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R Kovács

Publications and source records attributed to R Kovács.

15 recordsLinked to original sources

Desynchronisation of spontaneously recurrent experimental seizures proceeds with a single rhythm.

Here we investigate the temporal properties of recurrent seizure-like events (SLEs) in a low-[Mg(2+)] model of experimental epilepsy. Simultaneous intra- and extracellular electric signals were recorded in the CA3 region of rat hippocampal slices whereby cytosolic [Ca(2+)] transients were imaged by fluorescence detection. Recurrence pattern analysis was applied to give a measure of synchrony of simultaneously recorded intra- and extracellular electric signals and the SLE frequencies were extracted by complex wavelet analysis. Slices from the juvenile, but not the young adult rats, displayed several high-amplitude triplets of electric and [Ca(2+)] transients, termed paroxysmal spikes, followed by an SLE. Occurrence of the full-blown SLE was associated with decreased synaptic activity between the paroxysmal spikes that were seen as incomplete SLE starting sequences. The time series of recurrent SLEs provide evidence for a single SLE rhythm as continuously declining from about 200 Hz to below 1 Hz at the onset and termination of SLE, respectively, with an intermediate spectral discontinuity, tentatively identified with the tonic/clonic transition. All other frequency components were the harmonics of the fundamental rhythm, whereby the gamma and the theta band oscillations were not detected as separate activities. Recurrence showed decreasing temporal synchrony of intra- and extracellular signals during the SLE, suggesting that coincidence is destroyed by the SLE. Blockade of gap junctions with 200 microM carbenoxolone ceased recurrent SLEs. Release of gap junction blockade shortened both SLEs and their tonic phase indicating that persistent changes occurred via an altered gap junction coupling. We conclude that the initially precise temporal synchrony is gradually destroyed during ictal events with a single rhythm of continuously decreasing frequency. Blockade of gap junction coupling might prevent epileptic synchronisation.

Animals↗

Coupling of electrical and metabolic activity during epileptiform discharges.

Changes in electrical activity, ionic microenvironments, and intracellular Ca concentration were measured during recurrent seizures induced by low Mg in slices and slice cultures. In both preparations, initial seizure-like events (SLEs) changed after some time into drug-refractory late recurrent discharges. In slice cultures, there was considerable cell loss in all hippocampal areas after 2 h of status epilepticus. During recurrent SLEs, the NAD(P)H autofluorescence declined, as did intramitochondrial calcium signals, indicating mitochondrial damage. At the same time, ethidium signals indicated increased radical oxygen species production. These alterations could be reduced by alpha-tocopherol, which also protected slice cultures against status epilepticus-induced cell death.

Animals↗

Influence of a Spirulina platensis biomass on the microflora of fermented ABT milks during storage (R1).

The objective of this research was to investigate the effect of a cyanobacterial (Spirulina platensis) biomass on the microflora of a probiotic fermented dairy product during storage at two temperatures. Spirulina-enriched and control (plain) fermented acidophilus-bifidus-thermophilus (ABT) milks were produced using a fast fermentation starter culture (ABT-4) as the source of Lactobacillus acidophilus (A), bifidobacteria (B), and Streptococcus thermophilus (T). Incubation took 6 h at 40 degrees C. As for the cyanobacterial product, the S. platensis biomass was added to the process milk during stirring at pH 4.5 to 4.6. Thereafter, the ABT-type fermented milks were cooled to 25 degrees C in ice water, filled into sterile, tightly capped centrifuge tubes, further cooled at 4 degrees C for 24 h, and then stored either at 15 degrees C for 18 d or at 4 degrees C for 42 d. Microbiological analyses and acidity measurements were performed at regular intervals. Our results showed that the counts of the starter organisms were satisfactory during the entire storage period at both temperatures applied in this research. The S. platensis biomass had a beneficial effect on the survival of ABT starter bacteria regardless of storage temperature. Postacidification was observed at 15 degrees C, whereas pH remained stable during refrigerated storage at 4 degrees C. The abundance of bioactive substances in S. platensis is of great importance from a nutritional point of view because thus the cyanobacterial biomass provides a new opportunity for the manufacture of functional dairy foods.

Animals↗

Low-[Mg2+]-induced Ca2+ fluctuations in organotypic hippocampal slice cultures.

We show here by whole field monitoring of free intracellular Ca2+ ([Ca2+]i), locally recorded field potential (fp) and external [Ca2+], that low-[Mg2+] induces seizure like events (SLEs) accompanied by simultaneous fluctuations of [Ca2+]i and [Ca2+]e in cultured hippocampal slices. Within a SLE, complex [Ca2+]e fluctuations are seen throughout phases of Ca2+ depletion (tonic) and Ca2+ recovery (clonic) of the extracellular space. Information theory entropy-based analyses revealed strong asymmetric associations of [Ca2+]i and [Ca2+]e kinetics. By contrast, signal-associations between SLEs were found to be weak and of symmetric nature distinguishing seizure-like and interictal events by extensive coupling and decoupling of [Ca2+]i and [Ca2+]e fluctuations, respectively.

Animals↗

Effects of barium on stimulus-induced rises of [K+]o in human epileptic non-sclerotic and sclerotic hippocampal area CA1.

In the hippocampus of patients with therapy-refractory temporal lobe epilepsy, glial cells of area CA1 might be less able to take up potassium ions via barium-sensitive inwardly rectifying and voltage-independent potassium channels. Using ion-selective microelectrodes we investigated the effects of barium on rises in [K+]o induced by repetitive alvear stimulation in slices from surgically removed hippocampi with and without Ammon's horn sclerosis (AHS and non-AHS). In non-AHS tissue, barium augmented rises in [K+]o by 147% and prolonged the half time of recovery by 90%. The barium effect was reversible, concentration dependent, and persisted in the presence of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), N-methyl-D-aspartate (NMDA) and gamma-aminobutyric acid [GABA(A)] receptor antagonists. In AHS tissue, barium caused a decrease in the baseline level of [K+]o. In contrast to non-AHS slices, in AHS slices with intact synaptic transmission, barium had no effect on the stimulus-induced rises of [K+]o, and the half time of recovery from the rise was less prolonged (by 57%). Under conditions of blocked synaptic transmission, barium augmented stimulus-induced rises in [K+]o, but only by 40%. In both tissues, barium significantly reduced negative slow-field potentials following repetitive stimulation but did not alter the mean population spike amplitude. The findings suggest a significant contribution of glial barium-sensitive K+-channels to K+-buffering in non-AHS tissue and an impairment of glial barium-sensitive K+-uptake in AHS tissue.

2-Amino-5-phosphonovalerate↗

Coupled intra- and extracellular Ca2+ dynamics in recurrent seizure-like events.

We considered the evolution of Ca2+ oscillation dynamics in recurrent seizure-like events. Dynamic system behaviour was characterized in the state space reconstructed from intra- and extracellular [Ca2+] fluctuations simultaneously measured in cultured rat hippocampal slices under low-[Mg2+] conditions. When associated in the seizure-like event, these fluctuations occurred on a restricted set, the attractor, embedded in the full state space with less than five degrees of freedom. Instantaneous relative phase differences indicated field potential-driven phase jumps locked onto seizure-like events. To account for recurrent dynamics, calculations were performed on different extensions of a model for Ca2+ oscillation. These identified bidirectional, asymmetrical coupling of extracellular with intracellular (cytosolic, Ca2+ store, mitochondrial) Ca2+ dynamics as critical in its development.

Animals↗

Uridine activates fast transmembrane Ca2+ ion fluxes in rat brain homogenates.

The excitatory actions of the pyrimidine nucleoside uridine, and the nucleotides UDP and UTP, as well as the purine nucleotide ATP, were studied by fluorescent labeling of Ca2+ and K+ ion fluxes on the time scale of 0.04 ms to 10s in resealed plasmalemma fragments and nerve endings from the rat cerebral cortex. Two phases of Ca2+ ion influx with onsets of a few milliseconds and a few hundred milliseconds, showing different concentration dependencies, agonist sequences and subcellular localizations were distinguishable. [3H]Uridine identified high (K(D) approximately 15 nM) and low affinity (K(D)approximately 1 microM) specific binding sites in purified synaptosomal membranes. Labeled uridine taken up by synaptosomes in a dipyridamole-sensitive process was released by depolarization (1 mM 4-aminopyridine). Taken together, these results may qualify uridine as a neurotransmitter.

Animals↗

Acute cell damage after low Mg2+-induced epileptiform activity in organotypic hippocampal slice cultures.

Upon perfusion with Mg2+-free artificial cerebrospinal fluid (ACSF) organotypic hippocampal slice cultures develop seizure-like events and tonic recurrent discharges in which areas CA3 and CA1 and, in contrast to acute slices, also the dentate gyrus (DG) participate. Using the fluorescent dye propidium iodide (PI) we show that sustained epileptic activity causes cell death in the DG and pyramidal cell layer particularly evident in the granule cell layer of the DG. This correlates with the decrease of the electrophysiological responses to hilar stimulation. Interestingly, perfusion with carbogenated serum-free ACSF also induces some cell death which is, however, mild compared with low magnesium treated slice cultures.

Animals↗

Effects of the neuropeptides substance P, calcitonin gene-related peptide and alpha-melanocyte-stimulating hormone on the IL-8/IL-8 receptor system in a cultured human keratinocyte cell line and dermal fibroblasts.

The neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP) and alpha-melanocyte-stimulating hormone (alpha-MSH) are known to be able to regulate the production of cytokines in the skin. Since IL-8 plays an important role in cutaneous inflammation, the effects of SP, CGRP and alpha-MSH on the IL-8/IL-8 receptor (IL-8RA) systems of these cell types were studied. Cultures of human dermal fibroblasts and an immortalized keratinocyte cell line HaCaT were treated with 10-8 M SP, CGRP or alpha-MSH. The results demonstrated that these neuropeptides have different effects on the IL-8 and IL-8RA expressions of the cells. SP and CGRP upregulated the IL-8RA mRNA expression in HaCaT cells, but had no influence on their IL-8 production, whereas, alpha-MSH had no effect on either the IL-8 or the IL-8RA mRNA expression in HaCaT cells. In contrast, alpha-MSH resulted in a time-dependent induction of the IL-8 mRNA expression in dermal fibroblasts. This induction was already detectable after 6 h, and after 12 h there was a 5-fold change in comparison with the controls. The IL-8 content of the supernatant was also increased, with a maximum at 48 h after alpha-MSH treatment. The data established in the present study support the notion that neuropeptides can directly modulate the IL-8/IL-8RA system of keratinocytes and fibroblasts.

Antigens, CD↗

[Pyrimidine receptor function in the central nervous system].

A spectroscopic method, using fluorescent Ca2+, K+ and Na+ ion indicators in combination with the use of fast-kinetic techniques on the time scale of 0.00004-10 s has been applied to study mechanisms of P2 pyrimidoceptor-mediated signal transduction in brain homogenates. Effects of the known P2 receptor ligands (ATP, alpha, beta-methylene-ATP, UTP, UDP and uridine) and the P1 receptor ligand, adenosine, were compared by measuring the rates of transmembrane Ca2+, K+ and Na+ ion fluxes in resealed plasmalemma fragments and nerve endings from the rat cerebral cortex. In homogenates containing resealed plasmalemma fragments, uridine (0.03-30 microM), but not adenosine, activated two phases of Ca2+ ion influx with onsets of a few ms and hundred ms in a concentration-dependent manner. Also, the activation of the fast-phase Ca2+ ion response by ATP, UDP and alpha, beta-methylene-ATP whereas that of the slow-phase by UTP and UDP were observed with 3 microM concentration of these P2 receptor ligands. In homogenates containing resealed nerve endings, the fast-phase Ca2+ ion response to uridine was absent. UTP, but not uridine and UDP (3 microM), activated a fast K+ ion influx with onset of < 1 ms. Adenosine (3 microM) evoked a slow Na+ ion influx with onset of > 0.1 s whereas the influx of Na+ ion to uridine was detectable below 0.01 s. Both nucleotides, ATP and UTP (3 microM), activated fluctuations of transmembrane Na+ ion influx and efflux. By contrast, UDP caused efflux of Na+ ion in the subsecond range of time. Collectively these results suggest that transmembrane cation fluxes mediated by kinetically distinguishable P2U pyrimidoceptor subtypes are different.

Animals↗

Effects of barium on stimulus-induced rises in [K+]o in juvenile rat hippocampal area CA1.

Immature glia may not be able to buffer K+ ions released during neuronal activity. Therefore, we investigated entorhinal-hippocampal slices of juvenile rats (ages P15-18 and P22-26) using a perfusion medium containing 2 mM BaCl2 in order to block glial inward rectifying and leak potassium channels. In contrast to adult animals, rises in [K+]o in slices from juvenile animals elicited by repetitive alvear stimulation were not augmented by Ba2+. Ba2+ effects on fast field potentials, slow field potentials and the applied current sink source distribution were roughly similar as in adult rats. We conclude that the capacity to buffer large quantities of K+ ions by mechanisms involving Ba2+-sensitive K+ channels has not yet developed in juveniles.

Animals↗

Local mitomycin-C therapy in relapse-prevention of superficial bladder neoplasms treated by means of laser.

Authors report on local mitomycin-C (MTM-C) therapy applied subsequent to the treatment by means of Nd-YAG laser in 59 superficial (Ta-T1) bladder neoplasms. Relapse-rate in the neoplasms could be reduced by using MTM-C accompanied by minor side-effects. Seventy-two % of patients have been free from relapse for the mean 44-month follow-up period. Authors also suggest that laser therapy may favourably be completed by local chemoprophylaxis in "high-risk" type superficial bladder neoplasms.

Adult↗

[Endoscopic surgery in the management of carpal tunnel syndrome].

With the spreading of the "minimal invasive surgery" the interest was attracted in the last years in hand surgery too by the endoscopic technique. Authors describe the closed operative treatment according to Chow of the carpal tunnel syndrome. The instruments are presented and the single steps of the method was first used in detail. After exercises on cadavera the method was first used in clinical praxis by them in this country. On the basis of early experiences and the literature, the indication, the possible complications, the advantages and disadvantages of the method are analysed. According their opinion, with sufficient practice and the careful choice of indication, the endoscopic liberation of the carpal tunnel promises to be a remarkable therapeutic possibility.

Aged↗

Assessment of the efficiency of endovesical laser treatment of urinary bladder tumors on the basis of polyamine content measured in the eluent.

Authors describe a new analytical method for monitoring the treatment of vesicular tumors. Chromatographic analysis of the polyamine content of the eluent allows differential diagnostic judgement of the malignity of the laser treated tumorous tissue. The practical applicability of the method is demonstrated and evaluated on the basis of the analysis of 88 clinical cases.

Aged↗