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P Molnár

Publications and source records attributed to P Molnár.

At least 19 recordsLinked to original sources

Synaptically-released zinc inhibits N-methyl-D-aspartate receptor activation at recurrent mossy fiber synapses.

Hippocampal slices from pilocarpine-treated rats were used to explore the effect of zinc released at mossy fiber synapses on dentate granule cells. Chelation of zinc enhanced the N-methyl-D-aspartate (NMDA) receptor-mediated component of the excitatory postsynaptic current (EPSC), but did not affect the AMPA/kainate receptor-mediated component. Its effect was detectable only at negative membrane potentials and was pathway specific. Thus corelease of zinc reduces the ability of glutamate to activate postsynaptic NMDA receptors. Through this action, zinc would be expected to attenuate granule cell epileptiform activity supported by the recurrent mossy fiber pathway.

Animals↗

Biochemical basis of color as an aesthetic quality in Citrus sinensis.

The biochemical basis of color as an aesthetic quality in mature fruit of navel and Valencia orange (Citrus sinensis) was determined. Saponification of the two major color-imparting components resolved by thin-layer chromatography, followed by reversed-phase high-performance liquid chromatography, revealed that these comprised acyl esters of (9Z)-violaxanthin and beta-citraurin. Identification of the chromophores was based on cochromatography and online spectral analysis. The color quality of flavedo of mature fruit was dependent on the content and relative amounts of (9Z)-violaxanthin and beta-citraurin. Quantitative results revealed that increased color intensity was associated with a decline in the (9Z)-violaxanthin:beta-citraurin ratio from greater than 50 to below 10, an increase in flavedo (9Z)-violaxanthin and beta-citraurin content, and that measurement of the mass and ratio of these carotenoids can be used to accurately color-grade orange fruit for local and export markets.

Carotenoids↗

Carotenoid composition in the fruits of red paprika (Capsicum annuum var. lycopersiciforme rubrum) during ripening; biosynthesis of carotenoids in red paprika.

The changes in the carotenoid pigments of the Capsicum annuum var. lycopersiciforme rubrum during maturation have been investigated quantitatively by means of a HPLC technique. In all of the chromatograms, 40 peaks were detected; 34 carotenoids were identified. The total carotenoid content of the ripe fruits was about 1.3 g/100 g of dry weight, of which capsanthin constituted 37%, zeaxanthin was 8%, cucurbitaxanthin A was 7%, capsorubin constituted 3.2%, and beta-carotene accounted for 9%. The remainder was composed of capsanthin 5,6-epoxide, capsanthin 3,6-epoxide, 5,6-diepikarpoxanthin, violaxanthin, antheraxanthin, beta-cryptoxanthin, and several cis isomers and furanoid oxides. The possible biosynthetic routes for the formation of minor carotenoids containing 3,5,6-trihydroxy-beta-, 3,6-epoxy-beta-, and 6-hydroxy-gamma-end groups are described.

Capsicum↗

(9Z)-capsanthin-5,6-epoxide, a new carotenoid from the fruits of Asparagus falcatus.

From the fruits of Asparagus falcatus a novel minor (Z)-carotenoid has been isolated and, on the basis of spectral data interpretation, characterized as (9Z)-capsanthin-5,6-epoxide [(9Z,3S,5R,6S,3'S,5'R)-5,6-epoxy-3,3'-dihydroxy-5,6-dihydro-beta,kappa-caroten-6'-one, (1)]. In addition, seven other (Z)-carotenoids [namely, (9Z)-, (9'Z)-, (13Z)-, and (13'Z)-capsanthins, (9Z)- and (13Z)-capsorubins, and (9Z)-violaxanthin], which have been previously described from other plants, were isolated and identified.

Asparagus Plant↗

Lack of effect of mossy fiber-released zinc on granule cell GABA(A) receptors in the pilocarpine model of epilepsy.

The recurrent mossy fiber pathway of the dentate gyrus expands dramatically in the epileptic brain and serves as a mechanism for synchronization of granule cell epileptiform activity. It has been suggested that this pathway also promotes epileptiform activity by inhibiting GABA(A) receptor function through release of zinc. Hippocampal slices from pilocarpine-treated rats were used to evaluate this hypothesis. The rats had developed status epilepticus after pilocarpine administration, followed by robust recurrent mossy fiber growth. The ability of exogenously applied zinc to depress GABA(A) receptor function in dentate granule cells depended on removal of polyvalent anions from the superfusion medium. Under these conditions, 200 microM zinc reduced the amplitude of the current evoked by applying muscimol to the proximal portion of the granule cell dendrite (23%). It also reduced the mean amplitude (31%) and frequency (36%) of miniature inhibitory postsynaptic currents. Nevertheless, repetitive mossy fiber stimulation (10 Hz for 1 s, 100 Hz for 1 s, or 10 Hz for 5 min) at maximal intensity did not affect GABA(A) receptor-mediated currents evoked by photorelease of GABA onto the proximal portion of the dendrite, where recurrent mossy fiber synapses were located. These results could not be explained by stimulation-induced depletion of zinc from the recurrent mossy fiber boutons. Negative results were obtained even during exposure to conditions that promoted transmitter release and synchronized granule cell activity (6 mM [K(+)](o), nominally Mg(2+)-free medium, 33 degrees C). These results suggest that zinc released from the recurrent mossy fiber pathway did not reach a concentration at postsynaptic GABA(A) receptors sufficient to inhibit agonist-evoked activation.

Action Potentials↗

Gender-related physiologic differences in human neonates and the greater vulnerability of males to developmental brain disorders.

OBJECTIVE: To examine whether gender-specific physiologic differences are present at birth and can be a basis for gender-specific vulnerability to developmental disorders in males. We report on three studies of male-female physiologic and structural differences in neonates and their relevance to observed differences in the incidence of developmental disorders in males. METHODS: Study I: 56 neonates were examined for cardiac reactivity to the Moro reflex. Study II: 863 neonates' basic anthropometric data were examined to demonstrate gender-specific differences in body proportions as a possible basis for psychophysiologic differences. Study III: Developmental data on 1000 one- to 26-week-old infants were analyzed for gender-specific developmental differences in rhythmic patterns of sleeping and eating. RESULTS: Study I: There were gender-related differences in heart rate reactivity (male > female). Study II: Male newborns had significantly larger head/chest proportions, suggesting that they may have a greater metabolic demand, related to brain size. Study III: Mothers reported that infant males' sleeping rhythm developed significantly later than females', and that they slept for shorter periods at night. CONCLUSIONS: Gender-related vulnerability in brain development is proposed, based on physiologic differences during a specific early sensitive period in development. This hypothesis may help to explain the overrepresentation of males reported for most developmental disorders.

Analysis of Variance↗

gamma-Aminobutyrate, alpha-carboxy-2-nitrobenzyl ester selectively blocks inhibitory synaptic transmission in rat dentate gyrus.

gamma-Aminobutyrate, alpha-carboxy-2-nitrobenzyl ester (cGABA) is a stable photoactivatable probe used to study gamma-aminobutyrate (GABA) receptors. GABA is released from this compound when it is exposed to ultraviolet light, but little is known about the electrophysiological effects of the compound itself. Whole cell patch clamp recordings on rat hippocampal slices demonstrated that cGABA blocked polysynaptic inhibitory postsynaptic currents (IPSCs) evoked in dentate granule cells by antidromic stimulation of the mossy fibers. It also reduced monosynaptically evoked IPSCs with an IC(50) of 28 microM. In contrast, cGABA had no effect on excitatory postsynaptic currents (EPSCs) evoked by perforant path stimulation. The effect of cGABA was not mediated by depression of GABA release through activation of presynaptic GABA(B) receptors. cGABA inhibited muscimol-evoked currents by only 15% at a concentration of 40 microM. At this same concentration, it reduced the mean frequency of miniature inhibitory postsynaptic potentials by 71%, their mean peak amplitude by 44%, their mean decay time constant by 26% and the mean charge transfer per event by 52%. These effects may be explained by a phenothiazine-like modification of GABA(A) receptor kinetics and/or a selective block of somatic GABA synapses.

Animals↗

Gender-related heart rate differences in human neonates.

The aim of the present study was to examine gender-related differences in heart rate of human neonates controlled for their behavior. Previous studies could not find any difference in male and female fetuses and newborns, although this gender-dependent difference clearly exists in children and adults. The heart rate of 99 newborns (47 girls and 52 boys) was measured with simultaneous video recording of their behavior. Results proved that alert newborns showed the same difference as adults: boys had a significantly lower baseline heart rate than girls. This suggests that heart rate is gender-dependent from birth onward.

Female↗

From unidentified to 'misidentified' newborn: male bias in recognition of sex.

Our study tests in newborns the perceptual bias described in 1979 by Hildebrandt and Fitzgerald in recognizing the sex of infants, using videorecords instead of still photographs. Analysis showed a tendency for young adults to perceive newborn infants as male immediately after birth, and this perceptual bias diminished if the babies smile.

Adult↗

Recurrent mossy fiber pathway in rat dentate gyrus: synaptic currents evoked in presence and absence of seizure-induced growth.

A common feature of temporal lobe epilepsy and of animal models of epilepsy is the growth of hippocampal mossy fibers into the dentate molecular layer, where at least some of them innervate granule cells. Because the mossy fibers are axons of granule cells, the recurrent mossy fiber pathway provides monosynaptic excitatory feedback to these neurons that could facilitate seizure discharge. We used the pilocarpine model of temporal lobe epilepsy to study the synaptic responses evoked by activating this pathway. Whole cell patch-clamp recording demonstrated that antidromic stimulation of the mossy fibers evoked an excitatory postsynaptic current (EPSC) in approximately 74% of granule cells from rats that had survived >10 wk after pilocarpine-induced status epilepticus. Recurrent mossy fiber growth was demonstrated with the Timm stain in all instances. In contrast, antidromic stimulation of the mossy fibers evoked an EPSC in only 5% of granule cells studied 4-6 days after status epilepticus, before recurrent mossy fiber growth became detectable. Notably, antidromic mossy fiber stimulation also evoked an EPSC in many granule cells from control rats. Clusters of mossy fiber-like Timm staining normally were present in the inner third of the dentate molecular layer at the level of the hippocampal formation from which slices were prepared, and several considerations suggested that the recorded EPSCs depended mainly on activation of recurrent mossy fibers rather than associational fibers. In both status epilepticus and control groups, the antidromically evoked EPSC was glutamatergic and involved the activation of both AMPA/kainate and N-methyl-D-aspartate (NMDA) receptors. EPSCs recorded in granule cells from rats with recurrent mossy fiber growth differed in three respects from those recorded in control granule cells: they were much more frequently evoked, a number of them were unusually large, and the NMDA component of the response was generally much more prominent. In contrast to the antidromically evoked EPSC, the EPSC evoked by stimulation of the perforant path appeared to be unaffected by a prior episode of status epilepticus. These results support the hypothesis that recurrent mossy fiber growth and synapse formation increases the excitatory drive to dentate granule cells and thus facilitates repetitive synchronous discharge. Activation of NMDA receptors in the recurrent pathway may contribute to seizure propagation under depolarizing conditions. Mossy fiber-granule cell synapses also are present in normal rats, where they may contribute to repetitive granule cell discharge in regions of the dentate gyrus where their numbers are significant.

Animals↗

Mossy fiber-granule cell synapses in the normal and epileptic rat dentate gyrus studied with minimal laser photostimulation.

Dentate granule cells become synaptically interconnected in the hippocampus of persons with temporal lobe epilepsy, forming a recurrent mossy fiber pathway. This pathway may contribute to the development and propagation of seizures. The physiology of mossy fiber-granule cell synapses is difficult to characterize unambiguously, because electrical stimulation may activate other pathways and because there is a low probability of granule cell interconnection. These problems were addressed by the use of scanning laser photostimulation in slices of the caudal hippocampal formation. Glutamate was released from a caged precursor with highly focused ultraviolet light to evoke action potentials in a small population of granule cells. Excitatory synaptic currents were recorded in the presence of bicuculline. Minimal laser photostimulation evoked an apparently unitary excitatory postsynaptic current (EPSC) in 61% of granule cells from rats that had experienced pilocarpine-induced status epilepticus followed by recurrent mossy fiber growth. An EPSC was also evoked in 13-16% of granule cells from the control groups. EPSCs from status epilepticus and control groups had similar peak amplitudes ( approximately 30 pA), 20-80% rise times (approximately 1.2 ms), decay time constants ( approximately 10 ms), and half-widths (approximately 8 ms). The mean failure rate was high (approximately 70%) in both groups, and in both groups activation of N-methyl-D-aspartate receptors contributed a small component to the EPSC. The strong similarity between responses from the status epilepticus and control groups suggests that they resulted from activation of a similar synaptic population. No EPSC was recorded when the laser beam was focused in the dentate hilus, suggesting that indirect activation of hilar mossy cells contributed little, if at all, to these results. Recurrent mossy fiber growth increases the density of mossy fiber-granule cell synapses in the caudal dentate gyrus by perhaps sixfold, but the new synapses appear to operate very similarly to preexisting mossy fiber-granule cell synapses.

Action Potentials↗

Central core and nemaline rods in the same patient.

It is quite rare, that central cores and nemaline bodies occur in the same individual. We describe the case of a 12-year-old girl, who was born with bilateral congenital hip dislocation. Her early motor milestones were delayed. Due to proximal weakness of the lower extremities she has never been able to walk. The family history was negative. Muscle histology, histochemistry and electron microscopic studies showed a central core in nearly all muscle fibers, and nemaline rods in a few. The earlier literature and new genetical findings concerning these muscle abnormalities are also briefly summarized.

Child↗

Modelling the evolution of human trail systems.

Many human social phenomena, such as cooperation, the growth of settlements, traffic dynamics and pedestrian movement, appear to be accessible to mathematical descriptions that invoke self-organization. Here we develop a model of pedestrian motion to explore the evolution of trails in urban green spaces such as parks. Our aim is to address such questions as what the topological structures of these trail systems are, and whether optimal path systems can be predicted for urban planning. We use an 'active walker' model that takes into account pedestrian motion and orientation and the concomitant feedbacks with the surrounding environment. Such models have previously been applied to the study of complex structure formation in physical, chemical and biological systems. We find that our model is able to reproduce many of the observed large-scale spatial features of trail systems.

Behavior↗

Comparison between continuous brain tissue measurement and cerebrovenous measurement of pO2, pCO2 and pH in a porcine intracranial pressure model.

Simultaneous oxygen measurements in brain tissue (p(ti)O2) and hemoglobin saturation measurement in cerebrovenous blood in patients after severe head injury have shown different results regarding the comparability of the findings in respect to CPP and ICP. This is contrast to theoretical expectations. The aim of this study was to compare continuous ptiO2 measurement with oxygen partial pressure measurement in sagittal sinus (pO2cv) during simultaneously performance in an animal intracranial pressure model. For continuous measurement we used a newly available multisensor probe. We placed a Paratrend 7 probe (BSL, High Wycombe, UK) in the left frontoparietal white matter and measured ptiO2, pCO2 (ptiCO2) pH (pHti) and temperature (t(ti)) while simultaneously measuring these parameters (pcvO2, pcvCO2, pHcv, tcv) in the sagittal sinus in 9 pigs under general anaesthesia. A fogarty balloon catheter was placed supracerebellar infratentorial and inflated stepwise in order to increase ICP. The baseline levels of pO2ti, pCO2ti und pHti in the non-injured brain tissue showed a more extended heterogeneity compared to the findings in cerebrovenous blood. Both, pO2ti and pO2cv were significant correlated to the CPP decrease. In both measurement compartments pCO2 was inverse correlated to the course of CPP and seems the course of pH mainly to determine. p(ti)O2 as well as p(cv)O2 showed a close correlation to the CPP course and have proven to be qualified to indicate metabolic information about the relation of cerebral blood flow and metabolic cerebral demands. The measurement of CO2 tension in both measurement compartments shows a distinct heterogeneity of the absolute values and the results are only weak correlated to CPP. Metabolic influence on this parameter could not be revealed in the used experimental approach.

Animals↗

Vincamine and vincanol are potent blockers of voltage-gated Na+ channels.

The effects of three vinca derivatives on [3H]batrachotoxin binding in rat cortical synaptosomes, on the inhibition of whole-cell Na+ currents evoked in voltage-clamped cortical neurones of the rat, on the protection against veratridine-induced cell death in cortical cultures and on the maximal electroshock-induced seizures in mice were compared. Vinpocetine, vincamine and vincanol reduced [3H]batrachotoxin binding with IC50 values of 0.34, 1.9 and 10.7 microM, blocked Na+ currents with IC50 values of 44.72 and 40 microM, and protected cortical against veratridine-induced cell death with IC50 values of 0.49, 26 and 33 microM, respectively. Upon i.p. administration, vinpocetine, vincamine and vincanol attenuated maximal electric shock-induced convulsions in a dose-dependent manner with ED50 values of 27, 15.4 and 14.6 mg/kg, respectively. The present findings indicate that the three vinca derivatives are potent blockers of voltage-gated Na+ channels, a mechanism that may contribute at least in part to the pharmacological/therapeutic benefit of these drugs.

Animals↗

Differential effects of five glycine site antagonists on NMDA receptor desensitisation.

The effects of five glycine site antagonists were comparatively examined on maximal and plateau currents evoked by 200 microM N-methyl-D-aspartate (NMDA) in the presence of 1 microM glycine in cultured cerebrocortical cells of the rat using whole-cell patch-clamp technique. 5,7-Dichlorokynurenic acid, ACEA-1021 (5-nitro-6,7-dichloro-quinoxalinedione), L-695,902 (methyl 7-chloro-4-hydroxy 2(1H)-quinolone-3-carboxylate), LY-294,619 (5,7-dichloro-3-(4-hydroxphenyl)-4-hydroxyquinolin-2(1H)-one ) and RPR-104,632 (2-(3-bromo-benzyl)-6,8-dichloro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide-3-carboxylic acid) caused concentration-dependent inhibition of NMDA-activated currents. However, antagonists showed different relative efficacies to block peak currents and plateau currents, characterised by the following IC50 ratios: L-695,902: 0.98; RPR-104,632: 1.06; ACEA-1021: 1.69; LY-294,619: 1.71; and 5,7-dichlorokynurenic acid: 3.42. Our findings indicate a heterogeneity of glycine site antagonists in affecting NMDA receptor desensitisation, and suggest potential differences in their pharmacologies.

Animals↗

Thermodynamics and kinetics of t-butylbicyclophosphorothionate binding differentiate convulsant and depressant barbiturate stereoisomers acting via GABAA ionophores.

The temperature dependence of [35S]-t-butylbicyclophosphorothionate (TBPS) binding to the convulsant sites of the GABAA receptor complex was studied in membrane preparations of rat forebrain. Although specific [35S]TBPS binding was maximal around 20 degrees C, the rate constants of dissociation decreased monotonously between 37 degrees C and 2 degrees C. The displacing potencies of the convulsant S(+) enantiomer of 1-methyl-5-phenyl-5-propyl-barbituric acid (MPPB) (IC50 = 1250 +/- 30 microM) and the depressant R(-) MPPB (IC50 = 310 +/- 5 microM) did not show significant changes between 19 degrees C and 37 degrees C. Therefore barbiturate binding seems to be driven by entropic, rather than enthalpic changes. An excess of MPPB enantiomers elicited accelerated and polyphasic dissociations of [35S]TBPS as compared to the monophasic dissociation by TBPS. Arrhenius analysis was applied to the measurable initial rate constants of dissociation. Arrhenius plots were linear between 2 degrees C and 37 degrees C. Activation parameters were similar when [35S] TBPS dissociation was triggered by the convulsants TBPS and S(+) MPPB. It can be attributed to similar conformations of the closed ionophore complex. In contrast, the depressant R(-) MPPB strongly decreased the activation energy of TBPS dissociation from the open ionophore ternary complex. In whole-cell patch-clamp experiments R(-) MPPB, but not S(+) MPPB, elicited chloride currents in rat primary cortical cultures with an EC50 value of 560 +/- 30 microM and a Hill coefficient of 2.9 +/- 0.2. These currents were similar to those elicited by GABA and blocked by TBPS. A kinetic scheme is proposed for the dissociation of TBPS and to explain the different effects of MPPB enantiomers. Submillimolar R(-) MPPB is supposed to bind to (about three) barbiturate sites on GABAA-ionophores and to open them in a cooperative manner to result in a decreased activation energy for accelerated displacement of convulsant binding.

Animals↗