Effects of Jasminum multiflorum leaf extract on rodent models of epilepsy, motor coordination and anxiety.

Jasmine flowers and leaves are used extensively in folk medicine in different parts of the world to treat a variety of diseases. However, there are very few published reports on the neuropsychiatric effects of Jasmine extracts. Hence, the objectives of the present study were to examine the effects of an alcohol extract of Jasminum multiflorum leaves on topically-applied bicuculline (a model of acute simple partial epilepsy) and maximal electroshock (MES, a model of generalized tonic-clonic seizure) in male Sprague-Dawley rats. The objectives also included an examination of the anxiolytic properties of the extract using an elevated plus maze and the effect of the extract on motor coordination using a rotarod treadmill. Phytochemical analysis of the extract showed the presence of three flavonoids and four additional compounds belonging to the steroid, terpenoid, phenol or sugar classes of compounds. The Jasmine alcohol extract, diluted with water and given orally or intraperitoneally, reduced the number of bicuculline-induced epileptiform discharges in a dose-dependent manner. The extract did not cause a significant increase in the current needed to induce hind limb extension in MES experiments. The extract significantly affected motor coordination when injected at 500mg/kg but not at 200mg/kg. At the latter dose, the extract increased open-arm entries and duration in the elevated plus maze to a level comparable to that of diazepam at 2mg/kg. We conclude that Jasmine leaf extract has a beneficial effect against an animal model of acute partial complex epilepsy, and significant anxiolytic effect at a dose that does not affect motor co-ordination.

The relationship between the monitored performance of tutors and students at PBL tutorials and the marked hypotheses generated by students in a hybrid curriculum.

INTRODUCTION: 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.

Effects of ethylenediamine in rodent models of seizure, motor coordination and anxiety.

Ethylenediamine (EDA) activates GABA(A) 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 100mg/kg, but significantly reduced the time spent at doses of 1000 mg/kg. In the EPM, EDA at 10 or 100mg/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.

Molecular changes associated with hippocampal long-lasting depression induced by the serine protease subtilisin-A.

The 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 (RS)-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(-/-) 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 (RS)-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 different.

Effects of ethylenediamine--a putative GABA-releasing agent--on rat hippocampal slices and neocortical activity in vivo

The 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 β-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 β-alanine produces a much larger underlying hyperpolarisation and increase in fepsps, followed by depolarisation and inhibition of fepsps. The responses to β-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 β-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 solutions.

Effects of ethylenediamine--a putative GABA-releasing agent--on rat hippocampal slices and neocortical activity in vivo.

The 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 ß-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 ß-alanine produces a much larger underlying hyperpolarisation and increase in fepsps, followed by depolarisation and inhibition of fepsps. The responses to ß-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 ß-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 solutions.

Effects of AMPA and clomethiazole on spreading depression cycles in the rat neocortex in vivo.

In 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 peri-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 Mg(2+), 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 µM but not at 5 µM or 250 µM) and 2AP5 (10 µM) 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.

AMPA receptor activation reduces epileptiform activity in the rat neocortex.

We have previously reported that topical application of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) to the rat neocortex prevents the effects of a subsequent application of N-methyl-d-aspartic acid (NMDA). Activation of NMDA receptors is involved in the pathogenesis of epileptic activity. Therefore, we examined if topically applied AMPA could affect changes in the somatosensory evoked potentials (SEPs) and electrocorticogram (ECoG) epileptic spikes caused by bicuculline. AMPA (50 microM) prevented the epileptiform activity to a level that was comparable to that caused by diazepam (3 mg/kg i.p.) or clomethiazole (100 mg/kg i.p.). Also, the epileptiform activity was suppressed by the AMPAR antagonist, CNQX, or the blocker of AMPAR desensitization, cyclothiazide. In the hippocampal slice, bicuculline-induced changes in the population spike potentials recorded from the CA1 cells were not affected by AMPA. We conclude that in the complex neuronal network of the rat neocortex, epileptiform activity can be suppressed in a variety of strategies that target the AMPA receptors: (1) blocking AMPA receptors, (2) promoting an apparent desensitization of AMPA receptors (possibly on the pyramidal neurons) or (3) reducing an apparent desensitization of AMPA receptors (possibly on the inhibitory GABA-ergic interneurons).

NMDA-induced preconditioning attenuates synaptic plasticity in the rat hippocampus.

It was recently demonstrated that glutamate could precondition hippocampal slices against the damaging effects of hypoxia, and we have now extended this observation by investigating (i) the ability of glutamate receptor agonists to act as preconditioning agents and (ii) the effects of preconditioning on synaptic plasticity. Using rat hippocampal slices, 15 microM NMDA applied for 10 min (chemical insult) caused abolition of the population spike potentials (PS) followed by approximately 33% recovery at 60 min post-insult. In comparison, a 5 min preconditioning exposure of 10 microM NMDA given 30 min prior to the insult significantly improved the recovery to 69%. Preconditioning did not alter paired pulse facilitation; however, it significantly enhanced paired pulse depression and reduced population spike long-term potentiation (PS-LTP) and LTP in field recordings. This effect on PS-LTP appeared to be NMDA receptor dependent and was blocked by the nitric oxide synthase inhibitors nitro-L-arginine methyl ester (L-NAME) and 7-nitro indazole (7-NI) but not by the adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). We conclude that preconditioning by NMDA can improve recovery following acute insults but may have deleterious effects on neuronal plasticity.

LTP-induced depression of response to hypoxia in hippocampus: effects of adenosine receptor activation.

Previous work has shown that long-term potentiation (LTP) can reduce the effects of hypoxia in depressing population spikes in rat hippocampal slices. We have now investigated the role of adenosine in this phenomenon. There is no mutual inhibition between the depressant effects of hypoxia and adenosine, but LTP reduces responses to both hypoxia and adenosine, as does application of an A1 receptor antagonist. The effect of LTP is not due to a change in the balance of activation of A1 and A2A adenosine receptors since a selective A2A receptor antagonist did not prevent the interaction. We suggest that LTP may reduce the response to hypoxia by attenuating neuronal sensitivity to adenosine A1 receptors.

Neuroprotective role of learning in dementia: a biological explanation.

Several epidemiological studies have found an association between low educational level (or low cognitively demanding occupations) and dementia. Although other studies have not found evidence to support such an association, there has been a general trend toward a "use it or lose it" concept which attempts to promote a neuroprotective role of intellectual activity against the development of dementia. Formation of amyloid-beta peptide (Abeta) in the brain plays a key role in the development of Alzheimer's disease whilst glutamate has been implicated in the pathophysiology of a number of neurological disorders including Alzheimer's disease and vascular dementia. Abeta can mediate neurodegeneration by a complex interaction of neurodegenerative processes that involve increasing extracellular concentration of glutamate, increasing intracellular Ca2+ concentration, and apoptosis. Long-term potentiation (LTP, a biological correlate of learning and memory) increases the sensitivity of hippocampal neurons to synaptically released glutamate whilst decreasing responses of neurons to bath applied glutamate receptor agonists and to hypoxia/ischemia in vitro. The effects of LTP are likely to involve changes in intracellular Ca2+ concentration. Based on these findings we are proposing that the LTP-induced neuroprotection in vitro may help explain the epidemiological evidence of a possible neuroprotective role of high intellectual activity against dementia.

The pharmacological manipulation of glutamate receptors and neuroprotection.

The overactivation of glutamate receptors is a major cause of Ca(2+) overload in cells, potentially leading to cell damage and death. There is an abundance of agents and mechanisms by which glutamate receptor activation can be prevented or modulated in order to control these effects. They include the well-established, competitive and non-competitive antagonists at the N-methyl-D-aspartate (NMDA) receptors and modulators of desensitisation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors. More recently, it has emerged that some compounds can act selectively at different subunits of glutamate receptors, allowing a differential blockade of subtypes. It is also becoming clear that a number of endogenous compounds, including purines, can modify glutamate receptor sensitivity. The kynurenine pathway is an alternative but distinct pathway to the generation of glutamate receptor ligands. The products of tryptophan metabolism via the kynurenine pathway include both quinolinic acid, a selective agonist at NMDA receptors, and kynurenic acid, an antagonist at several glutamate receptor subtypes. The levels of these metabolites change as a result of the activation of inflammatory processes and immune-competent cells, and may have a significant impact on Ca(2+) fluxes and neuronal damage. Drugs which target some of these various sites and processes, or which change the balance between the excitotoxin quinolinic acid and the neuroprotective kynurenic acid, could also have potential as neuroprotective drugs.

The pharmacological manipulation of glutamate receptors and neuroprotection

The overactivation of glutamate receptors is a major cause of Ca2+ overload in cells, potentially leading to cell damage and death. There is an abundance of agents and mechanisms by which glutamate receptor activation can be prevented or modulated in order to control these effects. They include the well-established, competitive and non-competitive antagonists at the N-methyl-D-aspartate (NMDA) receptors and modulators of desensitisation of the  -amino-3-hydroxy-5-mmethyl-4-isoxazole-propionic acid (AMP) receptors. More recently, it has emerged that some compounds can acrt selectively at different subnuits of glutamate receptors,allowing a different blockade of subtypes. It is also becoming clear that a number of endogenous compounds, including purines, can modify glutamate receptor senistivity. The kynurenine pathway is an alternative but distinct pathway to the generation glutamate receptor ligands. The products of tryptophan metablism via kynurenine pathway include both quinolinic acid, a selective agonist at several glutamate receptor subtypes. The levels of these metabolites change as a result of the activation of inflammatory processes and immune-competent cells, and may have a significant impact on Ca2+ fluxes and neuronal damage. Drugs which target some of these various sites and processes, or which change the balance between the excitotoxin quinolinic acid and the neuroprotective kynurenic acid, could also have potential as neuroprotective drugs (AU)

Quantification of microvascular resistance in patients with diabetes mellitus [abstract]

Near Infrared Photoplethysmography (NIRP) is a non-invasive technique that has the potential to be used to assess the state of the peripheral nerves and microcirculation. However, the parameters that reflect the state of the microvascular system have not been established. Therefore, we tested the hypothesis that the resistance of the blood vessels in the microcirculation can be determined by analyzing the temporal components of the photoplethysmographic trace. NIRP incorporates two light-emitting diodes and a photodetector. The emergent light enters the skin and penetrates to the level of the dermis, is backscattered, collected by the photodetector and converted to a recordable trace. This trace consists of a series of pulses synchronous with the heart period, Th. It is possible to divide each pulse into a rise time from baseline to peak, Tg, and fall time from peak to baseline, Ta. All NIRP recordings were taken from the right index finger with the person in the supine position. In a first study involving five healthy male volunteers, the subjects right arm was cuffed approximately three minutes during which he exercised the fingers to increase a buildup of tissue metabolites; this was done in order to decrease microvascular resistance. In a second study, the above parameters (Th, Tg and Ta) were measured in 31 patients with chronic diabetes mellitus (diabetic group, DG) and compared to those of 29 healthy normal persons (healthy group, HG). In the first study, the ratio of the rise time to the heart period (Tg/Th) or of the rise time of the fall time (Tg/Ta) was increased, whereas that to the fall time of the heart period (Ta/Th) was decreased. In the second study, the mean for the Tg/Th was 0.235 ñ 0.008 (mean ñ sem) for the HG and 0.292 ñ 0.007 for the DG; the increase was highly significant, p< 0.001 (one-tail unpaired t-test). The mean for the Tg/Ta was 0.312 ñ 0.013 for the HG and 0.413 ñ 0.012 for the DG; this increase was also highly significant, p< 0.001. The mean for the Ta/Th was 0.765 ñ 0.008 for the HG and 0.711 ñ 0.006 for the DG; the decrease was highly significant, p< 0.001. In conclusion, an increase in microvascular resistance was reflected in an increase in the rise time and a decrease in the fall time. Thus this system appears to be a useful one in quantifying the increase in microvascvular resistance in diabetics. (AU)

Plasma concentrations of vitamins A and E in healthy and diabetic individuals [abstract]

Type 2 diabetes mellitus is highly prevalent in Trinidad and Tobago and is associated with severe morbidity. It is possible that poor antioxidant status, such as low levels of plasma vitamin E and A, may increase the clinical complications of diabetes mellitus. The present study assessed the adequacy of antioxidant protection in Type 2 diabetics by quantitating plasma levels of vitamins A and E. Blood was taken in EDTA tubes from 11 diabetic patients and from 9 healthy individuals, who served as controls. Plasma obtained was stored in Butylated hydroxy toluene at -70§C until susequently assayed for the antioxidants vitamins A and E, using a reverse-phase high pressure liquid chromoatography. Additionally, in the diabetics HbA1c levels were measured by immunoassay, using the DCA 2000 Analyser (Bayer Corporation, USA). In the diabetics HbA1c values ranged from 4.3 percent to 11.3 percent with the mean ñ SEM being 7.79 ñ 0.81 percent. The mean ñ SEM vitamin E concentration in the diabetics was 26.32 ñ 3.14 umol/L; this was not significantly different from the controls (27.39 ñ 1.66 umol/L). Plasma vitamin A in the diabetic group (1.99 ñ 0.19 æmol/L), was significantly higher (p< 0.001) than in controls (1.14 ñ 0.12 æmol/L). The interassay coefficient of variation for the high pressure liquid chromatography method was 4.3 percent and 1.15 percent for vitamins A and E, respectively. In the diabetic group there was a good relationship between vitamin A and HbA1c (r= -o.522; p= 0.099); however, this was not significant. Similarly, the relationship between vitamin A and HbA1c (r= 0.230; n= 11) was not significant. In conclusion, it was found that glycaemic control as measured by HbA1c varied amongst diabetics. The difference in vitamin E status between diabetics and non-diabetics was not significant. However, vitamin A levels for non-diabetics were significantly lower than for diabetes. (AU)

A molecular form of memory protects the brain from the effects of acute hypoxia [abstract]

Long-term potentiation (LTP) is a molecular engram of memory. Previous work has demonstrated that LTP decreases the sensitivity of glutamate receptors in the rat hippocampus. Glutamate has beem implicated in the pathogenesis of hypoxic/ischaemic damage. We therefore tested the hypothesis that LTP could reduce the effects of LTP on hypoxia in the rat hippocampus. The effects of LTP on hypoxia were measured by the changes in the extracellular potentials recorded from the hippocampal slice. Hypoxia was induced by perfusing the slice with artificial cerebrospinal fluid that contained varying concentrations of oxygen. Each slice was initially exposed to the hypoxic medium for 1.5-3.0 minutes. This led to a decrease in the potentials, which recovered to control levels within 5 minutes. Repeat exposure to the same hypoxic medium for the same duration as the first, also caused a reduction in the potentials. There was no significant difference between the degree of reduction caused by the first or second exposure for all types of hypoxic media tested (p >0.05; paired t test). In some slices, LTP was induced after the first hypoxic exposure. LTP brought about an inhibition of the reduction in potentials caused by the second hypoxic insult; the differences in reducation in potentials were highly significant for all the hypoxic media used (p <0.01; paired t test). The neuroprotective effects of LTP were not prevented by cyclothiazide (an inhibitor of AMPA receptor desensitization) or NOS inhibitors (antagonists of intracellular nitric oxide production). These compounds have been shown to be effective in blocking the effects of LTP on the actions of exogenously applied AMPA and NMDA, respectively. The neuroprotective effects of LTP were similar to that of propentofylline, a known neuroprotective compound. We conclude that LTP causes an appreciable protection of the hippocampus slices to in-vitro models of acute hypoxia. There have been reports that there is a possible inverse relationship between educational attainment and the development of dementia and the results of our study may have a role to play in this relationship. (AU)

Quantification of EEG waves in healthy persons and patients with brain disorders [abstract]

The biological processes that give rise to many disorders of the brain such as schizophrenia, depression and epilepsy are yet to be clearly explained. The electroencephalograms (EEG) from patients with these disorders have been reported to exhibit "chaotic" properties. Coarse-grained correlation dimension (Dcg) has been found to be an effective tool in analyzing waveforms with chaotic properties. We therefore tested the hypothesis that the Dcg of the EEG of patients with the above disorders will be different from those of healthy volunteers. Twenty-five minutes of EEG recordings were obtained from different regions of the brain of 20 healthy volunteers, seven patients with schizophrenia, one with depression, and one with partial seizure. Each person's EEG was edited to obtain 51 seconds of artifact-free recording. A software was developed in-house and used to obtain estimates of the Dcg. A confidence interval for each of the 21 EEG electrode points was established for the healthy volunteers (control group). Compared to the control group, the Dcg measurements of some of the schizophrenics, of the depressed patients, and that of the epileptics showed significant differences (p< 0.005). The results of this study indicate that the Dcg of the EEG for some brain disorders may be of use in the diagnosis of these conditions. Given the preliminary nature of this study, further work with larger sample sizes will be necessary in order to determine the reliability and sensitivity of this method. (AU)

Activation of AMPA receptors in the cerebral cortex may be protective against migraine headache [abstract]

The pathogenesis of migraine involves a spreading depression of neurons in the cerebral cortex resulting from over-excitation by released neurotransmitters or electrolytes. Glutamic acid is the most common excitatory neurotransmitter in the brain and spinal cord of mammals. Analogues of glutamic acid including AMPA (DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-asparatic acid) act on different receptors to depolarize the neurons of the cerebral cortex. Previous work has shown that evoked electrical potentials recover from the effects of NMDA on this neuronal network, suggesting a form of neuronal desensitization or network adaption. We have extended these observations by examining the effects of AMPA in the cerebral cortex, the interactions between AMPA and NMDA and the interactions between AMPA and spreading depression. Male Sprague-Dawley rats were anaesthetized with urethane and potentials evoked at the cortical surface by electrical stimulation of the contralateral forepaw. The compounds were applied topically to the cortex by a cortical cup. NMDA at 0.05-0.25mM caused a concentration-dependent decrease in the amplitude of the potentials, with the highest concentration always abolishing them. AMPA at 0.05mM did not affect the evoked potentials when applied alone, but when 0.25mM NMDA was preceeded by an application of AMPA, the latter prevented the NMDA effects in a concentration-dependent manner. Such AMPA-NMDA interactions were inhibited by CNQX (6-cyano-7-nmitroquinoxalinne-2, 3-dione, an antagonist of AMPA) and ehanced by cyclothiadize (which prevents AMPA desensitization). Topical application of AMPA, (0.5mM) prevented the electrophysiological manifestation of spreading depression in the cerebral cortex. Chlormethiazole, a GABA-mimetic drug that is known to prevent epileptic seizures, at 0.2-2mM, was not effective in preventing the spreading depression. These results suggest that, in the rate cerebral cortex, activation of the AMPA receptor (a glutamic acid receptor subtype) can induce a loss of neuronal response to activation of another glumatic acid receptor subtype, the NMDA receptor. Also, activation of the AMPA receptor in the cerebral cortex seems to have a neuroprotective role against the spreading depression that has been implicated in migraine. (AU)

Neuroprotection by caffeine and pentoxifylline during experimental cerebral ischaemia

Cerebral ischaemia was induced in anaesthetized rats by occlusion of the ipsilateral common carotid and middle cerebral arteries. The response to ischaemia was assessed by the reduction of the amplitude of recorded somatosensory evoked potentials (SSEPs), and the rate of recovery of the SSEPs during reperfusion. Caffeine and pentoxifylline when applied at 70 mM to the cortex for 60 min prior to induction of ischaemia significantly reduced the ischaemia induced attenuation of the SSEPs and hastened recovery to control levels. In contrast, application of normal saline or of the drugs for 15 min did not reduce the effect of ischaemia on the SSEPs. These results suggest that caffeine and pentoxifylline have potential roles in the management of patients with cerebral ischaemia.(AU)

Evaluation of a home kit blood glucose monitoring device

A blood glucose monitoring device, the *Diascan, is commonly used in Trinidad and Tobago. A prospective study was conducted to examine the accuracy of a Diascan unit in measuring blood glucose levels in or capillary venous blood of patients in a hospital ward. The Diascan measurements were compared to those from two laboratories which independently measured the venous blood or the venous plasma glucose levels. Although there was reasonably good correlation between measurements from the two laboratories (r=0.85) results from the Diascan showed poor correlations with those from the laboratories, with Pearson's correlation coefficients ranging from 0.32 to 0.64. An error grid analysis showed that the Diascan measurements would have resulted in inappropriate decisions relating to treatment regimens in 26 percent of cases. The results suggest that, when crucial deisions have to be made with respect to patients' blood glucose levels, it may be risky to rely solely on measurements from the Diascan.(AU)