9 research outputs found
Quinolinate and related excitotoxins: mechanisms of neurotoxicity and disease relevance
No full textThere are many ways in which neuronal damage can be produced in the brain, including the overactivation of depolarizing receptors, exposure to high levels of pro-inflammatory proteins such as cytokines, or miscellaneous toxins, but the kynurenine pathway has emerged as a novel but potentially major factor in regulating neuronal viability or death. It is the major route for the metabolism of the essential amino acid tryptophan, which is oxidized by indoleamine-2,3-dioxygenase (IDO) to a series of compounds which can activate, block, or modulate conventional neurotransmitter receptors. Quinolinic acid is an agonist at N-methyl-d-aspartate receptors, kynurenic acid is an antagonist at these and other glutamate receptors, and other kynurenine metabolites are highly redox-active. Superimposed on the discovery of this neuromodulatory pathway have been observations that activity in the pathway is linked to neurological and psychiatric disorders, correlating with disease state (as in Huntington’s disease) or cognitive function (as following bypass surgery). Together, the data accumulated to date make a strong case for this hitherto obscure pathway being a major factor in determining cell damage, death, or recovery in health and disease
The relationship between the monitored performance of tutors and students at PBL tutorials and the marked hypotheses generated by students in a hybrid curriculum
No full textIntroduction: There have been a number of published studies examining the link between the effectiveness of the problem-based learning (PBL) process and students’ performance in examinations. In a hybrid PBL/lectures curriculum, the results of such studies are of limited use because of the difficulty in dissociating the knowledge gained at lectures from that gained through PBL-related activities. Hence, the objectives of this study were: (1) to develop an instrument to measure the performance of tutors and students at PBL tutorials, and (2) to explore the contribution of such performances to the marks attained by students from the hypotheses generated at PBL tutorials. Methods: A monitoring instrument for assessing the performances of non-expert tutors and students at tutorials was developed and validated using principal component analysis and reliability analysis. Also, a rubric was formulated to enable a content expert to assign marks to the quality of hypotheses generated. Results: The monitoring instrument was found to be valid and reliable. There was a significant correlation between the performance of tutors at tutorials and hypotheses marks. In contrast, there was no significant correlation between the performance of students and hypotheses marks. Discussion: The monitoring instrument is a useful tool for improving the PBL process, especially where the medical programme depends on non-expert PBL tutors. In addition to ensuring good PBL processes, it is important that students achieve the desired output at PBL tutorials by producing hypotheses that help them understand the basic sciences underlying the clinical cases. The latter is achieved by the use of an open-ended rubric by a subject expert to assign marks to the hypotheses, a method that also provides additional motivation to students to develop relevant and detailed hypotheses
Quinolinic Acid and Related Excitotoxins: Mechanisms of Neurotoxicity and Disease Relevance
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 – a putative GABA-releasing agent – on rat hippocampal slices and neocortical activity in vivo
No full textEffects of Jasminum multiflorum leaf extract on rodent models of epilepsy, motor coordination and anxiety
No full textThe 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
