers and a decreasing trend of durations. The numbers of the short-lived blocking persisting for 5-9 days significantly increases and the numbers of the long-lived blocking persisting for longer than 10 days has a weak increase than that in negative phase of summer LSI. The increasing transient wave activities induced by summer LSI is responsible for the decreasing duration of blockings. The increasing blocking due to summer LSI can further strengthen the continent warming and increase the summer LSI, which forms a positive feedback. The opposite dynamical effect of LSI on summer and winter blocking are discussed and found that the LSI-blocking negative feedback partially reduces the influence of the above positive feedback and induce the weak summer warming rate.

  17. Stress-induced changes of hippocampal NMDA receptors: modulation by duloxetine treatment.

    Directory of Open Access Journals (Sweden)

    Francesca Calabrese

    Full Text Available It is now well established that the glutamatergic system contributes to the pathophysiology of depression. Exposure to stress, a major precipitating factor for depression, enhances glutamate release that can contribute to structural abnormalities observed in the brain of depressed subjects. On the other hand, it has been demonstrated that NMDA antagonists, like ketamine, exert an antidepressant effect at preclinical and clinical levels. On these bases, the purpose of our study was to investigate whether chronic mild stress is associated with specific alterations of the NMDA receptor complex, in adult rats, and to establish whether concomitant antidepressant treatment could normalize such deficits. We found that chronic stress increases the expression of the obligatory GluN1 subunit, as well as of the accessory subunits GluN2A and GluN2B at transcriptional and translational levels, particularly in the ventral hippocampus. Concomitant treatment with the antidepressant duloxetine was able to normalize the increase of glutamatergic receptor subunit expression, and correct the changes in receptor phosphorylation produced by stress exposure. Our data suggest that prolonged stress, a condition that has etiologic relevance for depression, may enhance glutamate activity through post-synaptic mechanisms, by regulating NMDA receptors, and that antidepressants may in part normalize such changes. Our results provide support to the notion that antidepressants may exert their activity in the long-term also via modulation of the glutamatergic synapse.

  18. Non-Local Spin Blocking Effect of Zero-Energy Majorana Fermions

    Science.gov (United States)

    Ren, Chongdan; Yang, Jianglan; Xiang, Jin; Wang, Sake; Tian, Hongyu

    2017-12-01

    One of the fascinating properties of a pair of spatially separated Majorana Fermions emerged in solid state materials is their inherent non-locality. We consider two half metals coupled to a one-dimensional finite-length topological superconductor. We find that zero-energy Majorana Fermions (ZMFs) induce a striking non-local spin-blocking effect, in which the one side tunneling process is affected by the spin polarization of the other side ZMF, similar to the electron teleportation phenomena reported by Fu [https://doi.org/10.1103/PhysRevLett.104.056402" xlink:type="simple">Phys. Rev. Lett. 104, 056402 (2010)]. In contrast, for non-zero-energy Majorana Fermions (NMFs), the right and left spin-relating tunneling processes are completely independent. These findings reveal that, for uncoupled but paired ZMFs, there exists cross-correlation between the tunneling events. Our finding may provide some new insight into identify Majorana Fermions.

  19. Effect of adductor canal block on pain in patients with severe pain after total knee arthroplasty

    DEFF Research Database (Denmark)

    Grevstad, Jens Ulrik; Mathiesen, Ole; Lind, T

    2014-01-01

    BACKGROUND: Total knee arthroplasty (TKA) is associated with varying degrees of pain. A considerable proportion (25-40%) of patients experience severe pain, despite a comprehensive multimodal analgesic regimen. We hypothesized that adductor canal block (ACB) would reduce pain in this patient...... category compared with placebo. METHODS: Fifty patients with severe pain, defined as having a visual analogue scale (VAS) pain score of >60 during active flexion of the knee on the first or the second postoperative day after TKA, were included in this randomized, double-blind, placebo-controlled trial. All......% of the patients had no effect during active flexion. At rest, however, only 8% had more than mild pain after ACB compared with 57% at inclusion. CONCLUSIONS: ACB reduced VAS with 32 mm, during active flexion of the knee, in patients with severe pain after TKA, but a large proportion (78%) still had at least...

  20. Mechanical behavior analysis of small-scale modeling of ceramic block masonry structures: geometries effect

    Directory of Open Access Journals (Sweden)

    E. Rizzatti

    Full Text Available This paper presents the experimental results of a research program with ceramic block masonry under compression. Four different block geometries were investigated. Two of them had circular hollows with different net area. The third one had two rectangular hollow and the last block was with rectangular hollows and a double central webs. The prisms and walls were built with two mortar type 1:1:6 (I and 1:0,5:4 (II (proportions by volume of cement: lime: sand. One:three small scale blocks were used to test block, prisms and walls on compression. It was possible to conclude that the block with double central webs gave better results of compressive strength showing to be more efficient. The mortar didn't influenced the compressive strength of prisms and walls.

  1. Functional neurokinin and NMDA receptor activity in an animal naturally lacking substance P: the naked mole-rat.

    Directory of Open Access Journals (Sweden)

    Antje Brand

    Full Text Available Naked mole-rats are extremely unusual among mammals in that their cutaneous C-fibers lack the neuropeptide Substance P (SP. In other mammals, SP plays an important role in nociception: it is released from C-fibers onto spinal neurons where it facilitates NMDA receptor activity and causes sensitization that can last for minutes, hours or days. In the present study, we tested the effects of intrathecal application of: 1 SP, 2 an SP antagonist (GR-82334, and 3 an NMDA antagonist (APV on heat-evoked foot withdrawal. In the naked mole-rat, at a high enough concentration, application of SP caused a large, immediate, and long-lasting sensitization of foot withdrawal latency that was transiently reversed by application of either antagonist. However, neither SP nor NMDA antagonists had an effect when administered alone to naïve animals. In contrast, both antagonists induced an increase in basal withdrawal latency in mice. These results indicate that spinal neurons in naked mole-rats have functional SP and NMDA receptors, but that these receptors do not participate in heat-evoked foot withdrawal unless SP is experimentally introduced. We propose that the natural lack of SP in naked mole-rat C-fibers may have resulted during adaptation to living in a chronically high carbon dioxide, high ammonia environment that, in other mammals, would stimulate C-fibers and evoke nocifensive behavior.

  2. Functional neurokinin and NMDA receptor activity in an animal naturally lacking substance P: the naked mole-rat.

    Science.gov (United States)

    Brand, Antje; Smith, Ewan St J; Lewin, Gary R; Park, Thomas J

    2010-12-21

    Naked mole-rats are extremely unusual among mammals in that their cutaneous C-fibers lack the neuropeptide Substance P (SP). In other mammals, SP plays an important role in nociception: it is released from C-fibers onto spinal neurons where it facilitates NMDA receptor activity and causes sensitization that can last for minutes, hours or days. In the present study, we tested the effects of intrathecal application of: 1) SP, 2) an SP antagonist (GR-82334), and 3) an NMDA antagonist (APV) on heat-evoked foot withdrawal. In the naked mole-rat, at a high enough concentration, application of SP caused a large, immediate, and long-lasting sensitization of foot withdrawal latency that was transiently reversed by application of either antagonist. However, neither SP nor NMDA antagonists had an effect when administered alone to naïve animals. In contrast, both antagonists induced an increase in basal withdrawal latency in mice. These results indicate that spinal neurons in naked mole-rats have functional SP and NMDA receptors, but that these receptors do not participate in heat-evoked foot withdrawal unless SP is experimentally introduced. We propose that the natural lack of SP in naked mole-rat C-fibers may have resulted during adaptation to living in a chronically high carbon dioxide, high ammonia environment that, in other mammals, would stimulate C-fibers and evoke nocifensive behavior.

  3. Humanin rescues cultured rat cortical neurons from NMDA-induced toxicity through the alleviation of mitochondrial dysfunction.

    Science.gov (United States)

    Cui, Ai-Ling; Zhang, Ying-Hua; Li, Jian-Zhong; Song, Tianbin; Liu, Xue-Min; Wang, Hui; Zhang, Ce; Ma, Guo-Lin; Zhang, Hui; Li, Kefeng

    2017-01-01

    N -methyl-D-aspartate (NDMA) receptor-mediated excitotoxicity has been implicated in a variety of pathological situations such as Alzheimer's disease (AD) and Parkinson's disease. However, no effective treatments for the same have been developed so far. Humanin (HN) is a 24-amino acid peptide originally cloned from the brain of patients with AD and it prevents stress-induced cell death in many cells/tissues. In our previous study, HN was found to effectively rescue rat cortical neurons. It is still not clear whether HN protects the neurons through the attenuation of mitochondrial dysfunction. In this study, excitatory toxicity was induced by NMDA, which binds the NMDA receptor in primarily cultured rat cortical neurons. We found that NMDA (100 μmol/L) dramatically induced the decrease of cell viability and caused mitochondrial dysfunction. Pretreatment of the neurons with HN (1 μmol/L) led to significant increases of mitochondrial succinate dehydrogenase (SDH) activity and membrane potential. In addition, HN pretreatment significantly reduced the excessive production of both reactive oxygen species (ROS) and nitric oxide (NO). Thus, HN could attenuate the excitotoxicity caused by the overactivation of the NMDA receptor through the alleviation of mitochondrial dysfunction.

  4. Effect of sympathetic nerve block on acute inflammatory pain and hyperalgesia

    DEFF Research Database (Denmark)

    Pedersen, J L; Rung, G W; Kehlet, H

    1997-01-01

    . The duration and quality of blocks were evaluated by the sympatogalvanic skin response and skin temperature. Bilateral heat injuries were produced on the medial surfaces of the calves with a 50 x 25 mm thermode (47 degrees C, 7 min) 45 min after the blocks. Pain intensity induced by heat, pain thresholds....... METHODS: The study was made as a randomized, single blinded investigation, in which the volunteers served as their own controls. A lumbar sympathetic nerve block and a contralateral placebo block were performed in 24 persons by injecting 10 ml bupivacaine (0.5%) and 10 ml saline, respectively...... acute inflammatory pain or hyperalgesia after a heat injury in human skin....

  5. Effect of Epidural Block under General Anesthesia on Pulse Transit Time

    International Nuclear Information System (INIS)

    Choi, Byeong Cheol; Kim, Seong Min; Jung, Dong Keun; Kim, Gi Ryon; Lee, He Jeong; Jeon, Gye Rock

    2005-01-01

    Epidural block under general anesthesia has been widely used to control postoperative pain. In this anesthetic state many hemodynamic parameters are changed. Moreover pulse transit time is influenced by this memodynamic change. PPT change in the finger and the toe due to relaxation of arterial wall muscle after general anesthesia and epidural block under general anesthesia. This study, in the both general anesthesia and epidural block under general anesthesia, ΔPTT of the toe and of the finger are measured. In addition, ΔPTT(toe-finger) of the epidural block under general anesthesia and of the general anesthesia were compared

  6. Effect of preemptive nerve block on inflammation and hyperalgesia after human thermal injury

    DEFF Research Database (Denmark)

    Pedersen, J L; Crawford, M E; Dahl, J B

    1996-01-01

    compared to the opposite unblocked leg for 12 h after bilateral thermal injuries (15 x 25 mm, 49 degrees C for 5 min) in 20 healthy volunteers. Recovery from the block was identified by return of sensation to cold. RESULTS: Six subjects were excluded because of insufficient initial block (2 subjects......) or because the block lasted beyond the study period (4 subjects). The remaining 14 subjects experienced significantly reduced primary (P = 0.005) and secondary hyperplasia (P = 0.01) in the blocked leg after return of cold sensation compared to the unblocked leg. Erythema intensity and blister formation were...

  7. The role of GluN2B-containing NMDA receptors in short- and long-term fear recall.

    Science.gov (United States)

    Mikics, Eva; Toth, Mate; Biro, Laszlo; Bruzsik, Biborka; Nagy, Boglarka; Haller, Jozsef

    2017-08-01

    N-methyl-d-aspartate (NMDA) receptors are crucial synaptic elements in long-term memory formation, including the associative learning of fearful events. Although NMDA blockers were consistently shown to inhibit fear memory acquisition and recall, the clinical use of general NMDA blockers is hampered by their side effects. Recent studies revealed significant heterogeneity in the distribution and neurophysiological characteristics of NMDA receptors with different GluN2 (NR2) subunit composition, which may have differential role in fear learning and recall. To investigate the specific role of NMDA receptor subpopulations with different GluN2 subunit compositions in the formation of lasting traumatic memories, we contrasted the effects of general NMDA receptor blockade with GluN2A-, GluN2B-, and GluN2C/D subunit selective antagonists (MK-801, PEAQX, Ro25-6981, PPDA, respectively). To investigate acute and lasting consequences, behavioral responses were investigated 1 and 28days after fear conditioning. We found that MK-801 (0.05 and 0.1mg/kg) decreased fear recall at both time points. GluN2B receptor subunit blockade produced highly similar effects, albeit efficacy was somewhat smaller 28days after fear conditioning. Unlike MK-801, Ro25-6981 (3 and 10mg/kg) did not affect locomotor activity in the open-field. In contrast, GluN2A and GluN2C/D blockers (6 and 20mg/kg PEAQX; 3 and 10mg/kg PPDA, respectively) had no effect on conditioned fear recall at any time point and dose. This sharp contrast between GluN2B- and other subunit-containing NMDA receptor function indicates that GluN2B receptor subunits are intimately involved in fear memory formation, and may provide a novel pharmacological target in post-traumatic stress disorder or other fear-related disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Computationally Discovered Potentiating Role of Glycans on NMDA Receptors

    Science.gov (United States)

    Sinitskiy, Anton V.; Stanley, Nathaniel H.; Hackos, David H.; Hanson, Jesse E.; Sellers, Benjamin D.; Pande, Vijay S.

    2017-04-01

    N-methyl-D-aspartate receptors (NMDARs) are glycoproteins in the brain central to learning and memory. The effects of glycosylation on the structure and dynamics of NMDARs are largely unknown. In this work, we use extensive molecular dynamics simulations of GluN1 and GluN2B ligand binding domains (LBDs) of NMDARs to investigate these effects. Our simulations predict that intra-domain interactions involving the glycan attached to residue GluN1-N440 stabilize closed-clamshell conformations of the GluN1 LBD. The glycan on GluN2B-N688 shows a similar, though weaker, effect. Based on these results, and assuming the transferability of the results of LBD simulations to the full receptor, we predict that glycans at GluN1-N440 might play a potentiator role in NMDARs. To validate this prediction, we perform electrophysiological analysis of full-length NMDARs with a glycosylation-preventing GluN1-N440Q mutation, and demonstrate an increase in the glycine EC50 value. Overall, our results suggest an intramolecular potentiating role of glycans on NMDA receptors.

  9. Effect of urea-molasses block supplementation on grazing weaner goats naturally infected with gastrointestinal nematodes

    Directory of Open Access Journals (Sweden)

    R.M. Waruiru

    2004-11-01

    Full Text Available The influence of feeding urea-molasses blocks (UMB on growth and gastrointestinal (GI nematode parasitism of weaner goats grazing the same pasture was investigated on a farm in Nyandarua District, Kenya. Thirty female Small East African goat kids at an average age of 5 months were initially treated with albendazole orally (5 mg kg-1 body mass and randomly assigned into one of two groups: group I were fed UMB prepared using a cold process and group II kids (controls received no block supplementation (NBS. The UMB were given in the evening when the animals returned from grazing and were consumed during the night at a rate of 95.0 g head-1 day-1. Supplementation was undertaken for 3 consecutive months from July to September 2001 and January to March 2002. Body mass of the kids and faecal egg counts were measured monthly and larval cultures were performed on positive faecal samples of kids of each group. Five goats from each group were randomly selected for slaughter and total counts and identification of worms at the end of June 2002. Significant differences (P < 0.05 were found in cumulative mass gains of kids in group I from September compared with those in group II. On termination of the study kids in group I had gained an average of (+ SD 20.4 ± 1.4 kg while those in group II had gained 11.8 + 1.1 kg. From January 2002, faecal egg counts of the kids in the UMB group differed significantly (P < 0.05 from those of the NBS group and at slaughter, the mean (+ SD worm counts for the UMB group was 482 + 299 while that of the NBS group was 1 302 + 410. In all the goats, Haemonchus contortus was the predominant nematode recovered. These results indicate that UMB had significant effects in the control of GI nematode parasitism and enhanced growth of the young goats.

  10. The Effect of Blocking Screws on Union of Infraisthmal Femur Fractures Stabilized with a Retrograde Intramedullary Nail.

    Science.gov (United States)

    Van Dyke, Bryan; Colley, Ryan; Ottomeyer, Christina; Palmer, Ryan; Pugh, Kevin

    2018-01-05

    To investigate the effect of blocking screws on the union rate and stability of infra-isthmal femur fractures treated with retrograde intramedullary nail (RIMN) insertion. Retrospective cohort study SETTING:: A single level 1 trauma centerPatients/Participants: All patients with an infra-isthmal femur fracture treated with a RIMN from 2005 to 2012. All fractures were treated with a RIMN. Blocking screws (BS) were used at the discretion of the treating surgeon. 1) Radiographic time to union, 2) Initial post-operative sagittal and coronal angulation, and 3) Final sagittal and coronal angulation RESULTS:: Neither the average time to union (BS 21.1 weeks vs. 21.8 weeks), nor union rates (BS 61% vs. 77%) were statistically different between blocking screw and non-blocking screw constructs. No significant alignment differences existed whether BS were used or not. In this study, we were not able to verify our hypothesis. In fact, we did not find any significant advantages when blocking screws were added to a retrograde intramedullary nail construct for distal femur fractures with respect to union time, union rate, or improvements in alignment. Additional studies are needed to determine the actual benefit of blocking screws in the treatment of infra-isthmal femoral shaft fractures treated with retrograde intramedullary nailing.

  11. Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis.

    Science.gov (United States)

    Stanley, William; Drum, Melissa; Nusstein, John; Reader, Al; Beck, Mike

    2012-05-01

    The inferior alveolar nerve (IAN) block does not always result in successful pulpal anesthesia. Anesthetic success rates might be affected by increased anxiety. Nitrous oxide has been shown to have both anxiolytic and analgesic properties. Therefore, the purpose of this prospective, randomized, double-blind, placebo-controlled study was to determine the effect of nitrous oxide on the anesthetic success of the IAN block in patients experiencing symptomatic irreversible pulpitis. One hundred emergency patients diagnosed with symptomatic irreversible pulpitis of a mandibular posterior tooth were enrolled in this study. Each patient was randomly assigned to receive an inhalation regimen of nitrous oxide/oxygen mix or room air/oxygen mix (placebo) 5 minutes before the administration of the IAN block. Endodontic access was begun 15 minutes after completion of the IAN block, and all patients had profound lip numbness. Success was defined as no or mild pain (visual analog scale recordings) on access or instrumentation. The success rate for the IAN block was 50% for the nitrous oxide group and 28% for the placebo group. There was a statistically significant difference between the 2 groups (P = .024). For mandibular teeth diagnosed with symptomatic irreversible pulpitis, administration of 30%-50% nitrous oxide resulted in a statistically significant increase in the success of the IAN block compared with room air/oxygen. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  12. Involvement of hippocampal NMDA receptors in encoding and consolidation, but not retrieval, processes of spontaneous object location memory in rats.

    Science.gov (United States)

    Yamada, Kazuo; Arai, Misaki; Suenaga, Toshiko; Ichitani, Yukio

    2017-07-28

    The hippocampus is thought to be involved in object location recognition memory, yet the contribution of hippocampal NMDA receptors to the memory processes, such as encoding, retention and retrieval, is unknown. First, we confirmed that hippocampal infusion of a competitive NMDA receptor antagonist, AP5 (2-amino-5-phosphonopentanoic acid, 20-40nmol), impaired performance of spontaneous object location recognition test but not that of novel object recognition test in Wistar rats. Next, the effects of hippocampal AP5 treatment on each process of object location recognition memory were examined with three different injection times using a 120min delay-interposed test: 15min before the sample phase (Time I), immediately after the sample phase (Time II), and 15min before the test phase (Time III). The blockade of hippocampal NMDA receptors before and immediately after the sample phase, but not before the test phase, markedly impaired performance of object location recognition test, suggesting that hippocampal NMDA receptors play an important role in encoding and consolidation/retention, but not retrieval, of spontaneous object location memory. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Repeated Blockade of NMDA Receptors during Adolescence Impairs Reversal Learning and Disrupts GABAergic Interneurons in Rat Medial Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Jitao eLi

    2016-03-01

    Full Text Available Adolescence is of particular significance to schizophrenia, since psychosis onset typically occurs in this critical period. Based on the N-methyl-D-aspartate (NMDA receptor hypofunction hypothesis of schizophrenia, in this study, we investigated whether and how repeated NMDA receptor blockade during adolescence would affect GABAergic interneurons in rat medial prefrontal cortex (mPFC and mPFC-mediated cognitive functions. Specifically, adolescent rats were subjected to intraperitoneal administration of MK-801 (0.1, 0.2, 0.4 mg/kg, a non-competitive NMDA receptor antagonist, for 14 days and then tested for reference memory and reversal learning in the water maze. The density of parvabumin (PV-, calbindin (CB- and calretinin (CR-positive neurons in mPFC were analyzed at either 24 hours or 7 days after drug cessation. We found that MK-801 treatment delayed reversal learning in the water maze without affecting initial acquisition. Strikingly, MK-801 treatment also significantly reduced the density of PV+ and CB+ neurons, and this effect persisted for 7 days after drug cessation at the dose of 0.2 mg/kg. We further demonstrated that the reduction in PV+ and CB+ neuron densities was ascribed to a downregulation of the expression levels of PV and CB, but not to neuronal death. These results parallel the behavioral and neuropathological changes of schizophrenia and provide evidence that adolescent NMDA receptors antagonism offers a useful tool for unraveling the etiology of the disease.

  14. The effect of film thickness and molecular structure on order and disorder in thin films of compositionally asymmetric block copolymers

    Science.gov (United States)

    Mishra, Vindhya

    Directed self-assembly of thin film block copolymers offer a high throughput-low cost route to produce next generation lithographic devices, if one can bring the defect densities in the self assembled patterns below tolerance limits. However, the ability to control the nanoscale structure or morphology in thin film block copolymers presents challenges due to confinement effects on equilibrium behavior. Using structure characterization techniques such as grazing incidence small angle X-ray scattering (GISAXS), transmission electron and atomic force microscopy as well as self-consistent field theory, we have investigated how film thickness, annealing temperature and block copolymer structure affects the equilibrium behavior of asymmetric block copolymer films. Our studies have revealed the complicated dependence of order-disorder transitions, order-order transitions and symmetry transitions on film thickness. We found that the thickness dependent transition in the packing symmetry of spherical morphology diblock copolymers can be suppressed by blending with a small amount of majority block homopolymer, which allowed us to resolve the driving force behind this transition. Defect densities in, and the order-disorder transition temperature of, thin films of graphoepitaxially aligned diblock copolymer cylinders showed surprising sensitivity to the microdomain spacing. Methods to mitigate defect formation in thin films have been identified. The challenge of quantification of structural order in these systems was overcome using GISAXS, which allowed us to study the phenomena of disordering in two and three dimensions. Through studies on block copolymers which exhibit an order-order transition in bulk, we found that that subtle differences in the packing frustration of the spherical and cylindrical phases as well as the higher configurational entropy of free chain ends at the surface can drive the equilibrium configuration in thin films away from the stable bulk structure

  15. The transversus abdominis plane block provides effective postoperative analgesia in patients undergoing total abdominal hysterectomy.

    LENUS (Irish Health Repository)

    Carney, John

    2008-12-01

    Patients undergoing total abdominal hysterectomy suffer significant postoperative pain. The transversus abdominis plane (TAP) block is a recently described approach to providing analgesia to the anterior abdominal wall. We evaluated the analgesic efficacy of the TAP block in patients undergoing total abdominal hysterectomy via a transverse lower abdominal wall incision, in a randomized, controlled, double-blind clinical trial.

  16. Effect of dexamethasone in low volume supraclavicular brachial plexus block: A double-blinded randomized clinical study

    Directory of Open Access Journals (Sweden)

    Arun Kumar Alarasan

    2016-01-01

    Full Text Available Background and Aims: With the use of ultrasound, a minimal effective volume of 20 ml has been described for supraclavicular brachial plexus block. However achieving a long duration of analgesia with this minimal volume remains a challenge. We aimed to determine the effect of dexamethasone on onset and duration of analgesia in low volume supraclavicular brachial plexus block. Material and Methods: Sixty patients were randomly divided into two groups of 30 each. Group C received saline (2 ml + 20 ml of 0.5% bupivacaine and Group D received dexamethasone (8 mg + 20 ml of 0.5% bupivacaine in supraclavicular brachial plexus block. Hemodynamic variables and visual analog scale (VAS score were noted at regular intervals until 450 min. The onset and duration of sensory and motor block were measured. The incidence of "Halo" around brachial plexus was observed. Student′s t-test and Chi-square test were used for statistical analysis. Results: The onset of sensory and motor block was significantly earlier in dexamethasone group (10.36 ± 1.99 and 12 ± 1.64 minutes compared to control group (12.9 ± 2.23 and 18.03 ± 2.41 minutes. The duration of sensory and motor block was significantly prolonged in dexamethasone group (366 ± 28.11 and 337.33 ± 28.75 minutes compared to control group (242.66 ± 26.38 and 213 ± 26.80 minutes. The VAS score was significantly lower in dexamethasone group after 210 min. "Halo" was present around the brachial plexus in all patients in both the groups. Conclusion: Dexamethasone addition significantly increases the duration of analgesia in patients receiving low volume supraclavicular brachial plexus block. No significant side-effects were seen in patients receiving dexamethasone as an adjunct.

  17. Urea decreases specific ion effects on the LCST of PMMA-block-PDMAEMA aggregates

    Directory of Open Access Journals (Sweden)

    João Carlos Perbone de Souza

    2014-12-01

    Full Text Available Urea is a well-known additive used as a mild protein denaturant. The effect of urea on proteins, micellar systems and other colloids is still under debate. In particular, urea has shown interesting effects on the ion binding in systems like charged micelles, vesicles or Langmuir-Blodgett films. The urea effect on polymeric aggregates in water is still an open field. For instance, the additive may affect properties such as cmc, LCST, UCST and others. In particular, LCST is a property that can be very convenient for designing smart systems that respond to temperature. Previous studies have indicated that the LCST of positive charged copolymers aggregates based on poly[N-dimethyl(ethylamine methacrylate], PDMAEMA, can be nicely modulated by anions in aqueous solution and such phenomenon depends on the nature of the anion present. In this work, it has been demonstrated that urea also affects the LCST of PMMA-block-PDMAEMA aggregates in aqueous solution. In addition, in the presence of high concentrations of the additive, the specific behavior of the anions is lost, supporting the general mechanism of urea reducing the differences on ion binding to surfaces in aqueous solutions. To the best of our knowledge, this is the first time those phenomena are shown in polymer micelles.

  18. A Rare Side Effect due to TNF-Alpha Blocking Agent: Acute Pleuropericarditis with Adalimumab

    Directory of Open Access Journals (Sweden)

    Hakan Ozkan

    2013-01-01

    Full Text Available Tumor necrosis factor-alpha antagonism is an important treatment strategy in patients with rheumatoid arthritis, psoriatic arthritis, vasculitis, and ankylosing spondylitis. Adalimumab is one of the well-known tumor necrosis factor-alpha blocking agents. There are several side effects reported in patients with adalimumab therapy. Cardiac side effects of adalimumab are rare. Only a few cardiac side effects were reported. A 61-year-old man treated with adalimumab for the last 6 months due to psoriatic arthritis presented with typically acute pleuropericarditis. Chest X-ray and echocardiography demonstrated marked pericardial effusion. Patient was successfully evaluated for the etiology of acute pleuro-pericarditis. Every etiology was excluded except the usage of adalimumab. Adalimumab was discontinued, and patient was treated with 1200 mg of ibuprofen daily. Control chest X-ray and echocardiography after three weeks demonstrated complete resolution of both pleural and pericardial effusions. This case clearly demonstrated the acute onset of pericarditis with adalimumab usage. Acute pericarditis and pericardial effusion should be kept in mind in patients with adalimumab treatment.

  19. Leukotriene enhances NMDA-induced inward currents in dorsal horn neurons of the rat spinal cord after peripheral nerve injury.

    Science.gov (United States)

    Kiyoyuki, Yasukuni; Taniguchi, Wataru; Okubo, Masamichi; Yamanaka, Hiroki; Kobayashi, Kimiko; Nishio, Naoko; Nakatsuka, Terumasa; Noguchi, Koichi

    2015-09-09

    LTB4 is classified as a leukotriene (LT), a group of lipid mediators that are derived from arachidonic acid. It is recognized that leukotrienes are involved in the pathogenesis of many diseases, including peripheral inflammatory pain. However, little is known about the effects of leukotrienes on the spinal dorsal horn during neuropathic pain. Previously, we reported that there was increased expression of 5-lipoxygenase (5-LO) at spinal microglia, and the leukotriene B4 receptor 1 (BLT1), a high affinity receptor of LTB4, in spinal neurons in spared nerve injury (SNI) model rats. In the present study, we examined the effects of LTB4 on spinal dorsal horn neurons in both naïve and SNI model rats using patch-clamp methods. Bath application of LTB4 did not change AMPA receptor-mediated spontaneous excitatory postsynaptic currents (sEPSCs) or membrane potentials. However, we found that LTB4 enhanced the amplitude of NMDA receptor-mediated sEPSCs and significantly increased exogenous NMDA-induced inward currents in SNI model rats. This increase of inward currents could be inhibited by a selective LTB4 antagonist, U75302, as well as a GDP-β-S, a G-protein inhibitor. These results indicate that both increased LTB4 from spinal microglia or increased BLT1 in spinal neurons after peripheral nerve injury can enhance the activity of NMDA receptors through intracellular G-proteins in spinal dorsal horn neurons. Our findings showed that LTB4, which may originate from microglia, can activate BLT1 receptors which are expressed on the membrane of spinal dorsal horn neurons during neuropathic pain. This glia-neuron interaction induces the enhancement of NMDA currents through intracellular G-proteins. The enhancement of NMDA receptor sensitivity of dorsal horn neurons may lead to central sensitization, leading to mechanical pain hypersensitivity.

  20. Stress-restress evokes sustained iNOS activity and altered GABA levels and NMDA receptors in rat hippocampus

    DEFF Research Database (Denmark)

    Harvey, Brian H; Oosthuizen, Frasia; Brand, Linda

    2004-01-01

    . The NOS isoform involved, and the role of stress-mediated corticosterone release in NOS activation, was verified with the administration of selective iNOS and nNOS inhibitors, aminoguanidine (50 mg/kg/day i.p.) and 7-nitroindazole (12.5 mg/kg/day i.p.), and the steroid synthesis inhibitor, ketoconazole...... (24 mg/kg/day i.p.), administered for 21 days prior to and during the stress procedure. RESULTS: Stress evoked a sustained increase in NOS activity, but reduced NMDA receptor density and total GABA levels. Aminoguanidine or ketoconazole, but not 7-nitroindazole or saline, blocked stress-induced NOS...

  1. The Effect of Coloring and Compacting Pressure Paving Block by Adding 5 Wt.% Fly Ash in The Compressive Strength

    Science.gov (United States)

    Nurzal; Nursyuhada, Aries

    2017-12-01

    This research aims based on SNI 03-0691-1996 to investigate the effect of coloring and compacting pressure with the addition of 5 wt.% fly ash (Fa) on compressive strength. Fa derived from waste material coal-fired Sijantang Sawahlunto thermal power plant. The growing production of Fa caused negative environmental impact. So, one of the solutions to overcome that effects is to use the Fa as a raw material for paving block mixture that can reduce the cost of raw material and increase its strength. Paving blocks are gray and red with 0 wt.%, 5 wt.% Fa + Pb composition. Compaction pressure variations 55, 65, 75, 85 and 95 Kg/cm2. The drying time for 35 days. Specimens were produced in the form of rectangular bar (length, L = 20 cm, width, B = 10 cm, thickness, W = 6 cm). The test results showed that the addition of 5 wt% FA has a compressive strength value higher than 0 wt%. The red color has a compressive strength lower than the gray color paving block caused the red color (Iron Oxide) is less binding at the time of mixing the material. Gray and red Paving blocks both increase in each additional compaction pressure, because the higher the compaction pressure will increase the bond between the particles so porosity is reduced increased compressive strength. The overall data, the gray paving block with the composition of 5 wt% FA at compaction pressure 95 kg/cm2 with the optimal compressive strength value of 36.1 MPa and the lowest value is found in the red color paving block at 0 wt% FA at a pressure of 55 kg/cm2 with a value of 6.5 MPa. Gray and red Color paving blocks has a compressive strength quality based on SNI 03-0691-1996.

  2. Contrasting effects of acute and chronic treatments with ketamine on ...

    African Journals Online (AJOL)

    NMDA) pathway in the Pathophysiology of anxiety disorder. However the role of NMDA neurotransmission in the neurobiology of different classes of anxiety disorder remains unexplored. This study examined the effects of intraperitoneal ...

  3. Randomized clinical study on the analgesic effect of local infiltration versus spinal block for hemorrhoidectomy

    Directory of Open Access Journals (Sweden)

    Luis Antônio Borges

    2017-05-01

    Full Text Available ABSTRACT BACKGROUND AND OBJECTIVES: Postoperative analgesia and early recovery are important for hospital discharge. The primary objective of this study was to compare the analgesic effectiveness of perianal infiltration and subarachnoid anesthesia for hemorrhoidectomy. The secondary objective was to compare time to discharge, adverse effects and complications. DESIGN AND SETTING: Randomized, prospective and comparative study at Dr. Mário Gatti Hospital. METHODS: Forty patients aged 18-60, in American Society of Anesthesiologists physical status category 1 or 2, were included. The local group (LG received local infiltration (0.75% ropivacaine under general anesthesia; the spinal group (SG received subarachnoid block (2 ml of 0.5% bupivacaine. Analgesic supplementation consisted of fentanyl for LG and lidocaine for SG. Postoperative pain intensity, sphincter relaxation, lower-limb strength, time to discharge, analgesic dose over one week and adverse effects were assessed. RESULTS: Eleven LG patients (52.4% required supplementation, but no SG patients. Pain intensity was higher for LG up to 120 min, but there were no differences at 150 or 180 min. There were no differences in the need for paracetamol or tramadol. Times to first analgesic supplementation and hospital discharge were longer for SG. The adverse effects were nausea, dizziness and urinary retention. CONCLUSIONS: Pain intensity was higher in LG than in SG over the first 2 h, but without differences after 150 and 180 min. Time to first supplementation was shorter in LG. There were no differences in doses of paracetamol and tramadol, or in adverse effects. REGISTRATION: ClinicalTrials.gov NCT02839538.

  4. Lubrication pressure and fractional viscous damping effects on the spring-block model of earthquakes

    Science.gov (United States)

    Tanekou, G. B.; Fogang, C. F.; Kengne, R.; Pelap, F. B.

    2018-04-01

    We examine the dynamical behaviours of the "single mass-spring" model for earthquakes considering lubrication pressure effects on pre-existing faults and viscous fractional damping. The lubrication pressure supports a part of the load, thereby reducing the normal stress and the associated friction across the gap. During the co-seismic phase, all of the strain accumulated during the inter-seismic duration does not recover; a fraction of this strain remains as a result of viscous relaxation. Viscous damping friction makes it possible to study rocks at depth possessing visco-elastic behaviours. At increasing depths, rock deformation gradually transitions from brittle to ductile. The fractional derivative is based on the properties of rocks, including information about previous deformation events ( i.e., the so-called memory effect). Increasing the fractional derivative can extend or delay the transition from stick-slip oscillation to a stable equilibrium state and even suppress it. For the single block model, the interactions of the introduced lubrication pressure and viscous damping are found to give rise to oscillation death, which corresponds to aseismic fault behaviour. Our result shows that the earthquake occurrence increases with increases in both the damping coefficient and the lubrication pressure. We have also revealed that the accumulation of large stresses can be controlled via artificial lubrication.

  5. Effects of ultrasound-guided stellate ganglion block on acute pain after arthroscopic shoulder surgery.

    Science.gov (United States)

    Choi, Eun Mi; Kim, Eun Mi; Chung, Mi Hwa; Park, Jong Hee; Lee, Hyo Keun; Choi, Young Rong; Lee, Mihyeon

    2015-01-01

    Apart from a few case reports, the effectiveness of stellate ganglion block (SGB) as a monotherapy in acute nociceptive pain has not been determined. We aimed to assess the effects of SGB on postoperative pain after arthroscopic shoulder surgery. Randomized, blind, controlled, clinical trial University Hospital outpatient Forty-six patients undergoing arthroscopic shoulder surgery were assigned randomly to 2 groups: group S included patients who underwent SGB prior to surgery and group C did not. In group S, subfascial ultrasound-guided SGB was conducted with 4 mL of 0.375% levobupivacaine. For the first postoperative 48 hours, postoperative visual analog scale (VAS) and analgesic requirements were compared. The results of 40 patients were included in the study. There was no difference between groups with regards to analgesics requirement for the first postoperative 48 hours and no difference in VAS score (P > 0.05). Small number of patients in study. Preoperative ultrasound-guided SGB did not reduce postoperative acute pain in arthroscopic shoulder surgery.

  6. AMPA receptor pHluorin-GluA2 reports NMDA receptor-induced intracellular acidification in hippocampal neurons.

    Science.gov (United States)

    Rathje, Mette; Fang, Huaqiang; Bachman, Julia L; Anggono, Victor; Gether, Ulrik; Huganir, Richard L; Madsen, Kenneth L

    2013-08-27

    NMDA receptor activation promotes endocytosis of AMPA receptors, which is an important mechanism underlying long-term synaptic depression. The pH-sensitive GFP variant pHluorin fused to the N terminus of GluA2 (pH-GluA2) has been used to assay NMDA-mediated AMPA receptor endocytosis and recycling. Here, we demonstrate that in somatic and dendritic regions of hippocampal neurons a large fraction of the fluorescent signal originates from intracellular pH-GluA2, and that the decline in fluorescence in response to NMDA and AMPA primarily describes an intracellular acidification, which quenches the pHluorin signal from intracellular receptor pools. Neurons expressing an endoplasmic reticulum-retained mutant of GluA2 (pH-GluA2 ΔC49) displayed a larger response to NMDA than neurons expressing wild-type pH-GluA2. A similar NMDA-elicited decline in pHluorin signal was observed by expressing cytosolic pHluorin alone without fusion to GluA2 (cyto-pHluorin). Intracellular acidification in response to NMDA was further confirmed by using the ratiometric pH indicator carboxy-SNARF-1. The NMDA-induced decline was followed by rapid recovery of the fluorescent signal from both cyto-pHluorin and pH-GluA2. The recovery was sodium-dependent and sensitive to Na(+)/H(+)-exchanger (NHE) inhibitors. Moreover, recovery was more rapid after shRNA-mediated knockdown of the GluA2 binding PDZ domain-containing protein interacting with C kinase 1 (PICK1). Interestingly, the accelerating effect of PICK1 knockdown on the fluorescence recovery was eliminated in the presence of the NHE1 inhibitor zoniporide. Our results indicate that the pH-GluA2 recycling assay is an unreliable assay for studying AMPA receptor trafficking and also suggest a role for PICK1 in regulating intracellular pH via modulation of NHE activity.

  7. HAEMATOMA BLOCK- AN EFFECTIVE ALTERNATIVE TO GENERAL ANAESTHESIA FOR REDUCTION OF DISTAL RADIUS FRACTURES

    Directory of Open Access Journals (Sweden)

    Prabhati Rani Mishra

    2016-12-01

    Full Text Available BACKGROUND Most common fracture in elderly patients is distal radius fracture. The most common method of management is closed reduction and immobilisation. The aim of the study is to compare the analgesic effects of haematoma block and general anaesthesia for closed reduction of distal fracture of radius. MATERIALS AND METHODS A prospective randomised controlled study was carried out among 100 patients of age group between 15-70 years of either sex who had fracture distal radius between 2015-2016. The patients having multiple fractures, pathological fractures or suffering from any organic diseases were excluded from the study. After taking informed written consent, the patients were randomised into two equal groups. In group A, reduction of fracture was done following administration of IV propofol and in group B after infiltration with 2% lignocaine into fracture haematoma site. Pain score was compared by VAS before, during and after manipulation in both the groups. Time taken from presentation at emergency department to reduction and discharge from hospital was also compared. Statistical analysis was done by applying SPSS software. RESULTS 100 patients of mean age 42.5 years, male: female 43:57 with fracture distal radius were studied. Mean time from admission to fracture reduction in group A was 2.64±0.93 hours and in group B 0.90±0.45 hours (P=0.0001. Discharge time from hospital after reduction of fracture in group A was 4.24±0.94 hours and in group B 0.75±0.2 hours (P=0.0001. VAS during reduction in group A was 0 and in group B 0.98±0.8 (P=0.0001. 10 minutes after reduction VAS in group A was 2.28±0.24 and group B 0.72±0.45 (P=0.0001. CONCLUSION For closed reduction of distal radius fracture, haematoma block with lignocaine is safe and effective alternative to intravenous general anaesthesia with propofol.

  8. Effect of warming bupivacaine 0.5% on ultrasound-guided axillary plexus block. Randomized prospective double-blind study.

    Science.gov (United States)

    Trabelsi, W; Ben Gabsia, A; Lebbi, A; Sammoud, W; Labbène, I; Kchelfi, S; Ferjani, M

    2017-02-01

    To evaluate the effect of warming bupivacaine 0.5% on ultrasound-guided axillary brachial plexus block. Prospective, randomized, double-blind. Eighty patients undergoing elective or emergency surgery beyond the distal third of the upper limb were divided into two groups of 40 patients: the warm group received 15mL bupivacaine 0.5% heated to 37°C; the cold group received 15mL 0.5% bupivacaine stored for at least 24hours in the lower compartment of a refrigerator at 13-15°C. Onset and duration of sensory and motor blocks were evaluated every 5minutes for 40minutes. Postoperative pain was evaluated at 1, 3, 6, 12 and 24hours. Effective analgesia time was recorded as the interval between anesthetic injection and the first analgesia requirement (VAS>30mm). Time to onset of sensory and motor block was significantly shorter in the warm group, and mean duration of sensory and motor block and of postoperative analgesia significantly longer. Warming bupivacaine 0.5% to 37°C accelerated onset of sensory and motor block and extended action duration. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. The effectiveness of regional anaesthesia before and after the introduction of a dedicated regional anaesthesia service incorporating a block room.

    Science.gov (United States)

    Chin, A; Heywood, L; Iu, P; Pelecanos, A M; Barrington, M J

    2017-11-01

    Dedicated regional anaesthesia services incorporating block rooms and/or block teams may facilitate theatre efficiency and improve training in regional anaesthesia. Currently, it is unknown if a dedicated regional anaesthesia service improves the effectiveness of regional anaesthesia. In November 2013, the Royal Brisbane and Women's Hospital established a dedicated regional anaesthesia service comprising a block team and a block room. Pre-intervention (conventional model of care) registry data was retrospectively compared with post-intervention (dedicated regional anaesthesia service) audit data, with regard to pain and opioid requirement in the post-anaesthesia care unit (PACU). The primary outcome was inadequate analgesia, defined as a numerical rating scale (NRS; 0, no pain; 10, worst pain imaginable) for pain >5 in the PACU. Pre- and post-intervention, 43.7% and 27.7% of patients respectively reported a NRS >5 (P improved outcome seen post-intervention. After adjustment for American Society of Anesthesiologists physical status, block type and surgery type, the odds ratio of having inadequate analgesia (NRS >5) was 0.54 (95% confidence interval 0.39 to 0.76) for post-intervention compared to pre-intervention. Secondary outcomes examined pre- and post-intervention were the absence of pain (39.3% and 55.1% of patients, respectively, P P P service was associated with improved effectiveness of regional anaesthesia.

  10. Dysfunctional synapse in Alzheimer's disease - A focus on NMDA receptors.

    Science.gov (United States)

    Mota, Sandra I; Ferreira, Ildete L; Rego, A Cristina

    2014-01-01

    Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly. Alterations capable of causing brain circuitry dysfunctions in AD may take several years to develop. Oligomeric amyloid-beta peptide (Aβ) plays a complex role in the molecular events that lead to progressive loss of function and eventually to neurodegeneration in this devastating disease. Moreover, N-methyl-D-aspartate (NMDA) receptors (NMDARs) activation has been recently implicated in AD-related synaptic dysfunction. Thus, in this review we focus on glutamatergic neurotransmission impairment and the changes in NMDAR regulation in AD, following the description on the role and location of NMDARs at pre- and post-synaptic sites under physiological conditions. In addition, considering that there is currently no effective ways to cure AD or stop its progression, we further discuss the relevance of NMDARs antagonists to prevent AD symptomatology. This review posits additional information on the role played by Aβ in AD and the importance of targeting the tripartite glutamatergic synapse in early asymptomatic and possible reversible stages of the disease through preventive and/or disease-modifying therapeutic strategies. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Distribution of interleukin-1 receptor complex at the synaptic membrane driven by interleukin-1β and NMDA stimulation.

    Science.gov (United States)

    Gardoni, Fabrizio; Boraso, Mariaserena; Zianni, Elisa; Corsini, Emanuela; Galli, Corrado L; Cattabeni, Flaminio; Marinovich, Marina; Di Luca, Monica; Viviani, Barbara

    2011-02-11

    Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that contributes to neuronal injury in various degenerative diseases, and is therefore a potential therapeutic target. It exerts its biological effect by activating the interleukin-1 receptor type I (IL-1RI) and recruiting a signalling core complex consisting of the myeloid differentiation primary response protein 88 (MyD88) and the IL-1R accessory protein (IL-1RAcP). This pathway has been clearly described in the peripheral immune system, but only scattered information is available concerning the molecular composition and distribution of its members in neuronal cells. The findings of this study show that IL-1RI and its accessory proteins MyD88 and IL-1RAcP are differently distributed in the hippocampus and in the subcellular compartments of primary hippocampal neurons. In particular, only IL-1RI is enriched at synaptic sites, where it co-localises with, and binds to the GluN2B subunit of NMDA receptors. Furthermore, treatment with NMDA increases IL-1RI interaction with NMDA receptors, as well as the surface expression and localization of IL-1RI at synaptic membranes. IL-1β also increases IL-1RI levels at synaptic sites, without affecting the total amount of the receptor in the plasma membrane. Our results reveal for the first time the existence of a dynamic and functional interaction between NMDA receptor and IL-1RI systems that could provide a molecular basis for IL-1β as a neuromodulator in physiological and pathological events relying on NMDA receptor activation.

  12. Mechanism of the hypotensive effect of a new beta-adrenergic blocking drug, arotinolol (S-596) in anesthetized rabbits.

    Science.gov (United States)

    Nakahara, H; Nakazawa, M; Tsukada, T; Imai, S

    1985-10-01

    The mechanism of the hypotensive effect of arotinolol (dl-2-(3'-t-butylamino-2'-hydroxypropylthio)-4-(5'-carbamoyl-2'-th ienyl) thiazole hydrochloride, S-596), a new beta-adrenergic blocking drug with a weak alpha-adrenergic blocking activity, was studied in anesthetized rabbits. Intravenously administered arotinolol produced hypotension at doses above 3 micrograms/kg. Postganglionic renal nerve impulses (RNI) were effect-dependently at doses of 3 and 30 micrograms/kg but augmented after 300 micrograms/kg of arotinolol. The effects of the lower doses of arotinolol were similar to those of clonidine or propranolol, while the effects of the higher doses were similar to those of nitroprusside or phentolamine. The regression line representing the relation between the per cent change of the resting blood pressure and that of the numbers of RNI produced by the lower doses of arotinolol coincided with that of propranolol. Arotinolol blocked the pressor response to phenylephrine but not that to noradrenaline. Administration of arotinolol via the carotid artery produced a hypotension and a concomitant decrease of the numbers of RNI at doses of 3 to 30 micrograms/kg. The above results suggest that the hypotension produced by lower doses of arotinolol was attributable to a decreased sympathetic nervous activity, as is the case with propranolol, while the hypotension by higher doses was peripheral in origin, occurring as a consequence of the blocking effect on the alpha 1-adrenoceptor.

  13. Effect of dexamethasone added to lidocaine in supraclavicular brachial plexus block: A prospective, randomised, double-blind study

    Directory of Open Access Journals (Sweden)

    Prashant A Biradar

    2013-01-01

    Full Text Available Background: Different additives have been used to prolong brachial plexus block. We performed a prospective, randomised, double-blind study to evaluate the effect of dexamethasone added to lidocaine on the onset and duration of supraclavicular brachial plexus block as this is the most common type of brachial block performed in our institute. Methods: Sixty American Society of Anaesthesiologist′s physical status I and II patients undergoing elective hand, forearm and elbow surgery under brachial plexus block were randomly allocated to receive either 1.5% lidocaine (7 mg/kg with adrenaline (1:200,000 and 2 ml of normal saline (group C, n=30 or 1.5% lidocaine (7 mg/kg with adrenaline (1:200,000 and 2 ml of dexamethasone (8 mg (group D, n=30. The block was performed using a nerve stimulator. Onset and duration of sensory and motor blockade were assessed. The sensory and motor blockade of radial, median, ulnar and musculocutaneous nerves were evaluated and recorded at 5, 10, 20, 120 min, and at every 30 min thereafter. Results: Two patients were excluded from the study because of block failure. The onset of sensory and motor blockade (13.4±2.8 vs. 16.0±2.3 min and 16.0±2.7 vs. 18.7±2.8 min, respectively were significantly more rapid in the dexamethasone group than in the control group ( P=0.001. The duration of sensory and motor blockade (326±58.6 vs. 159±20.1 and 290.6±52.7 vs. 135.5±20.3 min, respectively were significantly longer in the dexamethasone group than in the control group ( P=0.001. Conclusion: Addition of dexamethasone to 1.5% lidocaine with adrenaline in supraclavicular brachial plexus block speeds the onset and prolongs the duration of sensory and motor blockade.

  14. STUDY & EVALUATE THE COMPARISON OF PLAIN LIGNOCAINE AND LIGNACAINE WITH SODIUM BICARBONATE EFFECTS IN SUPRACLAVICULAR BRACHIAL PLEXUS BLOCK

    Directory of Open Access Journals (Sweden)

    Vijetha

    2015-08-01

    Full Text Available BACKGROUND & AIMS : supraclavicular brachial plexus block is usually used to anaesthetize the upper limb for the purpose of upper limb surgeries. Drugs like Lignocaine , Bupiv a caine are used for this block and some additives are added to prolong the duration and quality of bl ockade. The present study is aimed to evaluate the comparison of plain lignocaine and lign o caine with sodium bicarbonate in supraclavicular brachial plexus block by means of the onset time of sensory and motor blockade, the quality of sensory and motor blo ckade , and the duration of blockade . METHODS : Sixty patients aged between 18 and 60 years of physical status ASA 1 and 2 undergoing upper limb surgeries lasting more than 30 minutes were included in the study. The patients were randomly allocated into two groups. Supraclavicular brachial plexus block was performed after eliciting paraesthesia. The patients in Group I (n=30 received 25ml of 1% plain lignocaine (prepared by adding 12.5ml of distilled water to 12.5ml of 2% plain lignocaine. The patients in th e Group II (study group received 25ml of 1% alkalinized lignocaine (prepared by adding 3ml of 7.5% sodium bicarbonate and 9.5ml of distilled water to 12.5ml of 2% plain lignocaine. RESULTS : The present study entitled Comparison of effects of plain lignoc aine and lignocaine with sodium bicarbonate on brachial plexus block concludes that, the onset time of sensory and motor blockade is lesser with sodium bicarbonate added lignocaine (4.13, 11.1minutes when compared to plain lignocaine(9.73, 21.1minutes in supraclavicular brachial plexus block, the quality of sensory and motor blockade is better with sodium bicarbonate added lignocaine, the duration of motor and sensory blockade was significantly prolonged when lignocaine with sodium bicarbonate was used in supraclavicular brachial plexus block

  15. Effect of conduction block in classification and prognosis of Guillain-Barre syndrome

    Directory of Open Access Journals (Sweden)

    Yu-Chen Wang

    2014-09-01

    Full Text Available Aim: The aim was to investigate the electro-physiological characteristics in disease progression of Guillain-Barre syndrome (GBS and observe the effect of conduction block (CB in classification and severity of the disease. Methods: Two hundred and ninety-four patients with GBS were divided into acute inflammatory demyelinating poly-neuropathy (AIDP group, acute motor axonal neuropathy (AMAN group and equivocal group according to their electro-physiological results and then reclassificated after electro-physiological review. All of the patients were followed for 6 months since their attacks. Results: Bad prognosis is more pronounced in AMAN group than in AIDP group (P < 0.05. Most of the patients classificated as AIDP transformed into AMAN when CB occurred in the early phase of the disease. There is a positive relationship between CB in the early phase of the disease and severity of illness (P < 0.05, but CB showed no correlation with prognosis of the patients (P > 0.05. Conclusion: CB in the early phase of GBS indicates the probability of AIDP transforming into AMAN; it suggests that patients with CB in the early phase of the disease might be in serious conditions in a certain extent.

  16. The effects of block training on pacing during 20-km cycling time trial.

    Science.gov (United States)

    Costa, Vitor Pereira; Guglielmo, Luiz Guilherme Antonacci; Paton, Carl David

    2017-04-01

    The aim of this study was to determine the effects of block training (BL) on pacing during a 20-km hilly cycling time trial (TT) in trained cyclists. Twenty male cyclists were separated into 2 groups: control and BL. The training of each cyclist was monitored during a period of 3 weeks. In the first week cyclists performed an overload period of 7 consecutive days of high-intensity interval training followed by 2 weeks of normal training. Cyclists performed 1 TT before intervention and 2 TT after 7 and 14 days at the end of training. Each training session consisted of 10 sets of 3 repeated maximal-effort sprints (15, 30, and 45 s) with an effort/recovery duration ratio of 1:5. The main finding of this study was that the power output displayed a significantly higher start from the start until the halfway point of the TT (p power output was characterized by a significant higher end spurt in the final 2 km in the BL after 2 weeks at the end of training (p power output in the beginning and final part of the TT in trained cyclists.

  17. Beaded nanofibers assembled from double-hydrophobic elastin-like block polypeptides: Effects of trifluoroethanol.

    Science.gov (United States)

    Le, Duc H T; Okubo, Tatsuya; Sugawara-Narutaki, Ayae

    2015-03-01

    A "double-hydrophobic" elastin-like triblock polypeptide GPG has been constructed by mimicking the localization of proline- and glycine-rich hydrophobic domains of native elastin, a protein that provides elasticity and resilience to connective tissues. In this study, the effects of trifluoroethanol (TFE), an organic solvent that strongly affects secondary structures of polypeptides on self-assembly of GPG in aqueous solutions were systematically studied. Beaded nanofiber formation of GPG, where nanoparticles are initially formed by coacervation of the polypeptides followed by their connection into one-dimensional nanostructures, is accelerated by the addition of TFE at the concentrations up to 30% (v/v), whereas aggregates of nanoparticles are formed at 60% TFE. The concentration-dependent assembly pattern discussed is based on the influence of TFE on the secondary structures of GPG. Well-defined nanofibers whose diameter and secondary structures are controlled by TFE concentration may be ideal building blocks for constructing bioelastic materials in tissue engineering. © 2014 Wiley Periodicals, Inc.

  18. Effect of Variable Amplitude Blocks' Ordering on the Functional Fatigue of Superelastic NiTi Wires

    Science.gov (United States)

    Soul, Hugo; Yawny, Alejandro

    2017-12-01

    Accumulation of superelastic cycles in NiTi uniaxial element generates changes on the stress-strain response. Basically, there is an uneven drop of martensitic transformation stress plateaus and an increase of residual strain. This evolution associated with deterioration of superelastic characteristics is referred to as "functional fatigue" and occurs due to irreversible microstructural changes taking place each time a material domain transforms. Unlike complete cycles, for which straining is continued up to elastic loading of martensite, partial cycles result in a differentiated evolution of those material portions affected by the transformation. It is then expected that the global stress-strain response would reflect the previous cycling history of the specimen. In the present work, the consequences of cycling of NiTi wires using blocks of different strain amplitudes interspersed in different sequences are analyzed. The effect of successive increasing, successive decreasing, and interleaved strain amplitudes on the evolution of the superelastic response is characterized. The feasibility of postulating a functional fatigue criterion similar to the Miner's cumulative damage law used in structural fatigue analysis is discussed. The relation of the observed stress-strain response with the transformational history of the specimen can be rationalized by considering that the stress-induced transformation proceeds via localized propagating fronts.

  19. Steroids block the anti-inflammatory effects of low level laser therapy

    Science.gov (United States)

    Lopes-Martins, Rodrigo Alvaro B.; Albertini, Regiane; Lopes-Martins, Patricia Sardinha L.; Iversen, Vegard V.; Bjordal, Jan M.

    2006-02-01

    Objective: Concomitant use of multiple therapies is common in musculoskeletal and airway disorders. Low level laser therapy (LLLT) is considered a promising therapy in arthritis, tendinopathies and rhinitis. We designed two animal studies to assess if the expected anti-inflammatory effect LLLT could be affected by resection of the adrenal gland or concomitant use of the cortisol antagonist mifepristone. Methods: Two studies were performed, with 40 male Wistar rats and with 40 Balb C male mice respectively.. In both studies, four groups received carrageenan and one control group received saline. At 1, 2, and 3 hours after injections, LLLT irradiation was performed with a dose of 7.5 J/cm2. In the rat study, two of the carrageenan groups had the adrenal gland dissected. In the mice study, two of the carrageenan-injected groups were in addition pre-treated with orally administered mifepristone. Results: In the rat paw study, LLLT reduced edema significantly compared to the carrageenan only group (1.5 vs 0.9 ml, padrenal gland resected. In carrageenan-induced pleurisy, LLLT significantly reduced the number of leukocyte cells ( p<0.0001, Mean 34.5 [95%CI: 32.8 - 36.2] versus 87.7 [95%CI: 81.0 - 94.4]), and that the effect of LLLT could be totally blocked by adding the cortisol antagonist mifepristone ( p<0.0001, Mean 34.5 [95%CI: 32.1 - 36.9] versus 82.9 [95%CI: 70.5 - 95.3]). Conclusion: Steroid therapy should not be used concomitantly with LLLT, as the anti-inflammatory effect of LLLT is lost if cortisol receptors are downregulated.

  20. Intracellular calcium elevation during plateau potentials mediated by extrasynaptic NMDA receptor activation in rat hippocampal CA1 pyramidal neurons is primarily due to calcium entry through voltage-gated calcium channels.

    Science.gov (United States)

    Oda, Yoshiaki; Kodama, Satoshi; Tsuchiya, Sadahiro; Inoue, Masashi; Miyakawa, Hiroyoshi

    2014-05-01

    We reported previously that plateau potentials mediated by extrasynaptic N-methyl-d-aspartate receptors (NMDARs) can be induced either by synaptic stimulation in the presence of glutamate transporter antagonist or by iontophoresis of NMDA in rat hippocampal CA1 pyramidal neurons. To examine whether the plateau potentials are accompanied by an elevation of intracellular Ca2+ and to determine the source of Ca2+ elevation, we performed Ca2+ imaging during the plateau potential. Neurons were loaded with Ca2+ indicator fluo-4, and the plateau potentials were generated either synaptically in the presence of glutamate transporter antagonist or by iontophoretically applying NMDA. We have found that a transient elevation in intracellular Ca2+ accompanies the plateau potential. The synaptically induced plateau potential and the Ca2+ elevation were blocked by 5,7-dichlorokynurenic acid (5,7-dCK), an antagonist for the glycine-binding sites of NMDAR. A mixture of Cd2+ and tetrodotoxin did not block NMDA-induced plateau potentials, but completely abolished the accompanying Ca2+ elevation in both the presence and absence of Mg2+ ions in the bathing solution. The NMDA-induced plateau potential was blocked by further adding 5,7-dCK. Our results show that the NMDAR-mediated plateau potential is accompanied by elevation of intracellular Ca2+ that is primarily caused by the influx of Ca2+ through voltage-gated Ca2+ channels. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  1. Pretreatment with 5-hydroxymethyl-2-furaldehyde blocks scopolamine-induced learning deficit in contextual and spatial memory in male mice.

    Science.gov (United States)

    Lee, Younghwan; Gao, Qingtao; Kim, Eunji; Lee, Younghwa; Park, Se Jin; Lee, Hyung Eun; Jang, Dae Sik; Ryu, Jong Hoon

    2015-07-01

    5-Hydroxymethyl-2-furaldehyde (5-HMF) is a compound derived from the dehydration of certain sugars. The aim of the present study was to evaluate the effect of 5-HMF on the cognitive impairment induced by scopolamine, a muscarinic receptor antagonist. To measure various cognitive functions, we conducted the step-through passive avoidance task, the Y-maze task and the Morris water maze task. A single administration of 5-HMF (5 or 10mg/kg, p.o.) significantly attenuates scopolamine-induced cognitive impairment in these behavioral tasks without changes in locomotor activity, and the effect of 5-HMF on scopolamine-induced cognitive impairment was significantly reversed by a sub-effective dose of MK-801, an NMDA receptor antagonist. In addition, a single administration of 5-HMF (10mg/kg, p.o.) enhanced the cognitive performance of normal naïve mice in the passive avoidance task. Furthermore, Western blot analysis revealed that the levels of phosphorylated Ca(2+)/calmodulin-dependent protein kinase II-α (CaMKII) and extracellular signal-regulated kinases (ERK) were significantly enhanced by the single administration of 5-HMF in the hippocampal tissues. Taken together, the present study suggests that 5-HMF may block scopolamine-induced learning deficit and enhance cognitive function via the activation of NMDA receptor signaling, including CaMKII and ERK, and would be an effective candidate against cognitive disorders, such as Alzheimer's disease. Copyright © 2015. Published by Elsevier Inc.

  2. Effect of preoperative alprazolam on the success of inferior alveolar nerve block for teeth with irreversible pulpitis.

    Science.gov (United States)

    Khademi, Abbas Ali; Saatchi, Masoud; Minaiyan, Mohsen; Rostamizadeh, Nasim; Sharafi, Fatemeh

    2012-10-01

    Success of inferior alveolar nerve (IAN) block decreases in patients with irreversible pulpitis. The purpose of this study was to evaluate the effect of preoperative administration of alprazolam on the success of the IAN block for teeth with irreversible pulpitis. Sixty patients with irreversible pulpitis of a mandibular molar were selected for this prospective, randomized, double-blind, placebo-controlled study. The patients received identical capsules of either 0.5 mg of alprazolam or placebo 45 minutes before the administration of a conventional IAN block. Access cavity preparation was initiated 15 minutes after the IAN block injection. Lip numbness was recorded for all the patients. Success was defined as no or mild pain on the basis of visual analogue scale recordings during access cavity preparation and initial instrumentation. Data were analyzed by t test, Mann-Whitney, and χ(2) tests. The success rate was 53% for alprazolam group and 40% for placebo group, with no significant difference between the 2 groups (P = .301). Within the scope of the current study, preoperative oral administration of 0.5 mg of alprazolam did not improve the success of the IAN block in mandibular molars in patients with irreversible pulpitis, and the success rate was not adequate to ensure profound pulpal anesthesia. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  3. Effects of withdrawal rate and starter block size on crystal orientation of a single crystal Ni-based superalloy

    Science.gov (United States)

    Rezaei, M.; Kermanpur, A.; Sadeghi, F.

    2018-03-01

    Fabrication of single crystal (SC) Ni-based gas turbine blades with a minimum crystal misorientation has always been a challenge in gas turbine industry, due to its significant influence on high temperature mechanical properties. This paper reports an experimental investigation and numerical simulation of the SC solidification process of a Ni-based superalloy to study effects of withdrawal rate and starter block size on crystal orientation. The results show that the crystal misorientation of the sample with 40 mm starter block height is decreased with increasing withdrawal rate up to about 9 mm/min, beyond which the amount of misorientation is increased. It was found that the withdrawal rate, height of the starter block and temperature gradient are completely inter-dependent and indeed achieving a SC specimen with a minimum misorientation needs careful optimization of these process parameters. The height of starter block was found to have higher impact on crystal orientation compared to the withdrawal rate. A suitable withdrawal rate regime along with a sufficient starter block height was proposed to produce SC parts with the lowest misorientation.

  4. Long-Term Blocking of Calcium Channels in mdx Mice Results in Differential Effects on Heart and Skeletal Muscle

    DEFF Research Database (Denmark)

    Jørgensen, Louise Helskov; Blain, Alison; Greally, Elizabeth

    2011-01-01

    in older mice. However, streptomycin treatment did not show positive effects in diaphragm or heart muscle, and heart pathology was worsened. Thus, blocking calcium channels even before disease onset does not prevent dystrophy, making this an unlikely treatment for DMD. These findings highlight...

  5. NEUROMUSCULAR AND CARDIOVASCULAR EFFECTS OF NEOSTIGMINE AND METHYL-ATROPINE ADMINISTERED AT DIFFERENT DEGREES OF ROCURONIUM-INDUCED NEUROMUSCULAR BLOCK

    NARCIS (Netherlands)

    VANDENBROEK, L; PROOST, JH; WIERDA, JMKH; NJOO, MD; HENNIS, PJ

    1994-01-01

    The neuromuscular and cardiovascular effects of neostigmine, 40 mug kg-1, and methyl-atropine, 7 mug kg-1, administered at different degrees of rocuronium-induced (600 mug kg-1) neuromuscular block were evaluated. In one group of patients spontaneous recovery was awaited (Group A; n = 20).

  6. Twin Block appliance with acrylic capping does not have a significant inhibitory effect on lower incisor proclination

    NARCIS (Netherlands)

    van der Plas, Mark Cornelis; Janssen, Krista Ingeborg; Pandis, Nikolaos; Livas, Christos

    Objective: To investigate the effect of acrylic capping, treatment duration, overjet, and lower incisor inclination on the posttreatment tooth position in patients treated with 2 Twin Block (TB) appliance versions. Materials and Methods: Cephalograms of 56 patients with Class II malocclusion (21

  7. Block design allowed for control of the Hawthorne effect in a randomized controlled trial of test ordering

    NARCIS (Netherlands)

    Verstappen, Wim H. J. M.; van der Weijden, Trudy; ter Riet, Gerben; Grimshaw, Jeremy; Winkens, Ron; Grol, Richard P. T. M.

    2004-01-01

    Background and Objective: To evaluate the value of balanced incomplete block designs in quality improvement research, and their capacity to control for the Hawthorne effect. Methods: General practitioners teams were randomized into three arms and received an intervention on test ordering, relating

  8. Block design allowed for control of the Hawthorne effect in a randomized controlled trial of test ordering.

    NARCIS (Netherlands)

    Verstappen, W.H.; Weijden, T. van der; Riet, G. ter; Grimshaw, J.; Winkens, R.; Grol, R.P.T.M.

    2004-01-01

    BACKGROUND AND OBJECTIVE: To evaluate the value of balanced incomplete block designs in quality improvement research, and their capacity to control for the Hawthorne effect. METHODS: General practitioners teams were randomized into three arms and received an intervention on test ordering, relating

  9. Neuromodulatory effect of Gαs- or Gαq-coupled G-protein-coupled receptor on NMDA receptor selectively activates the NMDA receptor/Ca2+/calcineurin/cAMP response element-binding protein-regulated transcriptional coactivator 1 pathway to effectively induce brain-derived neurotrophic factor expression in neurons.

    Science.gov (United States)

    Fukuchi, Mamoru; Tabuchi, Akiko; Kuwana, Yuki; Watanabe, Shinjiro; Inoue, Minami; Takasaki, Ichiro; Izumi, Hironori; Tanaka, Ayumi; Inoue, Ran; Mori, Hisashi; Komatsu, Hidetoshi; Takemori, Hiroshi; Okuno, Hiroyuki; Bito, Haruhiko; Tsuda, Masaaki

    2015-04-08

    Although coordinated molecular signaling through excitatory and modulatory neurotransmissions is critical for the induction of immediate early genes (IEGs), which lead to effective changes in synaptic plasticity, the intracellular mechanisms responsible remain obscure. Here we measured the expression of IEGs and used bioluminescence imaging to visualize the expression of Bdnf when GPCRs, major neuromodulator receptors, were stimulated. Stimulation of pituitary adenylate cyclase-activating polypeptide (PACAP)-specific receptor (PAC1), a Gαs/q-protein-coupled GPCR, with PACAP selectively activated the calcineurin (CN) pathway that is controlled by calcium signals evoked via NMDAR. This signaling pathway then induced the expression of Bdnf and CN-dependent IEGs through the nuclear translocation of CREB-regulated transcriptional coactivator 1 (CRTC1). Intracerebroventricular injection of PACAP and intraperitoneal administration of MK801 in mice demonstrated that functional interactions between PAC1 and NMDAR induced the expression of Bdnf in the brain. Coactivation of NMDAR and PAC1 synergistically induced the expression of Bdnf attributable to selective activation of the CN pathway. This CN pathway-controlled expression of Bdnf was also induced by stimulating other Gαs- or Gαq-coupled GPCRs, such as dopamine D1, adrenaline β, CRF, and neurotensin receptors, either with their cognate agonists or by direct stimulation of the protein kinase A (PKA)/PKC pathway with chemical activators. Thus, the GPCR-induced expression of IEGs in coordination with NMDAR might occur via the selective activation of the CN/CRTC1/CREB pathway under simultaneous excitatory and modulatory synaptic transmissions in neurons if either the Gαs/adenylate cyclase/PKA or Gαq/PLC/PKC-mediated pathway is activated. Copyright © 2015 the authors 0270-6474/15/355606-19$15.00/0.

  10. Nanostructure of Solid Precipitates Obtained by Expansion of Polystyrene-block-Polybutadiene Solutions in Near Critical Propane: Block Ratio and Micellar Solution Effects

    Energy Technology Data Exchange (ETDEWEB)

    Green, Jade [University of Wyoming, Laramie; Tyrrell, Zachary [University of Wyoming, Laramie; Radosz, Maciej [University of Wyoming, Laramie; Hong, Kunlun [ORNL; Mays, Jimmy [ORNL

    2011-01-01

    In contrast to incompressible liquid solutions, compressible near-critical solutions of block copolymers allow for controlling rapid structure transformations with pressure alone. For example, when dissolved in near-critical propane, polystyrene-block-polybutadiene can form a random molecular solution at high pressures, a micellar solution at moderate pressures, and a solvent-free precipitate at low pressures. In contrast to the unstructured virgin copolymer, such a propane-treated precipitate rapidly self-assembles toward structures characteristic of equilibrated block copolymers, such as lamellae, spheres, or cylinders, which depend on the block ratio rather than on the decompression rate or temperature, at least within the rate and temperature ranges investigated in this work. At lower temperatures, however, say below 40 C, glass transition of the styrene-butadiene diblocks can inhibit independent structure formation, while crystallization of their hydrogenated-butadiene analogues can preserve the micellar-solution structure.

  11. Self-assembly of poly(vinylidene fluoride–polystyrene block copolymers in solution: Effects of the length of polystyrene block and solvent compositions

    Directory of Open Access Journals (Sweden)

    Yao Wu

    2017-09-01

    Full Text Available We report the first preliminary and extensive study on the solution self-assembly behaviors of poly(vinylidene fluoride–b-polystyrene (PVDF–PS block copolymers. The two PVDF–PS polymers we examined have the same length of PVDF block with number averaged repeating unit of 180, but distinctly different lengths of PS block with number averaged repeating unit of 125 and 1202. The self-assembly experiments were carried out in a series of mixture solutions containing a good solvent N,N-dimethylformamide and a selective solvent with different ratios. Our results showed that the self-assembly process was greatly affected by the two factors we examined, i.e. the length of the PS block and the solvent composition. We hope that our study could stimulate more research on the self-assembly of PVDF-containing polymers in solution.

  12. Effects of Grafting Density on Block Polymer Self-Assembly: From Linear to Bottlebrush

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Tzu-Pin [Division; Chang, Alice B. [Division; Luo, Shao-Xiong [Division; Chen, Hsiang-Yun [Division; Lee, Byeongdu [X-Ray; Grubbs, Robert H. [Division

    2017-09-13

    Grafting density is an important structural parameter that imparts significant influences over the physical properties of architecturally complex polymers. In this report, the physical consequences of varying the grafting density (z) were studied in the context of block polymer self-assembly. Well-defined block polymers spanning the linear, comb, and bottlebrush regimes (0 ≤ z ≤ 1) were prepared via grafting-through ring-opening-metathesis polymer-ization (ROMP). ω-norbornenyl poly(D,L-lactide) (PLA) and polystyrene (PS) macromonomers were copolymerized with discrete co-monomers in different feed ratios, enabling precise control over the grafting density. Small-angle X-ray scattering (SAXS) experiments demonstrate that these graft block polymers can self-assemble into long-range-ordered lamellar structures. For seventeen series of block polymers with variable z, the scal-ing of the lamellar period with the total backbone degree of polymerization (d* ~ Nbbα) was studied. The scaling exponent α monotonically decreases with decreasing z and exhibits an apparent transition at z ≈ 0.2, suggesting significant changes in the chain conformations. Comparison of two block polymer systems, one that is strongly segregated for all z (System I) and one that experiences weak segregation at low z (System II), indicates that the observed trends are primarily caused by the polymer architectures, instead of segregation strengths. A model is pro-posed in which the characteristic ratio (C∞), a proxy for the backbone stiffness, scales with Nbb as a function of the grafting density: C ~ Nbbf(z). To the best of our knowledge, this report represents the first study of scaling behavior for the self-assembly of block polymers with variable grafting density. The relationships disclosed herein provide valuable insights into conformational changes with grafting density, thus introducing new opportunities for future block polymer design.

  13. Potentiation of glycine-gated NR1/NR3A NMDA receptors relieves Ca2+-dependent outward rectification

    Directory of Open Access Journals (Sweden)

    Christian Madry

    2010-03-01

    Full Text Available Glycine has diverse functions within the mammalian central nervous system. It inhibits postsynaptic neurons via strychnine-sensitive glycine receptors (GlyRs and enhances neuronal excitation through co-activation of N-methyl-D-aspartate (NMDA receptors. Classical Ca2+-permeable NMDA receptors are composed of glycine-binding NR1 and glutamate-binding NR2 subunits, and hence require both glutamate and glycine for efficient activation. In contrast, recombinant receptors composed of NR1 and the glycine binding NR3A and/or NR3B subunits lack glutamate binding sites and can be activated by glycine alone. Therefore these receptors are also named excitatory glycine receptors. Co-application of antagonists of the NR1 glycine-binding site or of the divalent cation Zn2+ markedly enhances the glycine responses of these receptors. To gain further insight into the properties of these glycine-gated NMDA receptors, we investigated their current-voltage (I-V dependence. Whole-cell current-voltage relations of glycine currents recorded from NR1/NR3B and NR1/NR3A/NR3B expressing oocytes were found to be linear under our recording conditions. In contrast, NR1/NR3A receptors displayed a strong outwardly rectifying I-V relation. Interestingly, the voltage-dependent inward current block was abolished in the presence of NR1 antagonists, Zn2+ or a combination of both. Further analysis revealed that Ca2+ (1.8 mM present in our recording solutions was responsible for the voltage-dependent inhibition of ion flux through NR1/NR3A receptors. Since physiological concentrations of the divalent cation Mg2+ did not affect the I-V dependence, our data suggest that relief of the voltage-dependent Ca2+ block of NR1/NR3A receptors by Zn2+ may be important for the regulation of excitatory glycinergic transmission, according to the Mg2+-block of conventional NR1/NR2 NMDA receptors.

  14. Glutamatergic dysfunction in catatonia? Successful treatment of three acute akinetic catatonic patients with the NMDA antagonist amantadine.

    OpenAIRE

    Northoff, G; Eckert, J; Fritze, J

    1997-01-01

    Therapeutic efficiacy of the NMDA antagonist amantadine is reported in three acute neuroleptic free akinetic catatonic patients. Intravenous infusion of amantadine led to the resolution of catatonic symptoms and considerable reductions of scores in various motor scales (Simpson Angus scale for extrapyramidal side effects (SEPS), the abnormal involuntary movement scale (AIMS), Rogers catatonia and schizophrenia scales). The therapeutic effect of amantadine showed a characteristic temporal patt...

  15. The effect of heat treatment on the internal structure of nanostructured block copolymer films

    DEFF Research Database (Denmark)

    Sepe, Alessandro; Hoppe, E T; Jaksch, S

    2011-01-01

    We report on the temperature dependence of the nanostructure of thin block copolymer films, as studied using in situ grazing-incidence small-angle x-ray scattering (GISAXS). We focus on spin-coated poly(styrene-b-butadiene) diblock copolymer thin films featuring lamellae perpendicular to the subs......We report on the temperature dependence of the nanostructure of thin block copolymer films, as studied using in situ grazing-incidence small-angle x-ray scattering (GISAXS). We focus on spin-coated poly(styrene-b-butadiene) diblock copolymer thin films featuring lamellae perpendicular...

  16. Neuroprotection by NMDA receptor antagonists in a variety of neuropathologies.

    Science.gov (United States)

    Palmer, G C

    2001-09-01

    Because of adverse reactions, early efforts to introduce high affinity competitive or use-dependent NMDA receptor antagonists into patients suffering from stroke, head trauma or epilepsy met with failure. Later it was discovered that both low affinity use-dependent NMDA receptor antagonists and compounds with selective affinity for the NR2B receptor subunit met the criteria for safe administration into patients. Furthermore, these low affinity antagonists exhibit significant mechanistic differences from their higher affinity counterparts. Success of the latter is attested to the ability of the following low affinity compounds to be marketed: 1) Cough suppressant-dextromethorphan (available for decades); 2) Parkinson's disease--amantadine, memantine and budipine; 3) Dementia--memantine; and 4) Epilepsy--felbamate. Moreover, Phase III clinical trials are ongoing with remacemide for epilepsy and Huntington's disease and head trauma for HU-211. A host of compounds are or were under evaluation for the possible treatment of stroke, head trauma, hyperalgesia and various neurodegenerative disorders. Despite the fact that other drugs with associated NMDA receptor mechanisms have reached clinical status, this review focuses only on those competitive and use-dependent NMDA receptor antagonists that reached clinical trails. The ensuing discussions link the in vivo pharmacological investigations that led to the success/mistakes/ failures for eventual testing of promising compounds in the clinic.

  17. The meth brain: methamphetamines alter brain functions via NMDA receptors

    Czech Academy of Sciences Publication Activity Database

    Proft, Juliane; Weiss, Norbert

    2015-01-01

    Roč. 34, č. 1 (2015), s. 1-3 ISSN 0231-5882 R&D Projects: GA ČR GA15-13556S Institutional support: RVO:61388963 Keywords : ion channel * methamphetamine * piriform cortex * NMDA receptor * AMPA receptor Subject RIV: CE - Biochemistry Impact factor: 0.892, year: 2015

  18. Adult forebrain NMDA receptors gate social motivation and social memory.

    Science.gov (United States)

    Jacobs, Stephanie; Tsien, Joe Z

    2017-02-01

    Motivation to engage in social interaction is critical to ensure normal social behaviors, whereas dysregulation in social motivation can contribute to psychiatric diseases such as schizophrenia, autism, social anxiety disorders and post-traumatic stress disorder (PTSD). While dopamine is well known to regulate motivation, its downstream targets are poorly understood. Given the fact that the dopamine 1 (D1) receptors are often physically coupled with the NMDA receptors, we hypothesize that the NMDA receptor activity in the adult forebrain principal neurons are crucial not only for learning and memory, but also for the proper gating of social motivation. Here, we tested this hypothesis by examining sociability and social memory in inducible forebrain-specific NR1 knockout mice. These mice are ideal for exploring the role of the NR1 subunit in social behavior because the NR1 subunit can be selectively knocked out after the critical developmental period, in which NR1 is required for normal development. We found that the inducible deletion of the NMDA receptors prior to behavioral assays impaired, not only object and social recognition memory tests, but also resulted in profound deficits in social motivation. Mice with ablated NR1 subunits in the forebrain demonstrated significant decreases in sociability compared to their wild type counterparts. These results suggest that in addition to its crucial role in learning and memory, the NMDA receptors in the adult forebrain principal neurons gate social motivation, independent of neuronal development. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Investigation of the effect of dorsal penile block to penile tissue.

    Science.gov (United States)

    Boybeyi, Özlem; Gunal, Yasemin Dere; Atasoy, Pınar; Kısa, Ucler; Aslan, Mustafa Kemal

    2015-10-01

    Dorsal penile block (DPB) is a frequently used technique for regional anesthesia, but the effect of DPB on penile tissue has not been reported so far. An experimental study was conducted to evaluate the acute effects of DPB on penile tissue. Eighteen male rats were included and randomly assigned to three groups. No intervention was made in the control group (CG, n = 6). In the sham group (SG, n = 6) 1 ml normal saline, and in DPB group (PBG, n = 6) 1 ml of 0.25% bupivacaine without adrenaline (0.5 mg/kg), was infused with a 30 mm, 23 gauge needle. DPB was performed by inserting the needle in the midline when pulling down the penis and directing the needle to the 11 and 1 o'clock positions. Another puncture was done at the midline on the ventral side and the remaining drug was infused slowly. The penile tissues were harvested for biochemical (malonyldialdehyde: MDA; nitric oxide: NO; superoxide dismutase: SOD) and histopathological examination. Histopathological assessments were made of inflammation, edema and fibrosis; epithelial degradation in the urethra; vascular obliteration in periurethral tissue; and the peripheral nerve cells. Concentrations of NO and SOD were significantly decreased in the PBG compared with the CG and SG (p PBG compared with the CG and SG (p 0.05). In hematoxylin and eosin stain samples, vascular structures of the corpus cavernosa were slightly decreased in number in the SG and PBG compared with the CG, but that difference was not statistically significant (p > 0.05). The S-100 staining was significantly higher in the PBG and SG compared with the CG (p PBG (p < 0.05). DPB causes alteration in oxidative stress markers because of an unknown effect. Although the results revealed increased inflammatory reaction in penile tissue after DPB, they are not enough to suggest not using bupivacaine for DPB in clinical practice. Although DPB does not cause any major histopathological alteration, it results in an increase in inflammatory response in the

  20. Controversial Effects of D-Amino Acid Oxidase Activator (DAOA/G72 on D-Amino Acid Oxidase (DAO Activity in Human Neuronal, Astrocyte and Kidney Cell Lines: The N-methyl D-aspartate (NMDA Receptor Hypofunction Point of View

    Directory of Open Access Journals (Sweden)

    Vinita Jagannath

    2017-10-01

    Full Text Available Dysfunction of D-amino acid oxidase (DAO and DAO activator (DAOA/G72 genes have been linked to neuropsychiatric disorders. The glutamate hypothesis of schizophrenia has proposed that increased DAO activity leads to decreased D-serine, which subsequently may lead to N-methyl-D-aspartate (NMDA receptor hypofunction. It has been shown that DAOA binds to DAO and increases its activity. However, there are also studies showing DAOA decreases DAO activity. Thus, the effect of DAOA on DAO is controversial. We aimed to understand the effect of DAOA on DAO activity in neuron-like (SH-SY5Y, astrocyte-like (1321N1 and kidney-like (HEK293 human cell lines. DAO activity was measured based on the release of hydrogen peroxide and its interaction with Amplex Red reagent. We found that DAOA increases DAO activity only in HEK293 cells, but has no effect on DAO activity in SH-SY5Y and 1321N1 cells. This might be because of different signaling pathways, or due to lower DAO and DAOA expression in SH-SY5Y and 1321N1 cells compared to HEK293 cells, but also due to different compartmentalization of the proteins. The lower DAO and DAOA expression in neuron-like SH-SY5Y and astrocyte-like 1321N1 cells might be due to tightly regulated expression, as previously reported in the human post-mortem brain. Our simulation experiments to demonstrate the interaction between DAOA and human DAO (hDAO showed that hDAO holoenzyme [hDAO with flavine adenine dinucleotide (FAD] becomes more flexible and misfolded in the presence of DAOA, whereas DAOA had no effect on hDAO apoprotein (hDAO without FAD, which indicate that DAOA inactivates hDAO holoenzyme. Furthermore, patch-clamp analysis demonstrated no effect of DAOA on NMDA receptor activity in NR1/NR2A HEK293 cells. In summary, the interaction between DAO and DAOA seems to be cell type and its biochemical characteristics dependent which still needs to be elucidated.

  1. Controversial Effects of D-Amino Acid Oxidase Activator (DAOA)/G72 on D-Amino Acid Oxidase (DAO) Activity in Human Neuronal, Astrocyte and Kidney Cell Lines: The N-methyl D-aspartate (NMDA) Receptor Hypofunction Point of View.

    Science.gov (United States)

    Jagannath, Vinita; Brotzakis, Zacharias Faidon; Parrinello, Michele; Walitza, Susanne; Grünblatt, Edna

    2017-01-01

    Dysfunction of D-amino acid oxidase ( DAO ) and DAO activator ( DAOA )/ G72 genes have been linked to neuropsychiatric disorders. The glutamate hypothesis of schizophrenia has proposed that increased DAO activity leads to decreased D-serine, which subsequently may lead to N-methyl-D-aspartate (NMDA) receptor hypofunction. It has been shown that DAOA binds to DAO and increases its activity. However, there are also studies showing DAOA decreases DAO activity. Thus, the effect of DAOA on DAO is controversial. We aimed to understand the effect of DAOA on DAO activity in neuron-like (SH-SY5Y), astrocyte-like (1321N1) and kidney-like (HEK293) human cell lines. DAO activity was measured based on the release of hydrogen peroxide and its interaction with Amplex Red reagent. We found that DAOA increases DAO activity only in HEK293 cells, but has no effect on DAO activity in SH-SY5Y and 1321N1 cells. This might be because of different signaling pathways, or due to lower DAO and DAOA expression in SH-SY5Y and 1321N1 cells compared to HEK293 cells, but also due to different compartmentalization of the proteins. The lower DAO and DAOA expression in neuron-like SH-SY5Y and astrocyte-like 1321N1 cells might be due to tightly regulated expression, as previously reported in the human post-mortem brain. Our simulation experiments to demonstrate the interaction between DAOA and human DAO (hDAO) showed that hDAO holoenzyme [hDAO with flavine adenine dinucleotide (FAD)] becomes more flexible and misfolded in the presence of DAOA, whereas DAOA had no effect on hDAO apoprotein (hDAO without FAD), which indicate that DAOA inactivates hDAO holoenzyme. Furthermore, patch-clamp analysis demonstrated no effect of DAOA on NMDA receptor activity in NR1/NR2A HEK293 cells. In summary, the interaction between DAO and DAOA seems to be cell type and its biochemical characteristics dependent which still needs to be elucidated.

  2. Parity effects in the scaling of block entanglement in gapless spin chains

    NARCIS (Netherlands)

    Calabrese, P.; Campostrini, M.; Essler, F.; Nienhuis, B.

    2010-01-01

    We consider the Rényi α entropies for Luttinger liquids (LL). For large block lengths ℓ, these are known to grow like lnℓ. We show that there are subleading terms that oscillate with frequency 2kF (the Fermi wave number of the LL) and exhibit a universal power-law decay with ℓ. The new critical

  3. Templated Self-Assembly of Block Copolymers: Effect on Substrate Topography

    NARCIS (Netherlands)

    Cheng, Joy Y.; Ross, C.A.; Thomas, Edwin L.; Smith, Henry I.; Vancso, Gyula J.

    2003-01-01

    Topographical confinement is used to template the formation of nanoscale domains in a self-assembled block copolymer film. The topographical template controls the row spacings and feature dimensions of the copolymer and can deliberately introduce defects in the arrays (see Figure). For example, a

  4. Concentration effect on tuning of block copolymer-mediated synthesis of gold nanoparticles.

    Science.gov (United States)

    Ray, Debes; Aswal, V K; Srivastava, D

    2010-10-01

    Synthesis of gold nanoparticles has been examined using triblock copolymer Pluronic P85 (EO26PO39EO26) at different concentrations as a function of hydrogen tetrachloroaureate (III) hydrate (HAuCl4 x 3H2O) in aqueous solution. The concentration of P85 block copolymer was varied from 0.5 to 2 wt% at fixed temperature (30 degrees C) in presence of HAuCl4 x 3H2O in the range of 0.002 to 0.2 wt% for each P85 concentration. The surface plasmon resonance in the time-dependent UV-visible spectra reveals that increase in the block copolymer concentration increases the yield of the gold nanoparticles but decreases their stability. Both small-angle neutron scattering (SANS) and dynamic light scattering (DLS) show that the number density of block copolymer micelles increase almost linearly with the concentration, which is related to result in higher numbers of nucleation centers and therefore increase in the yield of gold nanoparticles. The fact that increase in the number density of nanoparticles also increases the chances of aggregation and this tends to decrease the stability at higher block copolymer concentration. Transmission electron microscopy (TEM) images confirm the larger sizes of the nanoparticles formed in these systems at higher concentrations.

  5. Nanoparticle-cell interactions: surface chemistry effects on the cellular uptake of biocompatible block copolymer assemblies

    Czech Academy of Sciences Publication Activity Database

    de Castro, C. E.; Ribeiro, C. A. S.; Alavarse, A. C.; Albuquerque, L. J. C.; da Silva, M. C. C.; Jäger, Eliezer; Surman, František; Schmidt, V.; Giacomelli, C.; Giacomelli, F. C.

    2018-01-01

    Roč. 34, č. 5 (2018), s. 2180-2188 ISSN 0743-7463 R&D Projects: GA ČR(CZ) GA17-09998S Institutional support: RVO:61389013 Keywords : biocompatibility * block copolymers * controlled drug delivery Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 3.833, year: 2016

  6. Block Rate Pricing of Water in Indonesia : An Analysis of Welfare Effects

    NARCIS (Netherlands)

    Rouwendal, J.; Rietveld, P.; Zwart, B.

    2000-01-01

    Block rate pricing of piped water in Indonesian cities has a progressive structure: the marginal price paid increases with the volume of demand. This paper estimates household water demand in Salatiga city using the Burtless and Hausman model, and finds that its distribution is not unimodal—that

  7. Power To Detect Additive Treatment Effects with Randomized Block and Analysis of Covariance Designs.

    Science.gov (United States)

    Klockars, Alan J.; Potter, Nina Salcedo; Beretvas, S. Natasha

    1999-01-01

    Compared the power of analysis of covariance (ANCOVA) and two types of randomized block designs as a function of the correlation between the concomitant variable and the outcome measure, the number of groups, the number of participants, and nominal power. Discusses advantages of ANCOVA. (Author/SLD)

  8. Comparison of clinical effects of ultrasound guided suprascapular nerve block and oral pregabalin versus suprascapular nerve block alone for pain relief in frozen shoulder

    Directory of Open Access Journals (Sweden)

    Pratik Kumar Mitra

    2016-01-01

    Full Text Available Introduction: Frozen shoulder is a painful and disabling condition in patients in 40-70 years age group , affecting 2-5% of general population. Aim of the study was to assess pain relief and functional improvement after supracapular nerve block with or without pregabalin, in patients with diagnosed case of frozen shoulder who failed to respond to medical treatment for 3 months. Material and methods: 100 patients with unilateral frozen shoulder was divided into two equal groups (n = 50 in a randomized double blind protocol. Group A (n = 50 received three doses of suprascapular nerve block and oral pregabalin 75 mg at bed time daily while Group B (n = 50 received suprascapular nerve block and oral placebo tablets in a similar way. Suprascapular nerve block was given with Inj depot methyl prednisolone acetate 1 ml (40 mg + 9 ml 0.25% inj bupivacine for three successive weeks with ultrasound. Patients were followed up at 4 th , 6 th and 12 th week after injection. Visual Analogue Scale (VAS was used to assess intensity of pain and range of movement estimated using goniometer in terms of abduction, external rotation and internal rotation in sitting position. Results: Results showed Group-A patients had almost complete pain relief and significant improvement in the range of movement at the end of 12 th week compared to Group B (P < 0.05. Conclusion: Combination therapy of suprascapular nerve block and oral pregabalin 75 mg is better for patients with frozen shoulder compare to suprascapular nerve block only.

  9. Prevention of the adverse photic effects of peripheral light-focusing using UV-blocking contact lenses.

    Science.gov (United States)

    Kwok, L Stephen; Kuznetsov, Valerian A; Ho, Arthur; Coroneo, Minas T

    2003-04-01

    Peripheral light-focusing (PLF) is an occult form of ultraviolet radiation (UVR) hazardous to the human eye. In PLF, obliquely incident light is refracted from the peripheral cornea to concentrated sites inside the anterior segment. In the current study, the directionality of this phenomenon for UVR and whether PLF is established in outdoor settings exposed to sunlight were investigated. The protection provided by a UV-blocking contact lens was also evaluated. UVA and UVB sensors were placed on the nasal limbus of an anatomically based model eye. The temporal limbus was exposed to a UV light source placed at various angles behind the frontal plane. PLF was quantified with the sensor output. The ensemble was mounted in the orbit of a mannequin head and exposed to sunlight in three insolation environments within the region of Sydney, Australia. PLF for UVA and UVB was determined with no eyewear or with sunglasses and commercially available soft contact lenses, with and without UV-blocking capability. The intensity of UVA peaked at approximately 120 degrees incidence, the level at which the UVB response was also at its maximum. The intensification of UVA was up to x18.3. The intensity of PLF for UVA and UVB was reduced by an order of magnitude by a UV-blocking contact lens, whereas a clear contact lenses had a much lesser effect. Only the UV-blocking contact lens achieved a significant effect on UVA and UVB irradiance in the urban, beach, and mountain locales (P UV-blocking soft contact lenses. Sunglasses may be unable to shield oblique rays, unless side protection is incorporated. Contact lenses can offer UVR protection against all angles of incidence, including the peak-response angle. They can also protect the eye in settings in which the wearing of sunglasses is not feasible or convenient.

  10. Effect of Phase Change Materials (PCMs Integrated into a Concrete Block on Heat Gain Prevention in a Hot Climate

    Directory of Open Access Journals (Sweden)

    Ahmad Hasan

    2016-10-01

    Full Text Available In the current study, a phase change material (PCM contained in an insulated concrete block is tested in extremely hot weather in the United Arab Emirates (UAE to evaluate its cooling performance. An insulated chamber is constructed behind the block containing PCM to mimic a scaled down indoor space. The effect of placement of the PCM layer on heat gain indoors is studied at two locations: adjacent to the outer as well as the inner concrete layer. The inclusion of PCM reduced heat gain through concrete blocks compared to blocks without PCM, yielding a drop in cooling load indoors. The placement of PCM and insulation layers adjacent to indoors exhibited better cooling performance compared to that adjacent to the outdoors. In the best case, a temperature drop of 8.5% and a time lag of 2.6 h are achieved in peak indoor temperature, rendering a reduction of 44% in the heat gain. In the tested hot climate, the higher ambient temperature and the lower wind speed hampered heat dissipation and PCM re-solidification by natural ventilation. The findings recommend employing a mechanical ventilation in hot climates to enhance regeneration of the PCM to solid state for its optimal performance.

  11. Effect of Total Dose of Lidocaine on Duration of Adductor Canal Block, Assessed by Different Test Methods

    DEFF Research Database (Denmark)

    Jæger, Pia; Koscielniak-Nielsen, Zbigniew J; Hilsted, Karen Lisa

    2016-01-01

    BACKGROUND: The binary aims of this study were to investigate the effect of total dose of lidocaine on duration of an adductor canal block (ACB) and to validate different methods used to assess nerve blocks. METHODS: We performed 2 blinded, randomized, controlled crossover trials, including healthy......, young men. In study 1, 14 subjects received 4 ACBs with saline and 40, 80, and 160 mg lidocaine. In study 2, 14 new subjects received 2 ACBs with 100 and 300 mg lidocaine. We kept volume constant at 20 mL for all blocks, only altering concentration. ACB duration was assessed every hour postblock using......: In study 1, block duration assessed by mechanical discrimination differed significantly when comparing the 40-mg dose with the 80-mg dose (mean difference, 1.15 hours; 99% confidence interval [CI], 0.38–2.09 hours) and with the 160-mg dose (mean difference, 0.92 ours; 99% CI, 0.17–1.62). However...

  12. Expert evaluation of technical documentation 'Analysis of structures of blocks 1-6 of the Kozloduy NPP for the seismic effect of local earthquakes'

    International Nuclear Information System (INIS)

    Jurukovski, D.

    1999-01-01

    The subject of this expert evaluation is the technical documentation 'Analysis of structures of blocks 1-6 of the Kozloduy NPP for the seismic effect of local earthquakes'. It includes reviews of expert evaluations of the parameters of local seismic effects and the analysis of floor response spectra for blocks 3, 4, 5 and 6 at Kozloduy NPP

  13. Regulated internalization of NMDA receptors drives PKD1-mediated suppression of the activity of residual cell-surface NMDA receptors.

    Science.gov (United States)

    Fang, Xiao-Qian; Qiao, Haifa; Groveman, Bradley R; Feng, Shuang; Pflueger, Melissa; Xin, Wen-Kuan; Ali, Mohammad K; Lin, Shuang-Xiu; Xu, Jindong; Duclot, Florian; Kabbaj, Mohamed; Wang, Wei; Ding, Xin-Sheng; Santiago-Sim, Teresa; Jiang, Xing-Hong; Salter, Michael W; Yu, Xian-Min

    2015-11-19

    Constitutive and regulated internalization of cell surface proteins has been extensively investigated. The regulated internalization has been characterized as a principal mechanism for removing cell-surface receptors from the plasma membrane, and signaling to downstream targets of receptors. However, so far it is still not known whether the functional properties of remaining (non-internalized) receptor/channels may be regulated by internalization of the same class of receptor/channels. The N-methyl-D-aspartate receptor (NMDAR) is a principal subtype of glutamate-gated ion channel and plays key roles in neuronal plasticity and memory functions. NMDARs are well-known to undergo two types of regulated internalization - homologous and heterologous, which can be induced by high NMDA/glycine and DHPG, respectively. In the present work, we investigated effects of regulated NMDAR internalization on the activity of residual cell-surface NMDARs and neuronal functions. In electrophysiological experiments we discovered that the regulated internalization of NMDARs not only reduced the number of cell surface NMDARs but also caused an inhibition of the activity of remaining (non-internalized) surface NMDARs. In biochemical experiments we identified that this functional inhibition of remaining surface NMDARs was mediated by increased serine phosphorylation of surface NMDARs, resulting from the activation of protein kinase D1 (PKD1). Knockdown of PKD1 did not affect NMDAR internalization but prevented the phosphorylation and inhibition of remaining surface NMDARs and NMDAR-mediated synaptic functions. These data demonstrate a novel concept that regulated internalization of cell surface NMDARs not only reduces the number of NMDARs on the cell surface but also causes an inhibition of the activity of remaining surface NMDARs through intracellular signaling pathway(s). Furthermore, modulating the activity of remaining surface receptors may be an effective approach for treating receptor

  14. Summary of an Investigation into the Relative Effects on Student Performance on a "Block" vs. a "Non-Block" Scheduled Developmental Semester: Pretest-Posttest Control Group Design.

    Science.gov (United States)

    Baylis, Clifford A., Jr.

    In fall 1980, a block scheduled developmental semester was offered for the first time at the Boyce Campus of the Community College of Allegheny County. The program was composed of three integrated courses: "Man, Time, and Social Change," a social science elective; "Basic Writing Techniques," a developmental English course; and…

  15. N-Methyl-D-aspartic Acid (NMDA in the nervous system of the amphioxus Branchiostoma lanceolatum

    Directory of Open Access Journals (Sweden)

    Garcia-Fernàndez Jordi

    2007-12-01

    Full Text Available Abstract Background NMDA (N-methyl-D-aspartic acid is a widely known agonist for a class of glutamate receptors, the NMDA type. Synthetic NMDA elicits very strong activity for the induction of hypothalamic factors and hypophyseal hormones in mammals. Moreover, endogenous NMDA has been found in rat, where it has a role in the induction of GnRH (Gonadotropin Releasing Hormone in the hypothalamus, and of LH (Luteinizing Hormone and PRL (Prolactin in the pituitary gland. Results In this study we show evidence for the occurrence of endogenous NMDA in the amphioxus Branchiostoma lanceolatum. A relatively high concentration of NMDA occurs in the nervous system of this species (3.08 ± 0.37 nmol/g tissue in the nerve cord and 10.52 ± 1.41 nmol/g tissue in the cephalic vesicle. As in rat, in amphioxus NMDA is also biosynthesized from D-aspartic acid (D-Asp by a NMDA synthase (also called D-aspartate methyl transferase. Conclusion Given the simplicity of the amphioxus nervous and endocrine systems compared to mammalian, the discovery of NMDA in this protochordate is important to gain insights into the role of endogenous NMDA in the nervous and endocrine systems of metazoans and particularly in the chordate lineage.

  16. The effect of block copolymer structure on the internalization of polymeric micelles by human breast cancer cells.

    Science.gov (United States)

    Mahmud, Abdullah; Lavasanifar, Afsaneh

    2005-10-10

    The objective of this study was to assess the effect of hydrophilic/hydrophobic block chain lengths on the internalization of poly(ethylene oxide)-block-poly(epsilon-caprolactone) (PEO-b-PCL) micelles by cancer cells. PEO-b-PCL block copolymers with varied PEO and PCL chain lengths were synthesized, assembled to polymeric micelles and loaded with a hydrophobic fluorescent probe (DiI) through a co-solvent evaporation method of physical encapsulation. The slow release of the fluorescent probe from the micellar structure was evidenced following DiI transfer to lipid vesicles. The extent of micellar uptake by cancer cells was investigated through their incubation with MCF-7 cells followed by measurement of the fluorescent emission intensity of DiI (lambda=550 nm) in separated lysed cells. Cellular internalization of polymeric micelles was confirmed by laser scanning microscopy. The mechanism of micellar uptake was investigated by pretreatment of MCF-7 cells with chlorpromazine and cytochalasin B. Encapsulation of DiI in PEO-b-PCL micelles lowered the extent and rate of hydrophobic probe internalization by cancer cells. For polymeric micelles with 5000 gmol(-1) of PCL and varied PEO molecular weights of 2000, 5000 and 13,000 gmol(-1), maximum uptake was observed at a PEO molecular weight of 5000 gmol(-1). For polymeric micelles with 5000 gmol(-1) of PEO and varied PCL molecular weights of 5000, 13,000 and 24,000 gmol(-1), maximum uptake was observed at 13,000 gmol(-1) of PCL. Chlorpromazine reduced the cellular uptake of PEO-b-PCL micelles independent from the block copolymer structure, pointing to the involvement of clathrin mediated endocytosis mechanisms in the uptake of polymeric micelles by cancer cells. Inhibition of cellular uptake of PEO-b-PCL micelles by cytochalasin B, on the other hand, was found to be dependent on the chemical structure of the core/shell forming blocks.

  17. Rat intra-hippocampal NMDA infusion induces cell-specific damage and changes in expression of NMDA and GABAA receptor subunits.

    Science.gov (United States)

    Rambousek, Lukas; Kleteckova, Lenka; Kubesova, Anna; Jirak, Daniel; Vales, Karel; Fritschy, Jean-Marc

    2016-06-01

    Excessive stimulation of NMDA receptors with glutamate or other potent agonists such as NMDA leads to excitotoxicity and neural injury. In this study, we aimed to provide insight into an animal model of brain excitotoxic damage; single unilateral infusion of NMDA at mild dose into the hippocampal formation. NMDA infusion induced chronic, focal neurodegeneration in the proximity of the injection site. The lesion was accompanied by severe and progressive neuroinflammation and affected preferentially principal neurons while sparing GABAergic interneurons. Furthermore, the unilateral lesion did not cause significant impairment of spatial learning abilities. Finally, GluN1 and GluN2B subunits of NMDA receptor were significantly upregulated up to 3 days after the NMDA infusion, while GABAA α5 subunit was downregulated at 30 days after the lesion. Taken together, a single infusion of NMDA into the hippocampal formation represents an animal model of excitotoxicity-induced chronic neurodegeneration of principal neurons accompanied by severe neuroinflammation and subunit specific changes in NMDA and GABAA receptors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Contribution of orientational effects into radiation-chemical properties of segregated block copolymers

    International Nuclear Information System (INIS)

    Bol'bit, N.M.; Korneev, Yu.N.

    1992-01-01

    Model of radiolysis of microphase-separated block copolymers of PS with PB is proposed. According this scheme the radiation-chemical yields of paramagnetic centres and crosslinks in PB domains differ from those for the PB homopolymer by the value proportional to the fraction of ordered chain segments. This orientational small-scale order arises as a result of the deformation of chains in a domain in the direction perpendicular to the interphase

  19. NMDA receptors on non-dopaminergic neurons in the VTA support cocaine sensitization.

    Directory of Open Access Journals (Sweden)

    Yu Luo

    2010-08-01

    Full Text Available The initiation of behavioral sensitization to cocaine and other psychomotor stimulants is thought to reflect N-methyl-D-aspartate receptor (NMDAR-mediated synaptic plasticity in the mesolimbic dopamine (DA circuitry. The importance of drug induced NMDAR mediated adaptations in ventral tegmental area (VTA DA neurons, and its association with drug seeking behaviors, has recently been evaluated in Cre-loxp mice lacking functional NMDARs in DA neurons expressing Cre recombinase under the control of the endogenous dopamine transporter gene (NR1(DATCre mice.Using an additional NR1(DATCre mouse transgenic model, we demonstrate that while the selective inactivation of NMDARs in DA neurons eliminates the induction of molecular changes leading to synaptic strengthening, behavioral measures such as cocaine induced locomotor sensitization and conditioned place preference remain intact in NR1(DATCre mice. Since VTA DA neurons projecting to the prefrontal cortex and amygdala express little or no detectable levels of the dopamine transporter, it has been speculated that NMDA receptors in DA neurons projecting to these brain areas may have been spared in NR1(DATCre mice. Here we demonstrate that the NMDA receptor gene is ablated in the majority of VTA DA neurons, including those exhibiting undetectable DAT expression levels in our NR1(DATCre transgenic model, and that application of an NMDAR antagonist within the VTA of NR1(DATCre animals still blocks sensitization to cocaine.These results eliminate the possibility of NMDAR mediated neuroplasticity in the different DA neuronal subpopulations in our NR1(DATCre mouse model and therefore suggest that NMDARs on non-DA neurons within the VTA must play a major role in cocaine-related addictive behavior.

  20. NMDA receptor glycine modulatory site in the ventral tegmental area regulates the acquisition, retrieval, and reconsolidation of cocaine reward memory.

    Science.gov (United States)

    Zhou, Shuang-jiang; Xue, Li-fen; Wang, Xue-yi; Jiang, Wen-gao; Xue, Yan-xue; Liu, Jian-feng; He, Yin-yin; Luo, Yi-xiao; Lu, Lin

    2012-05-01

    Accumulating clinical and preclinical studies have shown that the memories of the rewarding effects of drugs and their paired cues may contribute to relapse and persistent cocaine use. Glutaminergic actions in the ventral tegmental area (VTA) have been shown to regulate the rewarding effect of drugs and conditioned responses to drug-associated cues, but the role of the VTA in the acquisition, retrieval, and reconsolidation of cocaine cues is not yet known. In the present study, we used 7-chlorothiokynurenic acid (7-CTKA), an N-methyl-D-aspartate (NMDA) receptor glycine modulatory site antagonist with no rewarding effects, to examine the role of the NMDA receptor glycine modulatory site in the acquisition, retrieval, and reconsolidation of cocaine-related reward memory using the conditioned place preference (CPP) paradigm. Separate groups of Sprague-Dawley rats were trained to acquire cocaine-induced CPP. Vehicle or 7-CTKA was microinjected into the VTA or substantia nigra (SN) (5 μg/μl) at different time points: 10 min before each CPP training session (acquisition), 10 min before the reactivation of CPP (retrieval), and immediately after the reactivation of CPP (reconsolidation). Cocaine-induced CPP was retested 24 h and 1 and 2 weeks after 7-CTKA administration. 7-CTKA microinjected into the VTA, but not SN, significantly impaired the acquisition, retrieval, and reconsolidation of cocaine-induced CPP without affecting cocaine-induced locomotion. Our findings suggest that the NMDA receptor glycine modulatory site in the VTA plays a major role in cocaine reward memory, and NMDA receptor glycine site antagonists may be potential pharmacotherapies for the management of relapse.

  1. PSD-95 uncoupling from NMDA receptors by Tat-N-dimer ameliorates neuronal depolarisation in cortical spreading depression

    DEFF Research Database (Denmark)

    Kucharz, Krzysztof; Søndergaard Rasmussen, Ida; Bach, Anders

    2017-01-01

    Cortical spreading depression is associated with activation of NMDA receptors, which interact with the postsynaptic density protein 95 (PSD-95) that binds to nitric oxide synthase (nNOS). Here, we tested whether inhibition of the nNOS/PSD-95/NMDA receptor complex formation by anti-ischemic compound......, UCCB01-144 (Tat-N-dimer) ameliorates the persistent effects of cortical spreading depression on cortical function. Using in vivo two-photon microscopy in somatosensory cortex in mice, we show that fluorescently labelled Tat-N-dimer readily crosses blood-brain barrier and accumulates in nerve cells...... during the first hour after i.v. injection. The Tat-N-dimer suppressed stimulation-evoked synaptic activity by 2-20%, while cortical blood flow and cerebral oxygen metabolic (CMRO2) responses were preserved. During cortical spreading depression, the Tat-N-dimer reduced the average amplitude...

  2. Ghrelin upregulates the phosphorylation of the GluN2B subunit of the NMDA receptor by activating GHSR1a and Fyn in the rat hippocampus.

    Science.gov (United States)

    Berrout, Liza; Isokawa, Masako

    2018-01-01

    Ghrelin and its receptor GHSR1a have been shown to exert numerous physiological functions in the brain, in addition to the well-established orexigenic role in the hypothalamus. Earlier work indicated that ghrelin stimulated the phosphorylation of the GluN1 subunit of the NMDA receptor (NMDAR) and enhanced synaptic transmission in the hippocampus. In the present study, we report that the exogenous application of ghrelin increased GluN2B phosphorylation. This increase was independent of GluN2B subunit activity or NMDAR channel activity. However, it depended on the activation of GHSR1a and Fyn as it was blocked by D-Lys3-GHRP-6 and PP2, respectively. Inhibitors for G-protein-regulated second messengers, such as Rp-cAMP, H89, TBB, ryanodine, and thapsigargin, unexpectedly enhanced GluN2B phosphorylation, suggesting that cAMP, PKA, casein kinase II, and cytosolic calcium signaling may oppose to the effect of ghrelin on the phosphorylation of GluN2B. Our findings suggest that 1) GluN2B is likely a molecular target of ghrelin and GHSR1a-driven signaling cascades, and 2) the ghrelin-mediated phosphorylation of GluN2B depends on Fyn activation under complex negative regulation by other second messengers. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. [The effects of transversus abdominis plane block on analgesic and anesthetic consumption during total abdominal hysterectomy: a randomized controlled study].

    Science.gov (United States)

    Karaman, Tugba; Ozsoy, Asker Zeki; Karaman, Serkan; Dogru, Serkan; Tapar, Hakan; Sahin, Aynur; Dogru, Hatice; Suren, Mustafa

    2018-04-06

    A transversus abdominis plane block is a peripheral block method that has been used successfully for pain relief after total abdominal hysterectomy. However, the effects of the combination of the transversus abdominis plane block and general anesthesia on analgesic and anesthetic requirements remain unclear. This randomized placebo-controlled study is aimed to evaluate the effects of transversus abdominis plane block on analgesic and anesthetic consumption during total abdominal hysterectomy under general anesthesia. Sixty-six women undergoing total abdominal hysterectomy were randomized into two groups to receive general anesthesia alone (control group) or with transversus abdominis plane block using 20mL of 0.25% bupivacaine (transversus abdominis plane group). Intraoperative remifentanil and sevoflurane consumption were recorded. We also evaluated the postoperative pain, nausea, quality of recovery scores and rescue analgesic requirement during postoperative 24hours. The total remifentanil and sevoflurane consumption is significantly lower in transversus abdominis plane group; respectively mean (SD) 0.130 (0.25) vs. 0.094 (0.02) mcg.kg -1 .min -1 ; p<0.01 and 0.295 (0.05) vs. 0.243 (0.06) mL.min -1 ; p<0.01. In the postoperative period, pain scores were significantly reduced in transversus abdominis plane group soon after surgery; median (range) 6 (2-10) vs. 3 (0-5); p<0.001, at 2h (5 [3-9] vs. 2.5 [0-6]; p<0.001), at 6h (4 [2-7] vs. 3[0-6], p<0.001), at 12h (3.5 [1-6] vs. 2 [1-5]; p=0.003). The patients in the transversus abdominis plane group had significantly higher QoR-40 scores 190.5 (175-197) vs. 176.5 (141-187); p<0.001). Combining transversus abdominis plane block with general anesthesia can provide reduced opioid and anesthetic consumption and can improve postoperative pain and quality of recovery scores in patients undergoing total abdominal hysterectomy. Copyright © 2018 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All

  4. Bonding effectiveness of self-adhesive and conventional-type adhesive resin cements to CAD/CAM resin blocks. Part 2: Effect of ultrasonic and acid cleaning.

    Science.gov (United States)

    Kawaguchi, Asuka; Matsumoto, Mariko; Higashi, Mami; Miura, Jiro; Minamino, Takuya; Kabetani, Tomoshige; Takeshige, Fumio; Mine, Atsushi; Yatani, Hirofumi

    2016-01-01

    The present study assessed the effect of ultrasonic and acid cleaning on resin cement bonding to CAD/CAM resin blocks. One of two resin cements, PANAVIA V5 (PV5) or PANAVIA SA CEMENT HANDMIX (PSA), were bonded to one of 24 CAD/CAM blocks (KATANA AVENCIA BLOCK). Each cement group was divided into four subgroups: no cleaning (Ctl), ultrasonic cleaning (Uc), acid cleaning (Ac) and Uc+Ac. Micro-tensile bond strengths (µTBSs) were measured immediately and 1, 3, and 6 months after water storage. Block surfaces after each treatment were analyzed by scanning electron microscopy. Analysis of variance revealed a statistically significant effect for the parameters 'surface treatment' (p<0.001, F=40), 'resin cement' (p<0.001, F=696) and 'water aging' (p<0.001, F=71). The PV5 group exhibited higher µTBS values than the PSA group. Although cleaning after sandblasting was effective in removing residual alumina particles, it did not affect the long-term bonding durability with non-contaminated CAD/CAM resin blocks.

  5. Competitive (AP7) and non-competitive (MK-801) NMDA receptor antagonists differentially alter glucose utilization in rat cortex

    International Nuclear Information System (INIS)

    Clow, D.W.; Lee, S.J.; Hammer, R.P. Jr.

    1991-01-01

    The effects of D,L-2-amino-7-phosphonoheptanoic acid (AP7), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, and MK-801, a non-competitive NMDA receptor antagonist, on regional brain metabolism were studied in unanesthetized, freely moving rats by using the quantitative 14 C2-deoxyglucose autoradiographic procedure. AP7 (338 or 901 mg/kg) produced a dose-dependent decrease of metabolic activity throughout most of the regions studied including sensory, motor, and limbic cortices. In contrast, MK-801 (0.1 or 1.0 mg/kg) resulted in a dose-dependent decrease of metabolic activity in sensory cortices, and an increase in limbic regions such as the hippocampal stratum lacunosum moleculare and entorhinal cortex. MK-801 also produced a biphasic response in agranular motor cortex, whereby the low dose increased while the high dose decreased labeling. In addition, MK-801 produced heterogeneous effects on regional cerebral metabolism in sensory cortices. Metabolic activity decreased in layer IV relative to layer Va following MK-801 treatment in primary somatosensory (SI) and visual (VI) cortices, suggesting a shift in activity from afferent fibers innervating layer IV to those innervating layer Va. MK-801 administration also decreased metabolic activity in granular SI relative to dysgranular SI, and in VI relative to secondary visual cortex (VII), thus providing a relative sparing of activity in dysgranular SI and VII. Thus, the non-competitive NMDA receptor antagonist suppressed activity from extrinsic neocortical sources, enhancing relative intracortical activity and stimulating limbic regions, while the competitive NMDA antagonist depressed metabolic activity in all cortical regions

  6. Competitive (AP7) and non-competitive (MK-801) NMDA receptor antagonists differentially alter glucose utilization in rat cortex

    Energy Technology Data Exchange (ETDEWEB)

    Clow, D.W.; Lee, S.J.; Hammer, R.P. Jr. (Department of Anatomy and Reproductive Biology, School of Medicine, University of Hawaii, Honolulu (USA))

    1991-04-01

    The effects of D,L-2-amino-7-phosphonoheptanoic acid (AP7), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, and MK-801, a non-competitive NMDA receptor antagonist, on regional brain metabolism were studied in unanesthetized, freely moving rats by using the quantitative {sup 14}C2-deoxyglucose autoradiographic procedure. AP7 (338 or 901 mg/kg) produced a dose-dependent decrease of metabolic activity throughout most of the regions studied including sensory, motor, and limbic cortices. In contrast, MK-801 (0.1 or 1.0 mg/kg) resulted in a dose-dependent decrease of metabolic activity in sensory cortices, and an increase in limbic regions such as the hippocampal stratum lacunosum moleculare and entorhinal cortex. MK-801 also produced a biphasic response in agranular motor cortex, whereby the low dose increased while the high dose decreased labeling. In addition, MK-801 produced heterogeneous effects on regional cerebral metabolism in sensory cortices. Metabolic activity decreased in layer IV relative to layer Va following MK-801 treatment in primary somatosensory (SI) and visual (VI) cortices, suggesting a shift in activity from afferent fibers innervating layer IV to those innervating layer Va. MK-801 administration also decreased metabolic activity in granular SI relative to dysgranular SI, and in VI relative to secondary visual cortex (VII), thus providing a relative sparing of activity in dysgranular SI and VII. Thus, the non-competitive NMDA receptor antagonist suppressed activity from extrinsic neocortical sources, enhancing relative intracortical activity and stimulating limbic regions, while the competitive NMDA antagonist depressed metabolic activity in all cortical regions.

  7. Neuroprotection Against NMDA Induced Cell Death in Rat Nucleus Basalis by Ca2+ Antagonist Nimodipine, Influence of Aging and Developmental Drug Treatment

    NARCIS (Netherlands)

    Luiten, P.G.M.; Douma, B.R.K.; Zee, E.A. van der; Nyakas, C.

    In the current study the neuroprotective effect of the L-type calcium channel antagonist nimodipine in rat brain was investigated in N-methyl-D-aspartate-induced neuronal degeneration in vivo. In the present model NMDA was unilaterally injected in the magnocellular nucleus basalis and the neurotoxic

  8. The metabotropic glutamate receptor agonist 1S,3R-ACPD stimulates and modulates NMDA receptor mediated excitotoxicity in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Blaabjerg, M; Kristensen, Bjarne Winther; Bonde, C

    2001-01-01

    The potential toxic effects of the metabotropic glutamate receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) and its interactions with the N-methyl-D-aspartate (NMDA) receptor were studied in hippocampal brain slice cultures, using densitometric measurements of the cellular...

  9. The hemodynamic effects of spinal block with low dose of bupivacaine and sufentanil in patients with low myocardial ejection fraction.

    Directory of Open Access Journals (Sweden)

    Mehdi Sanatkar

    2013-07-01

    Full Text Available The aim of this study was to assess the effect of spinal block with low dose of bupivacaine and sufentanil on patients with low cardiac output who underwent lower limb surgery. Fifteen patients who had ejection fraction less than 40% (group 1 were compared with 65 cases with ejection fraction more than 40% (group 2 in our study. Our subjects underwent spinal block with 7.5 mg hyperbaric bupivacaine 0.5% and 5 µg sufentanil. We recorded early events such as hypotension, bradycardia, vasopressor need and ST segment change in our cases. The average mean arterial pressure decreased 13% (110 mmHg to 95.7 mmHg in group 1 and 20% (160 mmHg to 128 mmHg in group 2 (P<0.001. Hypotension due to spinal anesthesia was observed in none of our subjects in both groups and none of our cases need to vasopressor support. All patients remained alert, and no ST segment changes were observed in two groups. In our study none of subjects complained of pain intraoperatively. The subjects were without complaints during the spinal anesthetic in both groups. Spinal block with low dose local anesthetic and sufentanil was a safe and effective method for lower limb surgery in patients with low ejection fraction.

  10. The effect of blue-blocking and neutral intraocular lenses on circadian photoentrainment and sleep one year after cataract surgery

    DEFF Research Database (Denmark)

    Brøndsted, Adam Elias; Haargaard, Birgitte; Sander, Birgit

    2017-01-01

    PURPOSE: To compare the long-term effect on circadian photoentrainment and sleep in patients implanted with neutral and blue-blocking intraocular lenses 1 year after cataract surgery. METHODS: Randomized, controlled trial involving 67 patients with age-related cataract. Intervention was cataract......; the latter was also used to determine objective sleep quality. The Pittsburgh Sleep Quality Index determined subjective sleep quality. RESULTS: One year after surgery, peak melatonin concentration was 3.3 pg/ml (95% CI, 2-5.5) corresponding to 50% lower for the participants allocated to blue-blocking IOLs...... compared with participants allocated to neutral IOLs. Compared with preoperative levels, the ipRGC response had increased by 13.7% (95% confidence interval [CI], 3.2-22.6) 1 year after surgery. Objective sleep quality was also improved as the time of wakefulness after sleep onset had improved by 5 min (95...

  11. Rheological characterization of nanostructured material based on Polystyrene-b-poly(ethylene-butylene)-b-polystyrene (SEBS) block copolymer: Effect of block copolymer composition and nanoparticle geometry

    OpenAIRE

    Hasanabadi, Noushin; Nazockdast, Hossein; Balog, Sandor; Lattuada, Marco

    2017-01-01

    Block copolymer (BCP) nanocomposite systems are of broad interest; however, reports on the role of nanoparticles on microphase separation behavior are rare. The goal of present study is to investigate the preparation of composite nanostructured materials containing Multi-Walled Carbon Nanotubes (MWCNTs) or graphene nanoplates. BCP nanocomposites based on the linear triblock copolymer, Polystyrene-b-poly(ethylene-butylene)-b-polystyrene (SEBS), with different morphological structure were...

  12. Clinical safety and effectiveness of transversus abdominis plane (TAP) block in post-operative analgesia: a systematic review and meta-analysis.

    Science.gov (United States)

    Ma, Ning; Duncan, Joanna K; Scarfe, Anje J; Schuhmann, Susanne; Cameron, Alun L

    2017-06-01

    Transversus abdominis plane (TAP) blocks can provide analgesia postoperatively for a range of surgeries. Abundant clinical trials have assessed TAP block showing positive analgesic effects. This systematic review assesses safety and effectiveness outcomes of TAP block in all clinical settings, comparing with both active (standard care) and inactive (placebo) comparators. PubMed, EMBASE, The Cochrane Library and the University of York CRD databases were searched. RCTs were screened for their eligibility and assessed for risk of bias. Meta-analyses were performed on available data. TAP block showed an equivalent safety profile to all comparators in the incidence of nausea (OR = 1.07) and vomiting (OR = 0.81). TAP block was more effective in reducing morphine consumption [MD = 13.05, 95% CI (8.33, 51.23)] and in delaying time to first analgesic request [MD = 123.49, 95% CI (48.59, 198.39)]. Postoperative pain within 24 h was reduced or at least equivalent in TAP block compared to its comparators. Therefore, TAP block is a safe and effective procedure compared to standard care, placebo and other analgesic techniques. Further research is warranted to investigate whether the TAP block technique can be improved by optimizing dose and technique-related factors.

  13. Differential Modulation of GABAA and NMDA Receptors by an α7-nicotinic Acetylcholine Receptor Agonist in Chronic Glaucoma

    Directory of Open Access Journals (Sweden)

    Xujiao Zhou

    2017-12-01

    Full Text Available Presynaptic modulation of γ-aminobutyric acid (GABA release by an alpha7 nicotinic acetylcholine receptor (α7-nAChR agonist promotes retinal ganglion cell (RGC survival and function, as suggested by a previous study on a chronic glaucomatous model from our laboratory. However, the role of excitatory and inhibitory amino acid receptors and their interaction with α7-nAChR in physiological and glaucomatous events remains unknown. In this study, we investigated GABAA and N-methyl-D-aspartate (NMDA receptor activity in control and glaucomatous retinal slices and the regulation of amino acid receptor expression and function by α7-nAChR. Whole-cell patch-clamp recordings from RGCs revealed that the α7-nAChR specific agonist PNU-282987 enhanced the amplitude of currents elicited by GABA and reduced the amplitude of currents elicited by NMDA. The positive modulation of GABAA receptor and the negative modulation of NMDA receptor (NMDAR by PNU-282987-evoked were prevented by pre-administration of the α7-nAChR antagonist methyllycaconitine (MLA. The frequency and the amplitude of glutamate receptor-mediated miniature glutamatergic excitatory postsynaptic currents (mEPSCs were not significantly different between the control and glaucomatous RGCs. Additionally, PNU-282987-treated slices showed no alteration in the frequency or amplitude of mEPSCs relative to control RGCs. Moreover, we showed that expression of the α1 subunit of the GABAA receptor was downregulated and the expression of the NMDAR NR2B subunit was upregulated by intraocular pressure (IOP elevation, and the changes of high IOP were blocked by PNU-282987. In conclusion, retina GABAA and NMDARs are modulated positively and negatively, respectively, by activation of α7-nAChR in in vivo chronic glaucomatous models.

  14. The delayed strengthening of synaptic connectivity in the amygdala depends on NMDA receptor activation during acute stress.

    Science.gov (United States)

    Yasmin, Farhana; Saxena, Kapil; McEwen, Bruce S; Chattarji, Sumantra

    2016-10-01

    There is growing evidence that stress leads to contrasting patterns of structural plasticity in the hippocampus and amygdala, two brain areas implicated in the cognitive and affective symptoms of stress-related psychiatric disorders. Acute stress has been shown to trigger a delayed increase in the density of dendritic spines in the basolateral amygdala (BLA) of rodents. However, the physiological correlates of this delayed spinogenesis in the BLA remain unexplored. Furthermore, NMDA receptors (NMDARs) have been known to underlie chronic stress-induced structural plasticity in the hippocampus, but nothing is known about the role of these receptors in the delayed spinogenesis, and its physiological consequences, in the BLA following acute stress. Here, using whole-cell recordings in rat brain slices, we find that a single exposure to 2-h immobilization stress enhances the frequency, but not amplitude, of miniature excitatory postsynaptic currents (mEPSCs) recorded from principal neurons in the BLA 10 days later. This was also accompanied by faster use-dependent block of NMDA receptor currents during repeated stimulation of thalamic inputs to the BLA, which is indicative of higher presynaptic release probability at these inputs 10 days later. Furthermore, targeted in vivo infusion of the NMDAR-antagonist APV into the BLA during the acute stress prevents the increase in mEPSC frequency and spine density 10 days later. Together, these results identify a role for NMDARs during acute stress in both the physiological and morphological strengthening of synaptic connectivity in the BLA in a delayed fashion. These findings also raise the possibility that activation of NMDA receptors during stress may serve as a common molecular mechanism despite the divergent patterns of plasticity that eventually emerge after stress in the amygdala and hippocampus. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological

  15. Structure, function, and pharmacology of NMDA receptor channels

    Czech Academy of Sciences Publication Activity Database

    Vyklický, Vojtěch; Kořínek, Miloslav; Smejkalová, Tereza; Balík, Aleš; Krausová, Barbora; Kaniaková, Martina; Lichnerová, Katarina; Černý, Jiří; Krůšek, Jan; Dittert, Ivan; Horák, Martin; Vyklický ml., Ladislav

    2014-01-01

    Roč. 63, Suppl.1 (2014), S191-S203 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP303/11/0075; GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GAP303/12/1464; GA ČR(CZ) GPP303/11/P391; GA TA ČR(CZ) TE01020028; GA MŠk(CZ) EE2.3.30.0025; GA MŠk(CZ) ED1.1.00/02.0109 EU Projects: European Commission(XE) SalmandNmda 276827 Grant - others:Univerzita Karlova(CZ) 800313 Program:FP7 Institutional support: RVO:67985823 Keywords : glutamate receptor * NMDA receptor * ion Channel Subject RIV: ED - Physiology Impact factor: 1.293, year: 2014

  16. Mechanistic Insights into Xenon Inhibition of NMDA Receptors from MD Simulations

    OpenAIRE

    Liu, Lu Tian; Xu, Yan; Tang, Pei

    2010-01-01

    Inhibition of N-methyl-D-aspartate (NMDA) receptors has been viewed as a primary cause of xenon anesthesia, yet the mechanism is unclear. Here, we investigated interactions between xenon and the ligand-binding domain (LBD) of a NMDA receptor and examined xenon-induced structural and dynamical changes that are relevant to functional changes of the NMDA receptor. Several comparative molecular dynamics simulations were performed on two X-ray structures representing the open- and closed-cleft LBD...

  17. Blockade of NMDA receptors decreased spinal microglia activation in bee venom induced acute inflammatory pain in rats.

    Science.gov (United States)

    Li, Li; Wu, Yongfang; Bai, Zhifeng; Hu, Yuyan; Li, Wenbin

    2017-03-01

    Microglial cells in spinal dorsal horn can be activated by nociceptive stimuli and the activated microglial cells release various cytokines enhancing the nociceptive transmission. However, the mechanisms underlying the activation of spinal microglia during nociceptive stimuli have not been well understood. In order to define the role of NMDA receptors in the activation of spinal microglia during nociceptive stimuli, the present study was undertaken to investigate the effect of blockade of NMDA receptors on the spinal microglial activation induced by acute peripheral inflammatory pain in rats. The acute inflammatory pain was induced by subcutaneous bee venom injection to the plantar surface of hind paw of rats. Spontaneous pain behavior, thermal withdrawal latency and mechanical withdrawal threshold were rated. The expression of specific microglia marker CD11b/c was assayed by immunohistochemistry and western blot. After bee venom treatment, it was found that rats produced a monophasic nociception characterized by constantly lifting and licking the injected hind paws, decreased thermal withdrawal latency and mechanical withdrawal threshold; immunohistochemistry displayed microglia with enlarged cell bodies, thickened, extended cellular processes with few ramifications, small spines, and intensive immunostaining; western blot showed upregulated expression level of CD11b/c within the period of hyperalgesia. Prior intrathecal injection of MK-801, a selective antagonist of NMDA receptors, attenuated the pain behaviors and suppressed up-regulation of CD11b/c induced by bee venom. It can be concluded that NMDA receptors take part in the mediation of spinal microglia activation in bee venom induced peripheral inflammatory pain and hyperalgesia in rats.

  18. The Effect of Bisphasic Calcium Phosphate Block Bone Graft Materials with Polysaccharides on Bone Regeneration.

    Science.gov (United States)

    Yoo, Hyun-Sang; Bae, Ji-Hyeon; Kim, Se-Eun; Bae, Eun-Bin; Kim, So-Yeun; Choi, Kyung-Hee; Moon, Keum-Ok; Jeong, Chang-Mo; Huh, Jung-Bo

    2017-01-01

    In this study, bisphasic calcium phosphate (BCP) and two types of polysaccharide, carboxymethyl cellulose (CMC) and hyaluronic acid (HyA), were used to fabricate composite block bone grafts, and their physical and biological features and performances were compared and evaluated in vitro and in vivo. Specimens of the following were prepared as 6 mm diameter, 2 mm thick discs; BPC mixed with CMC (the BCP/CMC group), BCP mixed with crosslinked CMC (the BCP/c-CMC group) and BCP mixed with HyA (the BCP/HyA group) and a control group (specimens were prepared using particle type BCP). A scanning electron microscope study, a compressive strength analysis, and a cytotoxicity assessment were conducted. Graft materials were implanted in each of four circular defects of 6 mm diameter in calvarial bone in seven rabbits. Animals were sacrificed after four weeks for micro-CT and histomorphometric analyses, and the findings obtained were used to calculate new bone volumes (mm³) and area percentages (%). It was found that these two values were significantly higher in the BCP/c-CMC group than in the other three groups ( p block bone graft material incorporating crosslinked CMC has potential utility when bone augmentation is needed.

  19. The Effect of Bisphasic Calcium Phosphate Block Bone Graft Materials with Polysaccharides on Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Hyun-Sang Yoo

    2017-01-01

    Full Text Available In this study, bisphasic calcium phosphate (BCP and two types of polysaccharide, carboxymethyl cellulose (CMC and hyaluronic acid (HyA, were used to fabricate composite block bone grafts, and their physical and biological features and performances were compared and evaluated in vitro and in vivo. Specimens of the following were prepared as 6 mm diameter, 2 mm thick discs; BPC mixed with CMC (the BCP/CMC group, BCP mixed with crosslinked CMC (the BCP/c-CMC group and BCP mixed with HyA (the BCP/HyA group and a control group (specimens were prepared using particle type BCP. A scanning electron microscope study, a compressive strength analysis, and a cytotoxicity assessment were conducted. Graft materials were implanted in each of four circular defects of 6 mm diameter in calvarial bone in seven rabbits. Animals were sacrificed after four weeks for micro-CT and histomorphometric analyses, and the findings obtained were used to calculate new bone volumes (mm3 and area percentages (%. It was found that these two values were significantly higher in the BCP/c-CMC group than in the other three groups (p < 0.05. Within the limitations of this study, BCP composite block bone graft material incorporating crosslinked CMC has potential utility when bone augmentation is needed.

  20. The Level of NMDA Receptor in the Membrane Modulates Amyloid-β Association and Perforation.

    Science.gov (United States)

    Peters, Christian; Sepúlveda, Fernando J; Fernández-Pérez, Eduardo J; Peoples, Robert W; Aguayo, Luis G

    2016-05-06

    Alzheimer's disease is a neurodegenerative disorder that affects mostly the elderly. The main histopathological markers are the senile plaques formed by amyloid-β peptide (Aβ) aggregates that can perforate the plasma membrane of cells, increasing the intracellular calcium levels and releasing synaptic vesicles that finally lead to a delayed synaptic failure. Several membrane proteins and lipids interact with Aβ affecting its toxicity in neurons. Here, we focus on NMDA receptors (NMDARs) as proteins that could be modulating the association and neurotoxic perforation induced by Aβ on the plasma membrane. In fact, our results showed that decreasing NMDARs, using enzymatic or siRNA approaches, increased the association of Aβ to the neurons. Furthermore, overexpression of NMDARs also resulted in an enhanced association between NMDA and Aβ. Functionally, the reduction in membrane NMDARs augmented the process of membrane perforation. On the other hand, overexpressing NMDARs had a protective effect because Aβ was now unable to cause membrane perforation, suggesting a complex relationship between Aβ and NMDARs. Because previous studies have recognized that Aβ oligomers are able to increase membrane permeability and produce amyloid pores, the present study supports the conclusion that NMDARs play a critical protective role on Aβ actions in hippocampal neurons. These results could explain the lack of correlation between brain Aβ burden and clinically observed dementia.

  1. Preclinical anxiolytic profiles of 7189 and 8319, novel non-competitive NMDA antagonists

    International Nuclear Information System (INIS)

    Dunn, R.W.; Corbett, R.; Martin, L.L.; Payack, J.F.; Laws-Ricker, L.; Wilmot, C.A.; Rush, D.K.; Cornfeldt, M.L.; Fielding, S.

    1990-01-01

    Antagonists at excitatory amino acid receptors, especially the N-methyl-d-aspartate (NMDA) subtype, have been shown to possess anticonvulsant and anxiolytic properties. Two closely related benzeneethanamines, are potential novel anxiolytic agents which bind with high affinity to the NMDA receptor at the non-competitive site and are relatively non-toxic (LD50's-160 mg/kg, ip). 7189 and 8319 showed anxiolytic effects in schedule controlled conflict assays as well as in the social interaction (SI) and elevated plus maze (EPM) procedures in rats. Following intraperitoneal administration of 7189 at 20 to 60 mg/kg, conflict responding was increased from 2- to 7-fold in the modified Cook and Davidson and Geller conflict paradigms. 8319, at 2.5 to 5 mg/kg, produced a two fold increase in conflict responding. In the non-schedule controlled procedures, 7189 at 20 mg/kg increased SI time by 23% while in the EPM at 10 to 20 mg/kg, open arm exploration time increased by 41 to 77%. Likewise, 8319 at 2.5 and 5 mg/kg increased open arm exploration and SI time by 50 and 37%, respectively. In summary, 7189 and 8319 were efficacious in four behavioral procedures predictive of potential anxiolytic agents. Although these compounds have not been submitted for clinical evaluation, they may represent a new class of beneficial compounds for the treatment of anxiety

  2. Gel phantom study of a cryosurgical probe with a thermosiphon effect and liquid nitrogen-cooled aluminum thermal storage blocks.

    Science.gov (United States)

    Isoda, Haruo; Takehara, Yasuo; Fujino, Hitoshi; Sone, Kazuya; Suzuki, Takeshi; Tsuzaki, Yoshinari; Miyazaki, Kouji; Fujie, Michio; Sakahara, Harumi; Maekawa, Yasuaki

    2015-08-01

    Cryosurgery is a minimally invasive treatment for certain types of cancers. Argon-based cryosurgical devices are available at present, however a large compressed gas cylinder with the pressure of 300 atmospheres is needed. To overcome these drawbacks, we developed a new cryosurgical probe measuring about 50 cm in length with separate lumens inside for liquid and gaseous ethylene to be used as a thermosiphon and liquid nitrogen-cooled aluminum thermal storage blocks. The probe needle was 8 cm in length and 3 mm in outer diameter. To investigate the freezing capabilities of our new cryosurgical system we inserted the needle 5cm into a poly-acrylamide gel phantom warmed to 36.5 ℃. Thermal storage blocks made of aluminum, cooled at -196 ℃ in liquid nitrogen, were attached to the condenser of the probe and replaced with thermal storage blocks every 4 to 5 minutes to compensate for warming. We took digital camera images of the ice ball at the needle and measured the temperature in certain locations of the cryoprobe. Ice ball formation started at one minute after cooling. The sizes (longest diameter × minimum diameter) at 10, 20 and 30 minutes after the start of the procedure were 4.5×2.1, 4.5×3.1 and 4.6×3.7 cm, respectively. During the procedure the minimum temperature of the condenser was -85 ℃ and the needle was -65 ℃. This newly developed compact cryosurgical probe with thermosiphon effect and cooled thermal storage blocks created an ice ball that can be used for cryosurgery within 20 minutes.

  3. Timing-dependent reduction in ethanol sedation and drinking preference by NMDA receptor co-agonist d-serine.

    Science.gov (United States)

    Lockridge, Amber; Romero, Gabriel; Harrington, Justin; Newland, Brett; Gong, Zi; Cameron, Andrew; Yuan, Li-Lian

    2012-06-01

    NMDA receptors become a major contributor to acute ethanol intoxication effects at high concentrations as ethanol binds to a unique site on the receptor and inhibits glutamatergic activity in multiple brain areas. Although a convincing body of literature exists on the ability of NMDA receptor antagonists to mimic and worsen cellular and behavioral ethanol effects, receptor agonists have been less well-studied. In addition to a primary agonist site for glutamate, the NMDA receptor contains a separate co-agonist site that responds to endogenous amino acids glycine and d-serine. d-serine is both selective for this co-agonist site and potent in boosting NMDA dependent activity even after systemic administration. In this study, we hypothesized that exogenous d-serine might ameliorate some acute ethanol behaviors by opposing NMDA receptor inhibition. We injected adult male C57 mice with a high concentration of d-serine at various time windows relative to ethanol administration and monitored sedation, motor coordination and voluntary ethanol drinking. d-serine (2.7 g/kg, ip) prolonged latency to a loss of righting reflex (LoRR) and shortened LoRR duration when given 15 min before ethanol (3 g/kg) but not when it was injected with or shortly after ethanol. Blood samples taken at sedative recovery and at fixed time intervals revealed no effect of d-serine on ethanol concentration but an ethanol-induced decrease in l-serine and glycine content was prevented by acute d-serine pre-administration. d-serine had no effect on ethanol-induced (2 g/kg) rotarod deficits in young adult animals but independently and interactively degraded motor performance in a subset of older mice. Finally, a week-long series of daily ip injections resulted in a 50% decrease in free choice ethanol preference for d-serine treated animals compared to saline-injected controls in a two-bottle choice experiment. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Effect of dexmedetomidine as adjuvant in ropivacaine-induced supraclavicular brachial plexus block: A prospective, double-blinded and randomized controlled study

    Directory of Open Access Journals (Sweden)

    Anjan Das

    2014-01-01

    Full Text Available Background and Aims: Different additives have been used to prolong brachial plexus block. We evaluated the effect of adding dexmedetomidine to ropivacaine for supraclavicular brachial plexus blockade. The primary endpoints were the onset and duration of sensory and motor block and duration of analgesia. Materials and Methods: A total of 84 patients (20-50 years posted for elective forearm and hand surgery under supraclavicular brachial plexus block were divided into two equal groups (Group R and RD in a randomized, double-blind fashion. In group RD (n = 42 30 ml 0.5% ropivacaine +1 ml (100 μg of dexmedetomidine and group R (n = 42 30 ml 0.5% ropivacaine +1 ml normal saline were administered in supraclavicular block. Sensory and motor block onset times and block durations, time to first analgesic use, total analgesic need, postoperative visual analog scale (VAS, hemodynamics and side-effects were recorded for each patient. Results: Though with similar demographic profile in both groups, sensory and motor block in group RD (P < 0.05 was earlier than group R. Sensory and motor block duration and time to first analgesic use were significantly longer and the total need for rescue analgesics was lower in group RD (P < 0.05 than group R. Post-operative VAS value at 12 h were significantly lower in group RD (P < 0.05. Intra-operative hemodynamics were significantly lower in group RD (P < 0.05 without any appreciable side-effects. Conclusion: It can be concluded that adding dexmedetomidine to supraclavicular brachial plexus block increases the sensory and motor block duration and time to first analgesic use, and decreases total analgesic use with no side-effects.

  5. Aniracetam, 1-BCP and cyclothiazide differentially modulate the function of NMDA and AMPA receptors mediating enhancement of noradrenaline release in rat hippocampal slices.

    Science.gov (United States)

    Pittaluga, A; Bonfanti, A; Arvigo, D; Raiteri, M

    1999-04-01

    Aniracetam, 1-(1,3-benzodioxol-5-yl-carbonyl)piperidine (1-BCP) and cyclothiazide, three compounds considered to enhance cognition through modulation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors, were evaluated in the 'kynurenate test', a biochemical assay in which some nootropics have been shown to prevent the antagonism by kynurenic acid of the N-methyl-D-aspartate (NMDA)-evoked [3H]noradrenaline ([3H]NA) release from rat hippocampal slices. Aniracetam attenuated the kynurenate (100 microM) antagonism of the [3H]NA release elicited by 100 microM NMDA with high potency (EC50aniracetam, respectively. The effect of aniracetam persisted in the presence of the AMPA receptor antagonist 6-nitro-7-sulphamoyl-benzo[f]quinoxaline-2,3-dione (NBQX) added at 5 microM, a concentration that did not affect NMDA receptors; in contrast, NBQX reduced the effect of 1-BCP and abolished that of cyclothiazide. The AMPA-evoked release of [3H]NA from hippocampal slices or synaptosomes was enhanced by cyclothiazide, less potently by 1-BCP and weakly by aniracetam. High concentrations of kynurenate (1 mM) antagonized the AMPA-evoked [3H]NA release in slices; this antagonism was attenuated by 1 microM cyclothiazide and reversed to an enhancement of AMPA-evoked [3H]NA release by 10 microM of the drug, but was insensitive to 1-BCP or aniracetam. It is concluded that aniracetam exerts a dual effect on glutamatergic transmission: modulation of NMDA receptor function at nanomolar concentrations, and modulation of AMPA receptors at high micromolar concentrations. As to cyclothiazide and 1-BCP, our data concur with the idea that both compounds largely act through AMPA receptors, although an NMDA component may be involved in the effect of 1-BCP.

  6. Toward the development of effective transmission-blocking vaccines for malaria.

    Science.gov (United States)

    Nikolaeva, Daria; Draper, Simon J; Biswas, Sumi

    2015-05-01

    The continued global burden of malaria can in part be attributed to a complex lifecycle, with both human hosts and mosquito vectors serving as transmission reservoirs. In preclinical models of vaccine-induced immunity, antibodies to parasite sexual-stage antigens, ingested in the mosquito blood meal, can inhibit parasite survival in the insect midgut as judged by ex vivo functional studies such as the membrane feeding assay. In an era of renewed political momentum for malaria elimination and eradication campaigns, such observations have fueled support for the development and implementation of so-called transmission-blocking vaccines. While leading candidates are being evaluated using a variety of promising vaccine platforms, the field is also beginning to capitalize on global '-omics' data for the rational genome-based selection and unbiased characterization of parasite and mosquito proteins to expand the candidate list. This review covers the progress and prospects of these recent developments.

  7. Blocking negative effects of senescence in human skin fibroblasts with a plant extract.

    Science.gov (United States)

    Lämmermann, Ingo; Terlecki-Zaniewicz, Lucia; Weinmüllner, Regina; Schosserer, Markus; Dellago, Hanna; de Matos Branco, André Dargen; Autheried, Dominik; Sevcnikar, Benjamin; Kleissl, Lisa; Berlin, Irina; Morizot, Frédérique; Lejeune, Francois; Fuzzati, Nicola; Forestier, Sandra; Toribio, Alix; Tromeur, Anaïs; Weinberg, Lionel; Higareda Almaraz, Juan Carlos; Scheideler, Marcel; Rietveld, Marion; El Ghalbzouri, Abdoel; Tschachler, Erwin; Gruber, Florian; Grillari, Johannes

    2018-01-01

    There is increasing evidence that senescent cells are a driving force behind many age-related pathologies and that their selective elimination increases the life- and healthspan of mice. Senescent cells negatively affect their surrounding tissue by losing their cell specific functionality and by secreting a pro-tumorigenic and pro-inflammatory mixture of growth hormones, chemokines, cytokines and proteases, termed the senescence-associated secretory phenotype (SASP). Here we identified an extract from the plant Solidago virgaurea subsp. alpestris , which exhibited weak senolytic activity, delayed the acquisition of a senescent phenotype and induced a papillary phenotype with improved functionality in human dermal fibroblasts. When administered to stress-induced premature senescent fibroblasts, this extract changed their global mRNA expression profile and particularly reduced the expression of various SASP components, thereby ameliorating the negative influence on nearby cells. Thus, the investigated plant extract represents a promising possibility to block age-related loss of tissue functionality.

  8. Effect of Curing Mode on Shear Bond Strength of Self-Adhesive Cement to Composite Blocks

    Directory of Open Access Journals (Sweden)

    Jin-Young Kim

    2016-03-01

    Full Text Available To overcome the disadvantages of computer-aided design/computer-aided manufacturing (CAD/CAM processed indirect restorations using glass-ceramics and other ceramics, resin nano ceramic, which has high strength and wear resistance with improved polish retention and optical properties, was introduced. The purpose of this study was to evaluate the shear bond strength and fracture pattern of indirect CAD/CAM composite blocks cemented with two self-etch adhesive cements with different curing modes. Sand-blasted CAD/CAM composite blocks were cemented using conventional resin cement, Rely X Ultimate Clicker (RXC, 3M ESPE, St. Paul, MN, USA with Single Bond Universal (SB, 3M ESPE, St. Paul, MN, USA for the control group or two self-adhesive resin cements: Rely X U200 (RXU, 3M ESPE, St. Paul, MN, USA and G-CEM Cerasmart (GC, GC corporation, Tokyo, Japan. RXU and GC groups included different curing modes (light-curing (L and auto-curing (A. Shear bond strength (SBS analyses were performed on all the specimens. The RXC group revealed the highest SBS and the GC A group revealed the lowest SBS. According to Tukey’s post hoc test, the RXC group showed a significant difference compared to the GC A group (p < 0.05. For the curing mode, RXU A and RXU L did not show any significant difference between groups and GC A and GC L did not show any significant difference either. Most of the groups except RXC and RXU L revealed adhesive failure patterns predominantly. The RXC group showed a predominant cohesive failure pattern in their CAD/CAM composite, LavaTM Ultimate (LU, 3M ESPE, St. Paul, MN, USA. Within the limitations of this study, no significant difference was found regarding curing modes but more mixed fracture patterns were showed when using the light-curing mode than when using the self-curing mode.

  9. [Pharmacokinetic and clinical effects of two bupivacaine concentrations on axillary brachial plexus block].

    Science.gov (United States)

    Ferraro, Leonardo H C; Takeda, Alexandre; Barreto, Cleber N; Faria, Bernadete; Assunção, Nilson A

    The risk of systemic bupivacaine toxicity is a persistent problem, which makes its pharmacokinetic study fundamental for regional anesthesia safety. There is little evidence of its influence on plasma peak at different concentrations. The present study compares two bupivacaine concentrations to establish how the concentration affects this drug plasma peak in axillary brachial plexus block. Postoperative latency and analgesia were also compared. 30 patients were randomized. In the 0.25% Group, 0.25% bupivacaine (10mL) was injected per nerve. In the 0.5% Group, 0.5% bupivacaine (5mL) was injected per nerve. Peripheral blood samples were collected during the first 2hours after the blockade. For sample analyses, high performance liquid chromatography mass spectrometry was used. Plasma peak occurred 45minutes after the blockade, with no difference between groups at the assessed time-points. Plasma peak was 933.97 ± 328.03 ng.mL -1 (mean ± SD) in 0.25% Group and 1022.79 ± 253.81 ng.mL -1 in 0.5% Group (p = 0.414). Latency was lower in 0.5% Group than in 0.25% Group (10.67 ± 3.71 × 17.33min ± 5.30, respectively, p = 0.004). No patient had pain within the first 4hours after the blockade. For axillary brachial plexus block, there was no difference in bupivacaine plasma peak despite the use of different concentrations with the same local anesthetic mass. The concentration inversely influenced latency. Copyright © 2017. Publicado por Elsevier Editora Ltda.

  10. Sound production treatment for acquired apraxia of speech: Effects of blocked and random practice on multisyllabic word production.

    Science.gov (United States)

    Wambaugh, Julie; Nessler, Christina; Wright, Sandra; Mauszycki, Shannon; DeLong, Catharine

    2016-10-01

    This study was designed to examine the effects of practice schedule, blocked vs random, on outcomes of a behavioural treatment for acquired apraxia of speech (AOS), Sound Production Treatment (SPT). SPT was administered to four speakers with chronic AOS and aphasia in the context of multiple baseline designs across behaviours and participants. Treatment was applied to multiple sound errors within three-to-five syllable words. All participants received both practice schedules: SPT-Random (SPT-R) and SPT-Blocked (SPT-B). Improvements in accuracy of word production for trained items were found for both treatment conditions for all participants. One participant demonstrated better maintenance effects associated with SPT-R. Response generalisation to untreated words varied across participants, but was generally modest and unstable. Stimulus generalisation to production of words in sentence completion was positive for three of the participants. Stimulus generalisation to production of phrases was positive for two of the participants. Findings provide additional efficacy data regarding SPT's effects on articulation of treated items and extend knowledge of the treatment's effects when applied to multiple targets within multisyllabic words.

  11. Crystal structure and pharmacological characterization of a novel N-methyl-D-aspartate (NMDA) receptor antagonist at the GluN1 glycine binding site

    DEFF Research Database (Denmark)

    Kvist, Trine; Steffensen, Thomas Bielefeldt; Greenwood, Jeremy R

    2013-01-01

    NMDA receptors are ligand-gated ion channels that mediate excitatory neurotransmission in the brain. They are tetrameric complexes composed of glycine-binding GluN1 and GluN3 subunits together with glutamate-binding GluN2 subunits. Subunit-selective antagonists that discriminate between the glycine...... sites of GluN1 and GluN3 subunits would be valuable pharmacological tools for studies on the function and physiological roles of NMDA receptor subtypes. In a virtual screening for antagonists that exploit differences in the orthosteric binding site of GluN1 and GluN3 subunits, we identified a novel...... displayed >100-fold selectivity for GluN1/N2 NMDA receptors over GluN3A- and GluN3B-containing NMDA receptors and no appreciable effects at AMPA receptors. Binding experiments on rat brain membranes and the purified GluN1 ligand-binding domain using glycine site GluN1 radioligands further confirmed...

  12. Age-dependent neuroprotection of retinal ganglion cells by tempol-C8 acyl ester in a rat NMDA toxicity model.

    Science.gov (United States)

    Fiedorowicz, Michal; Rejdak, Robert; Schuettauf, Frank; Wozniak, Michal; Grieb, Pawel; Thaler, Sebastian

    2014-01-01

    The efficacy of tempol and its acyl derivative tempol-C8 as retinoprotective agents was compared in a rat model of NMDA-induced retinal ganglion cell (RGC) damage. Tempol or tempol-C8 in different doses was administered intraperitoneally to 6 weeks old (pre-adolescent) and 9-10 weeks old (young adult) rats before and after an intravitreous NMDA injection. Retinal ganglion cell were retrogradely labeled with the fluorescent tracer hydroxystilbamidine and RGC counting was performed on retinal flatmounts. Intravitreal NMDA reduced RGC counts by about 90%, independently of age tempol-C8, but not tempol unmodified, showed a significant, dose-dependent RGC rescue effect, with peak activity at 5.8 µmol/kg (p tempol or tempol-C8. In contrast to tempol itself, tempol-C8 acyl ester was neuroprotective in pre-adolescent rats in the NMDA- induced RGC damage model. Therefore, neuroprotection by tempol acyl esters seems to be superior to that of tempol under certain conditions.

  13. Humanin rescues cultured rat cortical neurons from NMDA-induced toxicity through the alleviation of mitochondrial dysfunction

    Directory of Open Access Journals (Sweden)

    Cui A

    2017-04-01

    Full Text Available Ai-Ling Cui,1 Ying-Hua Zhang,2 Jian-Zhong Li,3 Tianbin Song,4 Xue-Min Liu,1 Hui Wang,2 Ce Zhang,5 Guo-Lin Ma,6 Hui Zhang,7 Kefeng Li8 1Anatomy Department, Changzhi Medical College, Changzhi, Shanxi, 2Key Laboratory of Tissue Regeneration of Henan Province, Xinxiang Medical University, Xinxiang, Henan, 3Clinical Laboratory of Heji Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, 4Department of Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 5Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, 6Department of Radiology, China-Japan Friendship Hospital, Beijing, 7Department of Radiology, First Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 8School of Medicine, University of California – San Diego, San Diego, CA, USA Abstract: N-methyl-D-aspartate (NDMA receptor-mediated excitotoxicity has been implicated in a variety of pathological situations such as Alzheimer’s disease (AD and Parkinson’s disease. However, no effective treatments for the same have been developed so far. Humanin (HN is a 24-amino acid peptide originally cloned from the brain of patients with AD and it prevents stress-induced cell death in many cells/tissues. In our previous study, HN was found to effectively rescue rat cortical neurons. It is still not clear whether HN protects the neurons through the attenuation of mitochondrial dysfunction. In this study, excitatory toxicity was induced by NMDA, which binds the NMDA receptor in primarily cultured rat cortical neurons. We found that NMDA (100 µmol/L dramatically induced the decrease of cell viability and caused mitochondrial dysfunction. Pretreatment of the neurons with HN (1 µmol/L led to significant increases of mitochondrial succinate dehydrogenase (SDH activity and membrane potential. In addition, HN pretreatment significantly reduced the excessive production of both reactive oxygen species (ROS and nitric

  14. The neurotoxic effects of amitriptyline are mediated by apoptosis and are effectively blocked by inhibition of caspase activity

    NARCIS (Netherlands)

    Lirk, Philipp; Haller, Ingrid; Hausott, Barbara; Ingorokva, Shota; Deibl, Martina; Gerner, Peter; Klimaschewski, Lars

    2006-01-01

    Oral tricyclic antidepressants, widely used as adjuncts in the treatment of chronic pain, block sodium channels in vitro and nerve conduction in vivo. However, toxicity of amitriptyline has been observed after neural application. We therefore investigated the mechanism and possible prevention of

  15. Effects of ketamine and midazolam on emergence agitation after sevoflurane anaesthesia in children receiving caudal block: a randomized trial

    Directory of Open Access Journals (Sweden)

    Ayse Ozcan

    2014-12-01

    Full Text Available Background and objectives: Emergence agitation is a common postanaesthetic problem in children after sevoflurane anaesthesia. We aimed to compare the effects of ketamine and midazolam administered intravenously, before the end of surgery, for prevention of emergence agitation in children who received caudal block for pain relief under sevoflurane anaesthesia. Methods: 62 American Society of Anesthesiologists patient classification status I children, aged 2–7 years, scheduled for inguinal hernia repair, circumcision or orchidopexy were enrolled to the study. Anaesthesia was induced with sevoflurane 8% in a mixture of 50% oxygen and nitrous oxide. After achieving adequate depth of anaesthesia, a laryngeal mask was placed and then caudal block was performed with 0.75 mL kg−1, 0.25% bupivacaine. At the end of the surgery, ketamine 0.25 mg kg−1, midazolam 0.03 mg kg−1 and saline were given to ketamine, midazolam and control groups, respectively. Agitation was assessed using Paediatric Anaesthesia Emergence Delirium scale and postoperative pain was evaluated with modified Children's Hospital of Eastern Ontario Pain Scale. Results and conclusions: Modified Children's Hospital of Eastern Ontario Pain Scale scores were found higher in control group than in ketamine and midazolam groups. Paediatric Anaesthesia Emergence Delirium scores were similar between groups. Modified Children's Hospital of Eastern Ontario Pain Scale and Paediatric Anaesthesia Emergence Delirium scores showed a significant decrease by time in all groups during follow-up in postanaesthesia care unit. The present study resulted in satisfactory Paediatric Anaesthesia Emergence Delirium scores which are below 10 in all groups. As a conclusion, neither ketamine nor midazolam added to caudal block under sevoflurane anaesthesia did show further effect on emergence agitation. In addition, pain relief still seems to be the major factor in preventing emergence agitation after

  16. Novel NMDA receptor-specific desensitization/inactivation produced by ingestion of the neurotoxins, β-N-methylamino-L-alanine (BMAA) or β-N-oxalylamino-L-alanine (BOAA/β-ODAP).

    Science.gov (United States)

    Koenig, Jane H; Goto, Joy J; Ikeda, Kazuo

    2015-01-01

    The environmental neurotoxins BMAA (β-N-methylamino-L-alanine) and BOAA (β-N-oxalylamino-L-alanine) are implicated as possible causative agents for the neurodegenerative diseases, amyotrophic lateral sclerosis/ParkinsonismDementia complex (ALS/PDC) and neurolathyrism, respectively. Both are structural analogs of the neurotransmitter, glutamate, and bind postsynaptic glutamate receptors. In this study, the effect of ingestion of these toxins on the response of a singly-innervated, identified, glutamatergic postsynaptic cell in a living, undissected Drosophila is observed by intracellular recording. Previously we have reported that ingested BMAA behaves as an NMDA agonist that produces an abnormal NMDA response in the postsynaptic cell. It is shown here that BOAA also behaves as an NMDA agonist, and produces an effect very similar to that of BMAA on the postsynaptic response. In response to a single stimulus, the amplitude of the NMDA component is decreased, while the time to peak and duration of the NMDA component are greatly increased. No discernable effect on the AMPA component of the response was observed. Furthermore, both BMAA and BOAA cause an NMDAR-specific desensitization in response to repetitive stimulation at the physiological frequency for the postsynaptic cell (5 Hz). The possibility that this phenomenon may represent a response to excessive Ca(2+) entry through NMDAR channels is discussed. This desensitization phenomenon, as well as the abnormal NMDAR gating characteristics induced by BMAA, appears to be rescued during higher frequency stimulation (e.g. 10, 20 Hz). Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Firing characteristics of deep dorsal horn neurons after acute spinal transection during administration of agonists for 5-HT1B/1D and NMDA receptors

    Science.gov (United States)

    Thaweerattanasinp, Theeradej; Heckman, Charles J.

    2016-01-01

    Spinal cord injury (SCI) results in a loss of serotonin (5-HT) to the spinal cord and a loss of inhibition to deep dorsal horn (DDH) neurons, which produces an exaggerated excitatory drive to motoneurons. The mechanism of this excitatory drive could involve the DDH neurons triggering long excitatory postsynaptic potentials in motoneurons, which may ultimately drive muscle spasms. Modifying the activity of DDH neurons with drugs such as NMDA or the 5-HT1B/1D receptor agonist zolmitriptan could have a large effect on motoneuron activity and, therefore, on muscle spasms. In this study, we characterize the firing properties of DDH neurons after acute spinal transection in adult mice during administration of zolmitriptan and NMDA, using the in vitro sacral cord preparation and extracellular electrophysiology. DDH neurons can be categorized into three major types with distinct evoked and spontaneous firing characteristics: burst (bursting), simple (single spiking), and tonic (spontaneously tonic firing) neurons. The burst neurons likely contribute to muscle spasm mechanisms because of their bursting behavior. Only the burst neurons show significant changes in their firing characteristics during zolmitriptan and NMDA administration. Zolmitriptan suppresses the burst neurons by reducing their evoked spikes, burst duration, and spontaneous firing rate. Conversely, NMDA facilitates them by enhancing their burst duration and spontaneous firing rate. These results suggest that zolmitriptan may exert its antispastic effect on the burst neurons via activation of 5-HT1B/1D receptors, whereas activation of NMDA receptors may facilitate the burst neurons in contributing to muscle spasm mechanisms following SCI. PMID:27486104

  18. Firing characteristics of deep dorsal horn neurons after acute spinal transection during administration of agonists for 5-HT1B/1D and NMDA receptors.

    Science.gov (United States)

    Thaweerattanasinp, Theeradej; Heckman, Charles J; Tysseling, Vicki M

    2016-10-01

    Spinal cord injury (SCI) results in a loss of serotonin (5-HT) to the spinal cord and a loss of inhibition to deep dorsal horn (DDH) neurons, which produces an exaggerated excitatory drive to motoneurons. The mechanism of this excitatory drive could involve the DDH neurons triggering long excitatory postsynaptic potentials in motoneurons, which may ultimately drive muscle spasms. Modifying the activity of DDH neurons with drugs such as NMDA or the 5-HT 1B/1D receptor agonist zolmitriptan could have a large effect on motoneuron activity and, therefore, on muscle spasms. In this study, we characterize the firing properties of DDH neurons after acute spinal transection in adult mice during administration of zolmitriptan and NMDA, using the in vitro sacral cord preparation and extracellular electrophysiology. DDH neurons can be categorized into three major types with distinct evoked and spontaneous firing characteristics: burst (bursting), simple (single spiking), and tonic (spontaneously tonic firing) neurons. The burst neurons likely contribute to muscle spasm mechanisms because of their bursting behavior. Only the burst neurons show significant changes in their firing characteristics during zolmitriptan and NMDA administration. Zolmitriptan suppresses the burst neurons by reducing their evoked spikes, burst duration, and spontaneous firing rate. Conversely, NMDA facilitates them by enhancing their burst duration and spontaneous firing rate. These results suggest that zolmitriptan may exert its antispastic effect on the burst neurons via activation of 5-HT 1B/1D receptors, whereas activation of NMDA receptors may facilitate the burst neurons in contributing to muscle spasm mechanisms following SCI. Copyright © 2016 the American Physiological Society.

  19. Effect of analgesic nerve block electrical stimulation in a patient with adhesive capsulitis.

    Science.gov (United States)

    Gulick, Dawn T; Borger, Amy; McNamee, Lauren

    2007-01-01

    Although the pathophysiology of adhesive capsulitis is poorly understood, the primary goal of therapeutic intervention is to restore pain-free, functional range of motion (ROM) of the shoulder. Pain and muscle guarding, particularly of the subscapularis muscle, are common impairments that occur with adhesive capsulitis. The purpose of this case report is to describe a novel approach to help the pain-muscle guarding-pain cycle associated with pain and limited shoulder motion in a patient with a medical diagnosis of adhesive capsulitis. The patient was a 64-year-old female with adhesive capsulitis. Outcome variables were the Shoulder Pain and Disability Index (SPADI), internal rotation (IR) and external rotation (ER) ROM, and rotational lack. Twelve treatments of moist heat, analgesic nerve block electrical stimulation, contract/relax exercises for shoulder IR/ER, and Pendulum/Codman exercises were administered. After both 2 and 4 weeks of treatment, the patient demonstrated marked improvements in all areas. Overall, there was a 78-106% increase in ROM (IR and ER) and a 50-83% improvement in functional mobility (rotational lack & SPADI). It appears that analgesic electrical stimulation may have helped decrease the pain-muscle guarding cycle associated with adhesive capsulitis to enhance functional outcomes in a timely manner.

  20. Protective effects of nonionic tri-block copolymers on bile acid-mediated epithelial barrier disruption.

    Energy Technology Data Exchange (ETDEWEB)

    Edelstein, A.; Fink, D.; Musch, M.; Valuckaite, V.; Zabornia, O.; Grubjesic, S.; Firestone, M. A.; Matthews, J. B.; Alverdy, J. C. (Materials Science Division); (Univ. of Chicago)

    2011-11-01

    Translocation of bacteria and other luminal factors from the intestine following surgical injury can be a major driver of critical illness. Bile acids have been shown to play a key role in the loss of intestinal epithelial barrier function during states of host stress. Experiments to study the ability of nonionic block copolymers to abrogate barrier failure in response to bile acid exposure are described. In vitro experiments were performed with the bile salt sodium deoxycholate on Caco-2 enterocyte monolayers using transepithelial electrical resistance to assay barrier function. A bisphenol A coupled triblock polyethylene glycol (PEG), PEG 15-20, was shown to prevent sodium deoxycholate-induced barrier failure. Enzyme-linked immunosorbent assay, lactate dehydrogenase, and caspase 3-based cell death detection assays demonstrated that bile acid-induced apoptosis and necrosis were prevented with PEG 15-20. Immunofluorescence microscopic visualization of the tight junctional protein zonula occludens 1 (ZO-1) demonstrated that PEG 15-20 prevented significant changes in tight junction organization induced by bile acid exposure. Preliminary transepithelial electrical resistance-based studies examining structure-function correlates of polymer protection against bile acid damage were performed with a small library of PEG-based copolymers. Polymer properties associated with optimal protection against bile acid-induced barrier disruption were PEG-based compounds with a molecular weight greater than 10 kd and amphiphilicity. The data demonstrate that PEG-based copolymer architecture is an important determinant that confers protection against bile acid injury of intestinal epithelia.

  1. Radiation chemical effects on polybutadiene polymers, styrene-butadiene block copolymers, and isotactic polypropylene

    International Nuclear Information System (INIS)

    Basheer, R.A.

    1981-01-01

    Electron spin resonance (ESR) of the free radical structure resulting from high energy gamma LNT irradiation of the polymers revealed the presence of allylic free radicals of the type approx. CH.CH = CH.CH 2 approx. The presence of chemically trapped electrons in polybutadiene and styrene-butadiene (SB) block copolymers irradiated in the absence of light at LNT was determined by ESR measurements, and the trapping sites were shown to be impurities or additive molecules which were imbedded in between the polymer chains and which had not been completely removed by purification. Reaction kinetic studies of free radical decay indicated that the decay followed the equation derived for the case in which some free radicals decay by a second order mechanism in the presence of nondecaying free radicals. The same reaction scheme was found to describe the kinetics of alkyl free radical decay in LNT irradiated quenched and annealed isotactic polypropylene with the decay rate of quenched samples being higher than for annealed samples. Results of studies of radiation-induced crosslinking of the elastomers are also included

  2. Effects of a new beta-adrenoceptor blocking agent, S-596 (arotinolol), on isolated dog coronary arteries.

    Science.gov (United States)

    Sakanashi, M; Miyamoto, Y; Takeo, S; Noguchi, K

    1983-06-01

    Effects of S-596 on dog coronary arteries were investigated in vitro. S-596 produced concentration-dependent relaxations of coronary arterial strips under potassium-, prostaglandin (PG) F2 alpha- or PGE2-contracture. S-596-induced relaxations of the strips were not influenced by tetraethylammonium or tranylcypromine, but restored by additional Ca++ or prevented by prior administration of Ca++. In distal portions of coronary arteries, S-596 significantly inhibited concentration-dependent relaxations of the strips induced by norepinephrine and reversed to weak contractions. In proximal portions, S-596 significantly inhibited concentration-dependent contractions induced by norepinephrine. Results indicate that S-596 has a nonspecific relaxant effect on isolated dog coronary arteries maybe through impairment of Ca++ availability and simultaneously has an alpha-adrenoceptor blocking effect, particularly on large coronary arteries.

  3. ASSOCIATIVE EFFECT OF MOLASSES-UREA BLOCK AND FORAGE QUALITY ON NUTRIENT DIGESTION AND NITROGEN RETENTION IN SHEEP

    Directory of Open Access Journals (Sweden)

    lqbal Saeed. M. M. Siddiqui and G. I. Habib

    2002-01-01

    Full Text Available A study was conducted in a 4x4 Latin square design involving four adult crossbred (Kaghani x Rambouillet weather kept in individual metabolic crates and four experimental diets viz: maize stovers (Diet A, maize stovers with 150 g/d molasses-urea block (Diet B, lucerne hay (Diet Cand lucerne hay with 150 g/d molasses-urea block (Diet D. The forage intake was restricted to 2% of body weight. Each experimental period consisted 10 days of adaptation followed by five days of data collection. Total dry matter intake on molasses-urea block (MUB supplemented diets was higher (p<0.05 than unsupplemented diets. The daily quantity of total dry matter and water consumed by weathers was higher (p < 0.001 on MUB supplemented diets. Water consumption was positively co-related to nitrogen intake (r2 0.66: p< 0.00 I and varied due to diets (p < 0.00 I. in vivo dry matter digestibility (DMD and organic matter digestibility (OMD of lucerne hay-based diets were greater (P< 005 than those containing maize stovers. Supplementation of MUB did not affect the DMD or OMD of the diets. The interaction of MUB and forage (P = 0.06 revealed that MUB was effective in increasing (P< 0.05 the nitrogen digestibility of maize stovers from 30,59% on diet A to 51.33% on diet B but did not affect the nitrogen digestibility in animals fed lucerne hay. The wethers receiving lucerne hay-based diets retained more nitrogen (p< 0.001 than those given maize stovers (8.50 's 3,12 g/d. Molasses-urea block supplementation on both forages increased (p < 0.05 the nitrogen retention. Mean nitrogen retention was I 82. 4.41, 7 .19 and 9.82 gld in wethers receiving diets A. B. C and D. respectively. Mean rumen ammonia concentration (mg N/lOO ml in wethers receiving maize stovers. was 10.52. which increased (p< 0,05 to 17.87 in response to MUB supplementation. On lucerne hay. the rumen ammonia concentrations did not change due to MUB and the mean values on diets C and D were 24,24 and 29.88 mg N/100

  4. Fluctuations, Finite-Size Effects and the Thermodynamic Limit in Computer Simulations: Revisiting the Spatial Block Analysis Method

    Directory of Open Access Journals (Sweden)

    Maziar Heidari

    2018-03-01

    Full Text Available The spatial block analysis (SBA method has been introduced to efficiently extrapolate thermodynamic quantities from finite-size computer simulations of a large variety of physical systems. In the particular case of simple liquids and liquid mixtures, by subdividing the simulation box into blocks of increasing size and calculating volume-dependent fluctuations of the number of particles, it is possible to extrapolate the bulk isothermal compressibility and Kirkwood–Buff integrals in the thermodynamic limit. Only by explicitly including finite-size effects, ubiquitous in computer simulations, into the SBA method, the extrapolation to the thermodynamic limit can be achieved. In this review, we discuss two of these finite-size effects in the context of the SBA method due to (i the statistical ensemble and (ii the finite integration domains used in computer simulations. To illustrate the method, we consider prototypical liquids and liquid mixtures described by truncated and shifted Lennard–Jones (TSLJ potentials. Furthermore, we show some of the most recent developments of the SBA method, in particular its use to calculate chemical potentials of liquids in a wide range of density/concentration conditions.

  5. The effect of different component ratios in block polymers and processing conditions on electrodeposition efficiency onto titanium

    Science.gov (United States)

    Fukuhara, Yusuke; Kyuzo, Megumi; Tsutsumi, Yusuke; Nagai, Akiko; Chen, Peng; Hanawa, Takao

    2015-11-01

    2-Methacryloyloxyethyl phosphorylcholine (MPC) polymers for electrodeposition to titanium surfaces were synthesized. The polymers were block-type copolymers composed of a poly(MPC) segment and a poly(2-aminoethylmethacrylate (AEMA)) segment, which could electronically adsorb to a titanium oxide film on the titanium surface. The polymer was synthesized as expected by nuclear magnetic resonance and gel permeation chromatography. In a 0.26 mmol L-1 PMbA solution adjusted to pH 11, -3.0 V (vs. an Ag/AgCl electrode) was applied to a titanium substrate for 300 s. We evaluated the effects of the molecular structure of poly(MPC-block-AEMA) (PMbA) with a different polymerization degree of MPC unit, whereas the polymerization degree of the AEMA units w