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Biomedical subjects

T Dalkara

Publications and source records attributed to T Dalkara.

At least 55 records · Page 3Linked to original sources
PubMed1993

Myasthenia gravis and primary squamous cell carcinoma of the thymus.

Occurrence of primary squamous cell carcinoma of the thymus gland in a 65-year-old man with myasthenia gravis is reported. Histologic and immunohistochemical studies confirmed the diagnosis of a differentiated squamous cell carcinoma. Extensive clinical investigations ruled out another primary site for the tumor. The patient made a full recovery postoperatively. Only three cases of primary squamous cell carcinoma of the thymus gland in association with myasthenia gravis have been reported in the literature.

Aged↗
PubMed1992

Glycine is required for NMDA receptor activation: electrophysiological evidence from intact rat hippocampus.

Fimbrial/commissural stimulation evokes a prolonged negative field potential in stratum radiatum of CA1 region of the rat hippocampus, in situ, upon activation of N-methyl-D-aspartate (NMDA) receptors. This activity can be induced by iontophoresis of NMDLA (50 nA) or glycine (50-100 nA) during low-frequency stimulation. 7-Cl-Kynurenate (10-30 nA) fully antagonized the NMDA receptor-mediated negative wave induced not only by glycine (N = 3) but also by NMDLA (N = 9), suggesting that activation of NMDA receptors is not possible without glycine binding. 7-Cl-Kynurenate also depressed the extracellular negative d.c. potential shifts appearing during iontophoresis of NMDLA. Stimulation with brief, high-frequency trains evoked a negative wave of 2.1 +/- 0.2 mV and 176 +/- 4 ms (N = 20) on the hippocampal field response following the last stimulus. Ketamine (100-200 nA, N = 6) and MK-801 (50-200 nA, N = 7) blocked the negative wave by 74 +/- 13 and 62 +/- 8%, respectively, while glycine (100 nA) potentiated it by 35 +/- 2% (N = 6), indicating that it had a component mediated by NMDA receptors. 7-Cl-Kynurenate (100 nA) antagonized this activity at a comparable rate to the NMDA receptor antagonists (67 +/- 8%, N = 4). A similar negative wave of 0.9 +/- 0.2 mV and 41 +/- 3 ms (N = 12) was evoked in hippocampal slices by high-frequency orthodromic stimulation. Potentiation of this activity upon lowering Mg2+ in ACSF from 1.3 to 0.5 mM further supported that it had an NMDA-mediated component.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

High dose anticholinergic therapy (biperiden) in dystonia.

We studied the effect of biperiden in the treatment of dystonia in six patients aged 15-30 years. Five patients had generalized and one patient had segmental dystonia. Biperiden was started at a dose of 2 mg/day and was gradually increased to 40 mg/day in a few weeks. All patients had clinically significant response in varying degrees after a mean follow up of 1.9 years. Three patients showed considerable or dramatic benefit. The 40 mg/day was generally well tolerated. High dose anticholinergic therapy is effective in the management of torsion dystonia.

Adolescent↗
PubMed1991

Formulation, bioavailability, and pharmacokinetics of sustained-release potassium chloride tablets.

The release of potassium chloride incorporated into hydrogenated vegetable oil and hydroxypropyl methylcellulose matrix tablets was studied in vitro. The formulations containing 20% hydrogenated vegetable oil and hydroxypropyl methylcellulose showed a sustained-release profile comparable to that of a standard commercially available sustained-release preparation, containing 8 mEq potassium chloride embedded in a wax material. The formulated and standard sustained-release potassium chloride tablets were compared to a conventional enteric-coated potassium chloride tablet in 10 healthy subjects. Mean recoveries in 24-hr urine potassium levels from four dosage forms (after subtracting normal urine potassium excretion levels) were 76 +/- 32% from hydroxypropyl methylcellulose, 95 +/- 22% from hydrogenated vegetable oil-incorporated matrix tablets, 91 +/- 29% from commercially available sustained-release tablets, and 97 +/- 13% from enteric-coated tablets. There was no significant difference (P greater than 0.05) in the time to reach maximum excretion rates among the three sustained-release tablets. No significant adverse effect was experienced with any of the preparations.

Adult↗
PubMed1990

Electrophysiological evidence for activation of NMDA receptors and its antagonism by MK-801 in cerebral ischemia.

We studied the effects of iontophoretically administered MK-801 (50-150 nA) on ischemic changes on the CA1 hippocampal field potential. Twenty rats under urethane anesthesia, of which the hippocampal field response was depressed or lost upon ligation of the carotid arteries, were used. MK-801 applications starting before carotid ligation, decreased the depression of the field response in 8 of 11 trials. MK-801 was applied after the appearance of ischemic changes and partly restored the deteriorated hippocampal field potential in 16 of 34 penetrations. MK-801 was ineffective in preventing or restoring the severely depressed or lost evoked activity. During ischemia a DC potential shift of -32.6 +/- 3.7 mV (n = 10) was recorded. MK-801 reduced the amplitude of the DC potential shift by 50% when applied before (n = 6) or after (n = 4) the initiation of ischemia. Activation of N-methyl-D-aspartate (NMDA) receptors by glutamate or N-methyl-DL-aspartate (NMDLA) induces a slow negative wave on the field response. During ischemia a similar negative wave spontaneously appeared in 9 trials and was also induced with low currents (5-10 nA) of NMDLA which were insufficient to evoke the NMDA-mediated wave before ischemia. These data provide electrophysiological evidence that NMDA receptors are activated during ischemia and MK-801 reduces ischemia neuronal dysfunction.

Animals↗
PubMed1990

Glutamate and glycine induce a negative wave on hippocampal field response through NMDA receptors.

In rats under urethane anesthesia, iontophoresis of large amounts (30-300 nA) of glutamate in the hippocampus induced a negative wave on the field potential evoked by stimulation of fimbria/commissura or perforant pathway. The amplitudes of the negative waves ranged between 0.2 and 9.8 mV and their mean duration was 341 +/- 12 ms. This activity was antagonized by iontophoresis of N-methyl-D-aspartate (NMDA) antagonists: Mg2+ (80-100 nA), ketamine (50-150 nA), MK-801 (50-150 nA) and by systemic ketamine (5 mg/kg, i.v.) administration. Iontophoresis of N-methyl-DL-aspartate (NMDLA) (20-40 nA) and glycine (25-100 nA) also elicited a negative wave which was blocked by NMDA antagonists. The negative waves were induced in all hippocampal layers except the dentate hilus by glutamate, NMDLA and glycine. Pyramidal regions were found to be as sensitive as dendritic layers; the mean amplitudes of glutamate-induced negative waves on the field response were 4.1 +/- 0.6 and 4.2 +/- 0.5 mV for CA1 stratum pyramidale and radiatum, respectively. These data suggest that large amounts of glutamate activate NMDA receptor/ion channels causing appearance of a long-lasting negative wave on the hippocampal field response. The data also demonstrate that glycine leads to a significant participation of NMDA receptors during glutamatergic transmission which is largely mediated through non-NMDA receptors.

Animals↗
PubMed1990

Acute idiopathic demyelinating polyneuropathy: passive transfer to mice by immunoglobulin.

Systemic administration of acute idiopathic demyelinating polyneuropathy (AIDP) immunoglobulins to mice for two weeks resulted in reduced sural nerve action potential amplitudes and reduced (rotarod) motor performance. Electron microscopic examination of the sciatic nerves of the AIDP-immunoglobulin-treated animals revealed loosening of myelin lamellae with widening of interperiod lines and multivesicular disruption of myelin. Vacuolar degeneration was detected in half of the nerves examined by light microscopy. Injection of AIDP-immunoglobulins for three days led to only minor changes, and mice receiving healthy human immunoglobulins showed no abnormalities. These data show that some features of AIDP can be transferred to mice by systemic administration of immunoglobulins and suggest that humoral factors have a pathogenic role in AIDP in addition to cellular factors.

Action Potentials↗
PubMed1989

Glutamate, without GABA antagonists, induces synchronized discharges in intact hippocampus via NMDA receptors.

In rats under urethane anesthesia, iontophoresis of high amounts of glutamate (50-150 nA) in hippocampus caused repetitive field potentials. These synchronized discharges were best recorded in the proximal part of stratum radiatum as positive waves of 10-15 ms duration and of 0.5-5 mV amplitude. A tetrodotoxin-sensitive faster component of 2-5 ms duration was frequently superimposed on the peaks of the positive waves and was followed by a negative wave of 1-6 mV and 20-30 ms. Glutamate-evoked discharges were suppressed by iontophoresis of N-methyl-D-aspartate (NMDA) antagonists, MK-801, Mg2+ and ketamine and also by ketamine injection (i.v. 5-10 mg/kg). The population spikes evoked by fimbrial stimulation were not facilitated by glutamate and the synchronized discharges were suppressed for up to 300 ms following the stimulation, suggesting the presence of an efficient inhibition during glutamate-induced synchronized activity. Glutamate also had no effect on paired-pulse inhibition. No synchronized discharges were recorded with a second electrode separated more than 150 microns from the iontophoretic electrode, suggesting that the activity was local. These data demonstrate that high amounts of glutamate evoke synchronized discharges in hippocampus, possibly through activation of NMDA receptors. The model presented may be utilized to study the mechanisms of synchronization without disinhibition.

Action Potentials↗
PubMed1989

Intravenously and iontophoretically administered naloxone reverses ischemic changes in rat hippocampus.

Forty rats under urethane anesthesia were subjected to cerebral ischemia by ligation of the right carotid, the right plus the left carotid, or the right carotid plus two vertebral arteries. Ischemia caused three types of changes in the field potential of the right hippocampal CA1 region evoked by fimbrial stimulation: 1) completely reversible deterioration (57% and 16% of the rats with unilateral and bilateral carotid artery ligation, respectively), 2) moderate deterioration (37% and 24% of the rats with unilateral and bilateral carotid artery ligation) and 3) irreversible loss of the evoked activity (6% and 60% of the rats with unilateral and bilateral carotid artery ligation and all the rats subjected to three-vessel occlusion). Naloxone improved the moderate deterioration in 10 of 11 rats (1-3 mg/kg i.v.) and in 15 of 16 (50-150 nA) iontophoretic applications, but naloxone did not restore the lost evoked activity. Intravenous morphine (10 mg/kg) aggravated the ischemic changes, and this effect was reversed by naloxone, while iontophoretic administration of morphine caused only excitation. These findings suggest that naloxone has a favorable effect on cerebral ischemia not severe enough to cause transmission failure. The reversal of ischemic changes by iontophoretic naloxone indicates that its site of action is at the neuronal or microcirculatory level.

Animals↗
PubMed1987

Facilitatory effects of dexamethasone on neuromuscular transmission.

The beneficial effects of glucocorticoids in myasthenia gravis are attributed to their immunosuppressive actions. There are also studies reporting direct facilitatory as well as depressant effects of glucocorticoids on neuromuscular transmission. The effects of dexamethasone on neuromuscular transmission were studied by intracellular and extracellular microelectrode recording techniques in the mouse phrenic nerve-diaphragm preparation. Creatinine had to be added to the bathing media to prevent precipitation of the glucocorticoid with Ca2+ and Mg2+; creatinine had no effect. One hour of perfusion with dexamethasone (10(-4) to 10(-3) M) increased the frequency of miniature end-plate potentials (MEPPs), as well as the amplitude and quantum content of end-plate potentials (EPPs), but did not change MEPP amplitude, suggesting an increase in acetylcholine release. Dexamethasone also enhanced presynaptic facilitation and potentiation during repetitive stimulation. It had no effect on muscle resting membrane potential but increased the amplitude, overshoot, and rate of rise of muscle action potentials. The amplitudes of nerve terminal action potentials were also enhanced by dexamethasone. These findings suggest that glucocorticoids have a direct facilitatory action on neuromuscular transmission by a presynaptic action.

Acetylcholine↗
PubMed1987

Calcium channel blockers and essential tremor.

Acute effects of two calcium blockers, nifedipine and verapamil, were investigated on the tremor activity of 8 patients with essential tremor and compared with those of propranolol and placebo. Following a single oral dose of 10 mg of nifedipine, tremor intensity of the patients was increased by 71.4 +/- 22.6%. Nifedipine also enhanced physiological tremor in 6 healthy volunteers by 56.0 +/- 21.9%. This effect of nifedipine was not correlated with the increase in heart rate or decrease in systemic blood pressure. Verapamil (80 mg) did not appreciably alter the patients' tremor activity.

Adult↗
PubMed1986

Iontophoretic studies on rat hippocampus with some novel GABA antagonists.

Twelve substances which appear to be GABA antagonists, judging by their ability to reverse the inhibitory effect of GABA on 35S-TBPS binding to rat brain membranes, were tested iontophoretically on population spikes in the rat hippocampus. Eight of them, including seven which completely reversed the inhibitory action of GABA on 35S-TBPS binding, caused a marked enhancement of population spikes, with slow onset and long duration and they antagonized the inhibition of population spikes by GABA. These effects were similar to those produced by bicuculline. Electrophysiologically, the most potent of the "complete reversers" were bathophenanthroline disulfonate and brucine. In vitro, amoxapine and brucine most effectively reversed the inhibitory action of GABA on 35S-TBPS binding. Of the five substances which only partly reversed the inhibitory effect of GABA on 35S-TBPS binding, four depressed the population spikes and potentiated the inhibitory action of GABA. The fifth "partial reverser", pipazethate, potently increased the population spikes, like the "complete reversers". Although other interpretations are possible the results are consistent with the existence of several GABA-A receptor types in brain, only some of which are blocked by certain partial reversers.

Action Potentials↗
PubMed1986

Nipecotic acid, an uptake blocker, prevents fading of the gamma-aminobutyric acid effect.

In rats under urethane, iontophoretic applications of GABA (30-60 nA) in the str. pyramidale of CA1, showed a rapidly fading inhibitory effect. By contrast, GABA had a well-maintained inhibitory effect in str. radiatum. During iontophoresis of nipecotic acid (30-85 nA) identical applications of GABA in str. pyramidale caused a more prominent depression without fading, which suggests that removal of GABA, by uptake, can at least in part account for 'fading'. Nipecotic acid also prolonged the paired-pulse inhibition, presumably by prolonging the duration of inhibitory postsynaptic potentials.

Animals↗
PubMed1986

Chemical modulation of ephaptic activation of CA3 hippocampal pyramids.

In rats under urethane anaesthesia, antidromic population spikes were evoked in CA3 pyramidal layer by fimbrial/commissural stimulation at a very low frequency (approximately 0.5 Hz). Submaximal population spikes--between 20 and 90% of maximum--were enhanced by 8-38% by applications of acetylcholine and bicuculline, or by medial septal stimulation. Noradrenaline had a less pronounced and regular facilitatory action, whereas gamma-aminobutyrate and glutamate only depressed population spikes. Maximal enhancement by acetylcholine or bicuculline was observed when the antidromic population spike was initially at 38-53% of maximum amplitude. A simple explanation of these results is that acetylcholine and bicuculline, by raising their excitability, facilitate the excitation of non-invaded pyramidal cells by antidromic field potentials. They are fully in keeping with previous intracellular observations on ephaptic interactions between CA3 neurons, and provide a further illustration, in situ, of the importance of increased excitability and disinhibition--whether caused by drugs or synaptic action--in promoting synchronized excitation by ephaptic currents.

Acetylcholine↗
PubMed1986

Ephaptically generated potentials in CA1 neurons of rat's hippocampus in situ.

Passive (ephaptic) transmembrane currents generated by antidromically evoked electrical fields were studied in CA1 hippocampal neurons of urethan-anesthetized rats. Recording was mostly from the stratum pyramidale where the fields have a maximum (negative) amplitude. The antidromic population spike was consistently smaller when recorded inside a noninvaded neuron rather than extracellularly. This indicated a substantial transmembrane potential (Vm), which was revealed and quantified by subtracting from the intracellular record a just-extracellular one. In neurons that have spikes greater than or equal to 40 mV (mean 60 mV), the average Vm was 41.1% of the extracellular field (Ve; mean 6.7 mV). Typically, Vm was very brief (mean duration 1.1 ms), predominantly monophasic, and in a depolarizing direction. Though almost synchronous with Ve, the peak of Vm was most often delayed slightly. Its amplitude varied with the intensity of antidromic stimulation, bearing an approximately constant relation to Ve, and it was not markedly sensitive to large changes in membrane potential. Most of these features confirm its ephaptic nature. By contrast, no consistent Vm was recorded from unresponsive cells, presumed to be glia. When combined with subthreshold depolarizing pulses, antidromic fields increased the firing probability of cells not activated by the antidromic stimulus. The ephaptic nature of this excitation was indicated by its very short latency, too early to be of synaptic origin, a much greater jitter of spike latency than was seen with antidromic spikes, and its inability to follow repetitive stimulation at frequencies as low as 2 Hz. In addition, juxta-threshold ephaptic excitations showed the random patterns of firing and very steep relation to intensity of stimulation expected of single-unit responses to electrical stimulation. In general, much larger excitatory effects could be demonstrated in neurons that had a high threshold for antidromic activation. The correlation between Vm and the increase in firing probability (r = 0.85) was strongly positive. A significant excitatory effect was detectable with antidromic fields as small as 1 mV. These ephaptically generated transmembrane potentials are probably of functional significance, even under physiological conditions, particularly in promoting synchronized firing of CA1 neurons. In the APPENDIX, the predictions of a simple neuronal model as a lumped resistance and capacitance circuit are shown to agree quite well with the observations.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗