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Biomedical subjects

Y Amitai

Publications and source records attributed to Y Amitai.

At least 19 recordsLinked to original sources
PubMed1998

Neuropsychological impairment from acute low-level exposure to carbon monoxide.

OBJECTIVE: To investigate the effects of acute low-level exposure to carbon monoxide on higher cognitive functions in healthy humans. DESIGN: An empirical study of the effects of low-level exposure to carbon monoxide on higher cognitive functions in young healthy volunteers and a matched nonexposed control group. SETTING: A dormitory at the Hebrew University campus in Jerusalem, Israel. PARTICIPANTS: Forty-five student volunteers who were exposed to carbon monoxide from residential kerosene stoves for 1.5 to 2.5 hours (air carbon monoxide concentrations of 17-100 ppm; mean +/- SD, 61 +/- 24 ppm) served as the experimental group and 47 nonexposed students served as the control group. MAIN OUTCOME MEASURES: A battery of neuropsychological tests was administered to each participant including digit span, the revised Wechsler Memory Scale for verbal and figural memory, Trail-Making Test parts A and B, digit symbol, block design, and the Rey Auditory Verbal Learning Test. RESULTS: Venous blood carboxyhemoglobin (Hbco) levels in participants of the study group ranged from 0.01 to 0.11 (mean +/- SD, 0.04 +/- 0.03) and correlated with air carbon monoxide concentrations (r = 0.39; P = .01). The experimental group scored significantly lower than controls on the following tests: digit span forward (P = .02), short-term (P = .008) and long-term semantic memory (P = .008), digit symbol (P = .004), block design (P = .009), recall of figural memory (P = .02), and Trail-Making part A (P = .04). No significant differences were found between the experimental and control groups in other tests. CONCLUSIONS: The lower scores on neuropsychological tests indicate dysfunctions in memory, new learning ability, attention and concentration, tracking skills, visuomotor skills, abstract thinking, and visuospatial planing and processing. These dysfunctions correspond with previous reports of carbon monoxide neurotoxic effects in patients with moderate carbon monoxide poisoning. Low-level exposure to carbon monoxide results in impairment of higher cognitive functions. Neuropsychological testing appears to be sensitive in the detection of subtle neurologic dysfunctions resulting from carbon monoxide poisoning.

Adult↗
PubMed1997

Differential regulation of neocortical synapses by neuromodulators and activity.

Synapses are continually regulated by chemical modulators and by their own activity. We tested the specificity of regulation in two excitatory pathways of the neocortex: thalamocortical (TC) synapses, which mediate specific inputs, and intracortical (IC) synapses, which mediate the recombination of cortical information. Frequency-sensitive depression was much stronger in TC synapses than in IC synapses. The two synapse types were differentially sensitive to presynaptic neuromodulators: only IC synapses were suppressed by activation of GABA(B) receptors, only TC synapses were enhanced by nicotinic acetylcholine receptors, and muscarinic acetylcholine receptors suppressed both synapse types. Modulators also differentially altered the frequency sensitivity of the synapses. Our results suggest a mechanism by which the relative strength and dynamics of input and associational pathways of neocortex are regulated during changes in behavioral state.

Animals↗
PubMed1997

Propagating neuronal discharges in neocortical slices: computational and experimental study.

We studied the propagation of paroxysmal discharges in disinhibited neocortical slices by developing and analyzing a model of excitatory regular-spiking neocortical cells with spatially decaying synaptic efficacies and by field potential recording in rat slices. Evoked discharges may propagate both in the model and in the experiment. The model discharge propagates as a traveling pulse with constant velocity and shape. The discharge shape is determined by an interplay between the synaptic driving force and the neuron's intrinsic currents, in particular the slow potassium current. In the model, N-methyl-D-aspartate (NMDA) conductance contributes much less to the discharge velocity than amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) conductance. Blocking NMDA receptors experimentally with 2-amino-5-phosphonovaleric acid (APV) has no significant effect on the discharge velocity. In both model and experiments, propagation occurs for AMPA synaptic coupling gAMPA above a certain threshold, at which the velocity is finite (non-zero). The discharge velocity grows linearly with the gAMPA for gAMPA much above the threshold. In the experiments, blocking AMPA receptors gradually by increasing concentrations of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in the perfusing solution results in a gradual reduction of the discharge velocity until propagation stops altogether, thus confirming the model prediction. When discharges are terminated in the model by the slow potassium current, a network with the same parameter set may display discharges with several forms, which have different velocities and numbers of spikes; initial conditions select the exhibited pattern. When the discharge is also terminated by strong synaptic depression, there is only one discharge form for a particular parameter set; the velocity grows continuously with increased synaptic conductances. No indication for more than one discharge velocity was observed experimentally. If the AMPA decay rate increases while the maximal excitatory postsynaptic conductance (EPSC) a cell receives is kept fixed, the velocity increases by approximately 20% until it reaches a saturated value. Therefore the discharge velocity is determined mainly by the cells' integration time of input EPSCs. We conclude, on the basis of both the experiments and the model, that the total amount of excitatory conductance a typical cell receives in a control slice exhibiting paroxysmal discharges is only approximately 5 times larger than the excitatory conductance needed for raising the potential of a resting cell above its action potential threshold.

Animals↗
PubMed1997

Bradycardia in toluene poisoning.

BACKGROUND: Tachyarrhythmias are the classical manifestation of toluene cardiotoxicity. The presumed mechanism is sensitization of the myocardium to the potential arrhythmogenic effect of endogenous catecholamines, occasionally resulting in fatality. Bradyarrhythmias have been repeatedly shown in animal models, but have been reported only once in a human. CASE REPORTS: Two patients with toluene intoxication presented with severe sinus bradycardia. One patient had also atrial-ventricular dissociation. In both cases cardiac rhythm returned to normal within several hours. CONCLUSION: We suggest that the spectrum of cardiotoxic symptoms associated with toluene intoxication in humans includes bradyarrhythmias as well as tachyarryhthmias.

Adult↗
PubMed1996

Properties of convergent thalamocortical and intracortical synaptic potentials in single neurons of neocortex.

We explored differences in the properties of convergent afferent inputs to single neurons in the barrel area of the neocortex. Thalamocortical slices were prepared from mature mice. Recordings were made from neurons in layer V, and either thalamocortical afferents or horizontal intracortical axons were stimulated. Monosynaptic EPSPs from both sources had latencies shorter than 1.8 msec and low shape variance. Disynaptic thalamocortical IPSPs had latencies longer than 1.8 msec. All neuronal types, as defined by intrinsic firing patterns, received both thalamocortical and intracortical monosynaptic input. The shape parameters (rate of rise and half-width) of monosynaptic EPSPs from the two inputs did not differ significantly. The rate of rise of EPSPs varied considerably across cells, but the rates of rise of thalamocortical and intracortical EPSPs onto single cells were strongly correlated. The relative thresholds for activation of synaptic excitation and inhibition were strikingly different between the two tracts: thalamocortical stimulation induced GABAA-dependent IPSPs at stimulus intensities equal to or less than those required for evoking EPSPs in 35% (24 of 68) of the cells. In contrast, the threshold response to intracortical stimulation was always an EPSP, and only stronger stimuli could generate di- or polysynaptic IPSPs. We suggest that postsynaptic factors may tend to equalize the waveforms of EPSPs from thalamocortical and intracortical synapses onto single neurons. A major difference between the two convergent tracts is that the thalamocortical pathway much more effectively activates feedforward inhibitory circuits than does the horizontal intracortical pathway.

Animals↗
PubMed1996

Glucose-6-phosphate dehydrogenase deficiency severely restricts the biotransformation of daunorubicin in human erythrocytes.

Recognition and analysis of distinct mechanisms by which primaquine and other hemolytic drugs activate the hexose monophosphate shunt (HMS) have suggested a hitherto unsuspected pharmacogenetic interaction between daunorubicin metabolism and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Because this deficiency is very common, and because anthracyclines are indispensable antitumor antibiotics that are biotransformed mainly by carbonyl reductase, we have compared the reductase-mediated conversion of daunorubicin to daunorubicinol and the conversion of doxorubicin to doxorubicinol in G6PD-deficient and nondeficient erythrocytes. We found that even without G6PD deficiency, the HMS dehydrogenases selectively limited daunorubicin metabolism, as contrasted with that of doxorubicin. The milder GdA- variety of G6PD deficiency restricted the biotransformation of daunorubicin at therapeutic levels, in hemolysates and intact erythrocytes, within 15 minutes, for at least 24 hours. The bioconversion defect was even more severe in Gd Mediterranean G6PD deficiency. Primaquine aldehyde competed with daunorubicin as a substrate for carbonyl reductase. These studies show that HMS dehydrogenase activity controls carbonyl reductase-dependent biotransformation. New issues arise concerning possible effects of G6PD deficiency on the oncolytic and toxic properties of anthracyclines that are effective substrates for carbonyl reductase and also on non-xenobiotic reactions catalyzed by this enzyme.

Adult↗
PubMed1996

Adult thalamocortical transmission involves both NMDA and non-NMDA receptors.

1. The involvement of N-methyl-D-aspartate (NMDA) receptors in thalamocortical transmission has been demonstrated in early postnatal development, but could not be determined so far in adult animals. We used thalamocortical slices from brains of mature mice to examine whether NMDA receptors exist in adult thalamocortical synapses, and what is their potential contribution to thalamocortical synaptic responses. 2. Thalamocortical fibers to the primary somatosensory area of the cortex were stimulated by an electrode placed in the ventrobasal (VB) nucleus of the thalamus. Horizontal intracortical axons within layer 5 were stimulated for comparison: a cut was made in the slice between layers 4 and 5 lateral to the recording area, and a second stimulating electrode was placed under the cut to activate these fibers. 3. Mg(2+)-free perfusing solution was used to enhance NMDA-receptor-mediated excitatory postsynaptic potentials (EPSPs). It led to synchronized population events that could be evoked by stimulating either in the thalamus or in layer 6. A short-latency, monosynaptic EPSP preceded the synchronous events in layer 5 cells. 4. Bath application of the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) abolished only synchronized events triggered from the thalamus, but not intracortically. CNQX reduced, but did not abolish, the monosynaptic thalamocortical EPSP, and had almost no effect on intracortically evoked EPSPs. Focal application of the gamma-aminobutyric acid-A receptor antagonist bicuculline methiodide (10 microM) to layer 4 reestablished the appearance of synchronous events on thalamic stimulation. 5. Monosynaptic thalamocortical and intracortical EPSPs on the same cells were studied in the presence of normal Mg2+ concentration to mimic better the physiological state. Spikes were abolished by intracellular injection of the quarternary lidocaine derivative (QX-314) sodium channel blocker. EPSPs from both sources were reduced compared with control, but not blocked, after bath application of CNQX (10 microM). CNQX-resistant EPSPs of both synaptic tracts were evident at membrane potentials close to rest, exhibited strong voltage dependency, and were blocked by the NMDA antagonist DL-2-amino-5-phosphonovaleric acid (APV), suggesting that they were NMDA receptor dependent. 6. To confirm that NMDA receptors were indeed activated at thalamocortical synapses and not by antidromic activation of intracortical pathways, we used pressure microapplications of glutamate (10 mM) to the VB nucleus of the thalamus. The perfusing solution contained CNQX (10 microM) and cells were recorded with micropipettes containing QX-314. All cells that showed a monosynaptic response to electrical thalamic stimulation also exhibited a barrage of mixed synaptic responses to thalamic glutamate application. The amplitude of these synaptic events was dependent strongly on the membrane voltage, and the application of APV to the cortex abolished the events completely. 7. Our results demonstrate that, in adult animals, both thalamocortical and intracortical synaptic pathways utilize NMDA as well as non-NMDA receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1996

Chloral hydrate toxicity from oral and intravenous administration.

BACKGROUND: Overdose from enteric chloral hydrate results in cardiovascular and central nervous system symptoms. CASE REPORTS: This case series compares and contrasts two cases of oral chloral hydrate overdose with two cases of accidental i.v. administration. Whereas ingestion of 219 mg/kg of chloral hydrate resulted in transient bigeminy, ingestion of up to 960 mg/kg caused torsades de pointes and ventricular fibrillation which were effectively treated with defibrillation and a beta blocker. I.V. administration in humans does not appear previously documented. Two cases of i.v. administration of a therapeutic chloral hydrate dose resulted in central nervous system depression and minimal local effects at the injection site. CONCLUSIONS: Given the high bioavailability of oral chloral hydrate the major determinant of cardiotoxicity may be the dose rather than the route of administration. Cardiac arrhythmias due to chloral hydrate appear to be responsive to beta blocker therapy.

Administration, Oral↗
PubMed1995

Beneficial effect of digoxin-specific Fab antibody fragments in oleander intoxication.

A 24-year-old man presented to the emergency department with nausea, vomiting, abdominal pain, and an acute confusional state of 6 hours' duration. Ten hours before admission, he had ingested a mixture of orange juice and six ground leaves, later identified as Nerium oleander (common pink oleander) leaves. His blood pressure was 100/80 mm Hg, and his pulse rate was irregular at 40/min. He was disoriented and his speech was dysarthric. Twelve-lead electrocardiography revealed a complete atrioventricular block, with a nodal escape rhythm of 40/min and diffuse ST depression. The presumptive diagnosis of acute oleander intoxication was confirmed by the detection of digoxin (1.0 nmol/L [0.8 ng/mL]) on radioimmunoassay. Despite intensive therapy, the patient's hemodynamic condition deteriorated. His blood pressure decreased to 70/40 mm Hg; he became oliguric and nonresponsive to external stimuli; and his potassium concentration rose to 6.8 mmol/L. Eighteen hours after admission, an empiric 480-mg dose of digoxin-specific Fab antibody fragments was administered intravenously over 30 minutes. Within minutes of the initiation of immunotherapy, the patient woke up; his blood pressure rose to 90/50 mm Hg; and he regained a sinus rhythm of 68/min with a prolonged PR interval. His potassium concentration decreased to 5.1 mmol/L within 15 minutes and normalized within 1 hour of therapy initiation. One day later, the 1 degree atrioventricular block disappeared, but the ST depression persisted for an additional 6 days. The value of digoxin-specific Fab antibody fragments in the treatment of plant glycoside and, in particular, oleander intoxication is discussed.

Adult↗
PubMed1995

Cortical synchronized activity evoked by thalamocortical stimulation in vitro.

Epileptiform activity was studied in the thalamocortical (THC) slice preparation. Inhibition was gradually attenuated with increasing doses of bicuculline methiodide (BMI). We compared the ability of thalamic and intracortical (INC) stimulation to evoke epileptiform activity. Synchronized population activity was identified by its all-or-none appearance at a threshold stimulus intensity, by a variable latency and by horizontal propagation to large distances. For most slices (20 out of 24) we could establish a threshold dose of BMI (0.4-0.7 microM) under which THC-evoked population events had epileptiform properties, while INC-evoked ones did not. Increasing the BMI dose by 0.2 microM resulted in the appearance of epileptiform field potentials when stimulating intracortically. It is concluded that the tendency of the neocortex to generate synchronized population activity is higher when it is activated through the THC pathway.

Afferent Pathways↗
PubMed1995

Paresthesia in envenomation by the scorpion Leiurus quinquestriatus.

We observed two patients with systemic paresthesia as the sole systemic manifestation of envenomation by L. quinquestriatus. A prospective study of the incidence of local and systemic paresthesia in 20 consecutive patients stung by this scorpion was done. Sixteen patients (80%) had only local complaints and 4/20 (20%) had mild systemic manifestations. Eleven patients (55%) had local paresthesia and in 2 patients (10%) systemic paresthesia was noted involving all four extremities in one patient and the perioral area in the other. The possible mechanism of paresthesia following a scorpion sting is discussed.

Adult↗
PubMed1994

A comparison of synapses onto the somata of intrinsically bursting and regular spiking neurons in layer V of rat SmI cortex.

Regular spiking (RS) and intrinsically bursting (IB) neurons show distinct differences in their inhibitory responses. Under various conditions, the synaptic responses of RS cells display marked inhibitory postsynaptic potentials (IPSPs), whereas the responses of most IB cells do not (Silva et al: Soc Neurosci Abstr 14:883, 1988; Chagnac-Amitai and Connors: J Neurophysiol 61:747, 62:1149, 1989; Connors and Gutnick: TINS 13:99, 1990). This investigation is designed to determine if differences in the inhibitory responses of RS versus IB cells are reflected in differences in the concentration of inhibitory synapses onto their somata. RS and IB neurons in rat somatosensory cortex were identified by using intracellular recording and labeling, examined with the light microscope, and then serial thin-sectioned prior to examination with the electron microscope. Axonal terminals presynaptic to their somata and proximal dendrites were identified and classified according to criteria described by Peters and coworkers (Peters et al: J Neurocytol 19:584, 1990; Peters and Harriman: J Neurocytol 19:154, 1990; 21:679, 1992). The locations of these boutons were displayed on the surfaces of 3-D reconstructions of the somata and proximal dendrites. The reconstructions were produced directly from the serial thin sections by using a novel, electron microscopic, image-processing computer resource. Our analysis showed no significant difference in the types and concentration of boutons presynaptic to the cell bodies and proximal dendrites of intrinsically bursting versus regular spiking neurons. We conclude that the differences observed in the inhibitory responses of intrinsically bursting versus regular spiking neurons cannot be explained by differences in the concentrations of synapses onto their somata.

Action Potentials↗
PubMed1994

Membrane potential oscillations underlying firing patterns in neocortical neurons.

Membrane potential oscillations were studied in slices of rat somatosensory cortex maintained in vitro, using intracellular recordings from cells in layers 2/3 and 5. The cells were classified according to their firing patterns during long (0.8-1 s) depolarizing current steps. Subthreshold voltage oscillations were revealed by depolarizing the membrane to voltages around threshold for action potentials; however, these were obvious mainly in cells showing marked spike adaptation. When neurons of all firing patterns were stimulated to fire at 40-60 Hz for tens of seconds, spikes abruptly indicated. Hyperpolarizing the cells by 5-10 mV precipitated pronounced oscillations in 24 out of 35 cells. These oscillations existed in a narrow voltage range, and their frequency varied between 7 and 40 Hz, in a voltage-dependent manner. Spiking frequency was faster than the oscillation frequency for the same membrane potential in a given cell. The Na+ channel blocker tetrodotoxin abolished both the spikes and the oscillations, and blockade of K+ channels by tetraethylammonium converted the oscillations into prolonged and irregular plateaus. Blocking Ca2+ conductance with Co2+ reduced the oscillations amplitude and frequency in two out of three cells. The oscillations that followed spike inactivation varied in amplitude, frequency and persistence among different cells. Layer 5 nonadapting cells possessed the most periodic oscillations, as judged by autocorrelation analysis. Oscillations were also most persistent in this group, maintaining a stable steady-state. In other cell types, the oscillations were less regular and decayed with time. There was no difference among cell groups in the maximal peak to peak amplitude of the oscillations, or their frequency range. It is suggested that the oscillations are generated by ionic conductances that operate within the voltage range just above and below spike threshold, and thus can shape the cells' firing pattern. The prominence of the oscillations in a specific subset of layer 5 cells may indicate the mechanism that underlies the rhythmic firing pattern of those cells.

Animals↗
PubMed1993

Injection of tetanus toxin into the neocortex elicits persistent epileptiform activity but only transient impairment of GABA release.

Focal injection of a minute quantity of tetanus toxin into the rat neocortex induces chronic epileptogenesis. Within a day, spontaneous and stimulus-evoked paroxysmal discharges appear in widespread regions of both hemispheres and this lasts for at least nine months. Tetanus toxin blocks transmitter release, apparently by catalysing the breakdown of synaptobrevin, a synaptic protein. It specifically binds to neuronal membranes but its potent epileptogenic properties have been ascribed to a higher affinity for inhibitory neurons. Following focal injection of tetanus toxin into the hippocampus a long-lasting epileptic syndrome also develops. During the early part of the syndrome GABA release is depressed in slices from the injected side, but not in slices from the contralateral, secondary focus. In the present experiments on neocortex, release of radiolabelled GABA was measured from primary and secondary epileptic foci induced by unilateral focal injection of tetanus toxin into the parietal cortex. By four weeks after the injection, no differences were detected in GABA release from any neocortical site in control or toxin-injected animals, despite the persistence of profound epileptic activity in slices from the latter. At earlier times (1.5 days) after the toxin injection, however, release was significantly depressed in both hemispheres. The results indicate that at first, the toxin induces focal neocortical epileptogenesis by directly impeding GABAergic synaptic transmission but that with time there is a recovery from this initial effect. We propose, as has also been suggested for other models, that the initial epileptogenesis leaves in its wake a long-lasting change in the local functional connectivity, such that the neocortex is rendered permanently epileptic.

Animals↗
PubMed1993

Tricyclic antidepressants in red cells and plasma: correlation with impaired intraventricular conduction in acute overdose.

OBJECTIVE: Tricyclic antidepressant levels in red blood cells and plasma in acute overdose and their association with cardiotoxicity were studied. METHODS: This was a prospective study in 15 patients with acute tricyclic antidepressant overdose. Tricyclic antidepressant parent compounds and metabolites were measured in red blood cells and plasma, and tricyclic antidepressant levels were correlated with ECG indexes of toxicity. RESULTS: Plasma levels of the parent compounds were higher than their red blood cell levels on admission (mean +/- SD, 691 +/- 409 and 337 +/- 220 ng/ml, respectively). Admission metabolite levels were higher in red blood cells than in plasma (264 +/- 180 and 190 +/- 164 ng/ml, respectively). QRS duration and the red blood cell levels of the metabolites were significantly correlated at the time of admission (r = 0.77, p < 0.01), as well as at 6 to 10 hours (r = 0.74, p < 0.01). CONCLUSIONS: In acute overdose, a shift of tricyclic antidepressants from plasma to red blood cells and increased levels of red blood cell metabolites reflect tissue redistribution of the drug. Tricyclic antidepressant red blood cell metabolites are the best markers for impaired intraventricular conduction.

Adolescent↗