17 research outputs found
Effects of ethylenediamine – a putative GABA-releasing agent – on rat hippocampal slices and neocortical activity in vivo
No full textThe simple diamine diaminoethane (ethylenediamine, EDA) has been shown to activate GABA receptors in the central and peripheral nervous systems, partly by a direct action and partly by releasing endogenous GABA. These effects have been shown to be produced by the complexation of EDA with bicarbonate to form a carbamate. The present work has compared EDA, GABA and [beta]-alanine responses in rat CA1 neurons using extracellular and intracellular recordings, as well as neocortical evoked potentials in vivo. Superfusion of GABA onto hippocampal slices produced depolarisation and a decrease of field epsps, both effects fading rapidly, but showing sensitivity to blockade by bicuculline. EDA produced an initial hyperpolarisation and increase of extracellular field epsp size with no fade and only partial sensitivity to bicuculline, with subsequent depolarisation, while [beta]-alanine produces a much larger underlying hyperpolarisation and increase in fepsps, followed by depolarisation and inhibition of fepsps. The responses to [beta]-alanine, but not GABA or EDA, were blocked by strychnine. In vivo experiments, recording somatosensory evoked potentials, confirmed that EDA produced an initial increase followed by depression, and that this effect was not fully blocked by bicuculline. Overall the results indicate that EDA has actions in addition to the activation of GABA receptors. These actions are not attributable to activation of [beta]-alanine-sensitive glycine receptors, but may involve the activation of sites sensitive to adipic acid, which is structurally equivalent to the dicarbamate of EDA. The results emphasise the complex pharmacology of simple amines in bicarbonate-containing solution
The serine protease subtilisin suppresses epileptiform activity in rat hippocampal slices and neocortex in vivo
No full textSerine proteases of the S8A family and those belonging to the subtilase group generate a long-lasting inhibition of hippocampal evoked potentials, which shows little recovery and resembles long-term depression. The present work investigates the effects of subtilisin A on epileptiform activity induced in hippocampal slices. Interictal bursts were generated by perfusion with 4-aminopyridine in magnesium-free medium, whereas ictal bursts were produced by the addition of baclofen. Subtilisin A superfused for 10 min at concentrations of 50 nM and above reduced the duration of ictal bursts, whereas higher concentrations reduced the frequency of interictal activity with little or no recovery, indicating similarity with the long-term depression reported previously. The anti-epileptiform activity was not prevented by inhibitors of phosphatases or several kinases, but the inhibition of ictal activity was selectively reduced by the tyrosine kinase inhibitor genistein. The rho-activated coiled-coil kinase (ROCK) inhibitor Y-27632 had no effect on the suppression of ictal or interictal bursts. Subtilisin applied at nanomolar concentrations to the surface of the cerebral cortex in vivo also suppressed epileptiform spikes induced by bicuculline. It is concluded that serine proteases of the subtilase group are highly potent inhibitors of epileptiform activity, especially ictal bursts, and that tyrosine kinases may be involved in that inhibition. The mechanism of inhibition is different from the long-lasting depression of evoked potentials, which is partly mediated via ROCK
Interactions of glutamate receptor agonists with long-term potentiation in the rat hippocampal slice
No full textEffects of AMPA and clomethiazole on spreading depression cycles in the rat neocortex in vivo
No full textIn hippocampal slices, inhibition of AMPA receptors unmasks synaptic transmission via NMDA receptors, suggesting that AMPA receptor activation normally inhibits synaptic transmission via NMDA receptors. Activation of NMDA receptors is involved in the pathogenesis of cortical spreading depression (CSD) which has been implicated in the pathogenesis of migraine aura and neuronal damage from pen-infarct depolarizations. In this study we examined whether NMDA receptor transmission could be unmasked in the neocortex in vivo by AMPA receptor blockage and whether AMPA receptors could affect CSD induced by 200 mM KCl. We further compared the effects of AMPA to those of the NMDA receptor antagonist, 2-amino-5-phosphono-pentanoic acid (2AP5), and the GABA-mimetic drug clomethiazole. The NMDA receptor antagonist MK-801 did not affect the baseline somatosensory evoked potentials (SEPs). In a medium with no Mg2+, the AMPA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) caused marked reduction in the SEP size which subsequently recovered partially; MK-801 blocked these partially recovered SEPs. AMPA (50 mu M but not at 5 mu M or 250 mu M) and 2AP5 (10 mu M) significantly reduced the number of CSD cycles. The effect of AMPA was not changed by co-applying it with cyclothiazide, which blocks AMPA receptor desensitization. Clomethiazole (100 mg/kg i.p.) did not significantly affect the number of CSD cycles. Only 2AP5 significantly reduced the potentiation that follows CSD. We conclude that activation of AMPA receptors can suppress the actions of NMDA receptors in the neocortex; this could be an intrinsic protective mechanism against CSD and also provide a possible therapeutic strategy against CSD-related neurological conditions. (C) 2010 Elsevier B.V. All rights reserve
Effects of ethylenediamine in rodent models of seizure, motor coordination and anxiety
No full textEthylenediamine (EDA) activates GABAA receptors via both direct and indirect mechanisms. EDA has been shown to reduce seizures caused by systemic injection of proconvulsants in an animal model of generalized tonic–clonic seizures. However, there does not appear to have been any report on the effects of EDA in other seizure models. Hence, we used male Sprague-Dawley rats to test the effects of EDA on topically applied bicuculline (a model of simple partial seizures) and on maximal electroshock (MES, a model of generalized tonic–clonic seizures). We also examined the effects of EDA on motor coordination using a rotarod treadmill, and its potential anxiolytic properties using an elevated plus maze (EPM). EDA at concentrations of 50 μM and above reduced the frequency of epileptiform spikes on an electrocorticogram in a concentration-dependent manner. EDA at 100 and 1000 mg/kg i.p. increased the threshold for inducing limb extension on the MES. EDA did not affect the time spent by rats on the rotarod at 10 or 100 mg/kg, but significantly reduced the time spent at doses of 1000 mg/kg. In the EPM, EDA at 10 or 100 mg/kg significantly increased the frequency of entries and time spent in the open arms. We conclude that EDA has antiepileptic and anxiolytic activity at doses that do not affect motor coordination
The reactor physics of the Massachusetts Institute of Technology reactor redesign
No full text"August, 1970."Also written as a Ph. D. thesis by the first author and supervised by the second and third author, MIT, Dept. of Nuclear Engineering, 1970Includes bibliographical references (pages 284-289)An H20 cooled compact MITR-II core, reflected by D20 has been designed for the MITR to increase the reflector thermal neutron flux at tips of beam ports by a factor of 3 or better, without changing the operating power level of the reactor. The diffusion approximation to the neutron transport equation has been used. A three neutron energy group scheme, that retains essential spatial effects, used in the studies has yielded satisfactory agreement with measured data. The factors which affect the intensity as well as the quality of the reflector thermal neutron flux have been studied. These studies show that the permanent features of the MITR limit the maximum power densities in the MITR-II core to factors between 4.5 and 12 below the corresponding values in reactors employing a similar core concept Nevertheless, the predicted unperturbed reflector thermal neutron flux of 1.lXlO14 n/cm 2-sec in MITR-II yields a reflector flux per unit power that is competitive with the corresponding values available in reactors of its type and a factor of 5.0 higher than that in MITR-I
Molecular changes associated with hippocampal long-lasting depression induced by the serine protease subtilisin-A
No full textThe serine protease subtilisin-A (SubA) induces a form of long-term depression (LTD) of synaptic transmission in the rat hippocampus, and molecular changes associated with SubA-induced LTD (SubA-LTD) were explored by using recordings of evoked postsynaptic potentials and immunoblotting. SubA-LTD was prevented by a selective inhibitor of SubA proteolysis, but the same inhibitor did not affect LTD induced by electrical stimulation or activation of metabotropic glutamate receptors. SubA-LTD was reduced by the protein kinase inhibitors genistein and lavendustin A, although not by inhibitors of p38 mitogen-activated protein kinase, glycogen synthase kinase-3, or protein phosphatases. It was also reduced by (<i>RS</i>)-α-methyl-4-carboxyphenylglycine, a broad-spectrum antagonist at metabotropic glutamate receptors. Inhibition of the Rho kinase enzyme Rho-associated coiled-coil kinase reduced SubA-LTD, although inhibitors of the RhoGTPase-activating enzymes farnesyl transferase and geranylgeranyl transferase did not. In addition, a late phase of SubA-LTD was dependent on new protein synthesis. There was a small, non-significant difference in SubA-LTD between wild-type and RhoB<sup>-/-</sup> mice. Marked decreases were seen in the levels of Unc-5H3, a protein that is intimately involved in the development and plasticity of glutamatergic synapses. Smaller changes were noted, at higher concentrations of SubA, in Unc-5H1, vesicle-associated membrane protein-1 (synaptobrevin), and actin, with no changes in the levels of synaptophysin, synaptotagmin, RhoA, or RhoB. None of these changes was associated with LTD induced electrically or by the metabotropic glutamate receptor agonist (<i>RS</i>)-3,5-dihydroxyphenylglycine. These results indicate that SubA induces molecular changes that overlap with other forms of LTD, but that the overall molecular profile of SubA-LTD is quite differen
High-risk fertility behaviours among women in sub-Saharan Africa
No full textSeidu A-A, Ahinkorah BO, Anjorin SS, et al. High-risk fertility behaviours among women in sub-Saharan Africa. Journal of Public Health. 2021:1-11.BACKGROUND: High-risk fertility behaviours such as too early or advanced age at delivery, shorter birth interval, birth order and a higher number of live births to a woman often lead to adverse maternal and child health outcomes. We assessed high-risk fertility behaviours and their associated factors among women in sub-Saharan Africa (SSA).; METHODS: Data on 200716 women pooled from the demographic and health surveys of 27 countries conducted between 2010 and 2020 in SSA were analysed. High-risk fertility behaviour from four indicators, mother aged 34 years at the time of delivery; mother of a child born after a short birth interval (3 children), was derived. Multi-level multi-variable logistic regression analyses were carried out and the results were presented as adjusted odds ratios at 95% confidence interval.; RESULTS: Women who were in polygamous marriages had higher odds of single and multiple high-risk fertility behaviour compared with their counterparts who were in monogamous marriages. Women with middle or high maternal decision-making power had higher odds of single and multiple high-risk fertility behaviours compared with those with low decision-making power. Single and multiple high-risk fertility behaviours were lower among women with access to family planning, those with at least primary education and those whose partners had at least primary education compared with their counterparts who had no access to family planning, those with no formal education and those whose partners had no formal education.; CONCLUSION: Family structure, women's decision-making power, access to family planning, women's level of education and partners' level of education were identified as predictors of high-risk fertility behaviours in SSA. These findings are crucial in addressing maternal health and fertility challenges. Policy makers, maternal health and fertility stakeholders in countries with high prevalence of high parity and short birth intervals should organize programs that will help to reduce the prevalence of these high-risk factors, taking into consideration the factors that predispose women to high-risk fertility behaviours. © The Author(s) 2021. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: [email protected]
Estudo fitoquímico, toxicológico e dos efeitos neuroprotetor e tipo antidepressivo do extrato aquoso de Aloysia gratissima (Gill et Hook) Troncoso (erva santa)
No full textTese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Programa de Pós-Graduação em Neurociências, Florianópolis, 2011Aloysia gratissima é uma planta utilizada para tratar sintomas de doenças relacionadas principalmente aos sistemas respiratório e, nervoso central, no Brasil, Argentina, Paraguai e Uruguai. Seu uso popular não vem sendo acompanhado por estudos científicos que poderiam garantir um uso com qualidade, eficácia e segurança. Neste estudo foi investigado o perfil sazonal metabólico do extrato aquoso de Aloysia gratissima (EA) e identificados e quantificados compostos fenólicos (ácido ferúlico, trans-cinâmico e ácido p-cumárico) e carotenoídicos (luteína e trans-ß-caroteno) majoritários, conhecidos pela capacidade antioxidante. A avaliação de toxicidade aguda revelou um uso seguro de EA abaixo de 2000 mg/kg em camundongos. Foram evidenciados os efeitos: antioxidante, neuroprotetor frente à excitotoxicidade glutamatérgica e tipo antidepressivo. Os estudos dos mecanismos envolvidos no efeito neuroprotetor do EA demonstraram o envolvimento de modulação do transporte de glutamato, ativação da via PI3K, diminuição da expressão de iNOS e antagonismo ao receptor NMDA. EA não preveniu o surgimento de convulsões induzidas pelo ácido quinolínico, no entanto foi evidenciado um efeito neuroprotetor através da modulação do transporte de glutamato. A participação do receptor NMDA, da via L-arginina-NO-cGMP e do sistema monoaminérgico foram evidenciados no efeito tipo antidepressivo do EA. O composto majoritário do EA, ácido ferúlico, exerceu um efeito tipo antidepressivo em camundongos, sugerindo a participação do sistema serotoninérgico neste efeito. Desta forma, o EA e o ácido ferúlico demonstraram seu potencial na prevenção ou tratamento de doenças que envolvem os sistemas, serotoninérgico e glutamatérgico.Aloysia gratissima is a plant used to treat symptoms mainly related to the respiratory and central nervous systems in Brazil, Argentina, Paraguay, and Uruguay. It.s popular use has not been accompanied by scientific studies that could provide a contribution to quality, efficacy, and safety. Our study showed a seasonal metabolic profile of Aloysia gratissima.s aqueous extract (AE), which major phenolic (ferulic acid, trans-cinnamic, and p-coumaric acid) and carotenoid (lutein and trans-ß-carotene) compounds were identified and quantified. These compounds are known for their antioxidant capacity. Acute toxicity evaluation of AE in mice demonstrated to be safe in doses below 2000 mg/kg. Our data suggest that AE exerts biological effects such as antioxidant, neuroprotective against the glutamatergic excitotoxicity and antidepressant-like activity. The neuroprotective effect of AE against glutamatergic excitotoxicity involved glutamate transport modulation, PI3K pathway activation, decreasing iNOS expression and possible NMDA receptor antagonism. Although AE did not protect animals against quinolinic acid-induced seizures, it showed neuroprotective effect by glutamate transport modulation. The involvement of NMDA receptor, L-arginine-NO-cGMP pathway, and monoaminergic system were evidenced in the antidepressant-like effect of AE. The major component of AE, ferulic acid, was also able to exert antidepressant-like effect in mice. Serotonergic system participation and a synergistic activity with conventional antidepressants were demonstrated in this effect. Thus, AE and ferulic acid showed their potential use in preventing or treating diseases that involves glutamatergic and serotoninergic systems
