Biomedical subjects

L Vécsei

Publications and source records attributed to L Vécsei.

At least 37 records · Page 2Linked to original sources

PubMed2001

Functional immunohistochemistry of neuropeptides and nitric oxide synthase in the nerve fibers of the supratentorial dura mater in an experimental migraine model.

The supratentorial cerebral dura of the albino rat is equipped with a rich sensory innervation both in the connective tissue and around blood vessels, which includes nociceptive axons and their terminals; these display intense calcitonin gene-related peptide (CGRP) immunoreactivity. Stereotactic electrical stimulation of the trigeminal (Gasserian) ganglion, regarded as an experimental migraine model, caused marked increase and disintegration of club-like perivascular CGRP-immunopositive nerve endings in the dura mater and induced an apparent increase in the lengths of CGRP-immunoreactive axons. Intravenous administration of sumatriptan or eletriptan, prior to electrical stimulation, prevented disintegration of perivascular terminals and induced accumulation of CGRP in terminal and preterminal portions of peripheral sensory axons. Consequently, immunopositive terminals and varicosities increased in size; accumulation of axoplasmic organelles resulted in the "hollow" appearence of numerous varicosities. Since triptans exert their anti-migraine effect by virtue of agonist action on 5-HT(1D/B) receptors, we suggest that these drugs prevent the release of CGRP from perivascular nerve terminals in the dura mater by an action at 5-HT(1D/B) receptors. Nitroglycerine (NitroPOHL), given subcutaneously to rats, induces increased beading of nitric oxide synthase (NOS)-immunoreactive nerve fibers in the supratentorial cerebral dura mater, and an apparent increase in the number of NOS-immunoreactive nerve fibers in the dural areas supplied by the anterior and middle meningeal arteries, and the sinus sagittalis superior. Structural alterations of nitroxidergic axons innervating blood vessels of the dura mater support the idea that nitric oxide (NO) is involved in the induction of headache, a well-known side effect of coronary dilator agents.

Animals↗

PubMed2001

Sodium azide treatment decreases striatal and cortical concentrations of alpha-tocopherol in rats.

Sodium azide (20mg/kgsc), given for a maximum of 3 days to rats, significantly decreased the alpha-tocopherol concentrations in the cortex on day 2 and in the striatum on day 3. In these brain regions the oxidized glutathione values showed 30 to 36% (statistically not significant) elevation on day 3. Reduced glutathione levels were not altered. The observations suggest an important role for alpha-tocopherol in the defense against azide induced free radicals probably including NO and lipid peroxide radicals.

Animals↗

PubMed2001

The prevalence of multiple sclerosis, distribution of clinical forms of the disease and functional status of patients in Csongrád County, Hungary.

OBJECTIVE: The aim of this study was to determine the prevalence of multiple sclerosis (MS) in the population of Csongrád County, Hungary (400,128 inhabitants) and to determine the functional status (based on the Expanded Disability Status Scale; EDSS) of the patients according to the clinical forms of the disease. METHODS: The diagnosis was established with the aid of the Poser diagnostic criteria, and the degree of physical disability was determined using the Kurtzke EDSS. RESULTS: In Csongrád County, the prevalence of MS is 62/100,000. The distribution of patients according to the clinical forms of MS was as follows: 15% had the benign form, 54% had relapsing-remitting MS, 20% had secondary chronic progressive MS and 11% had the primary chronic progressive form of MS. Sixty percent of relapsing-remitting MS patients had an EDSS score of 0-4 points and 33% had an EDSS score of 4.5-6.5 points. CONCLUSION: The distribution of patients according to the clinical forms of the disease in this representative population is comparable to results in other regions of the world.

Adolescent↗

PubMed2000

CGRP and adrenomedullin receptor populations in human cerebral arteries: in vitro pharmacological and molecular investigations in different artery sizes.

The aim of the present study was to determine functional and molecular characteristics of receptors for calcitonin gene-related peptide (CGRP) and adrenomedullin in three different diameter groups of lenticulostriate arteries. Furthermore, the presence of perivascular neuronal sources of CGRP was evaluated in these arteries. In the functional studies, in vitro pharmacological experiments demonstrated that both CGRP and adrenomedullin induce alpha-CGRP-(8-37) sensitive vasodilation in artery segments of various diameters. The maximal amounts of vasodilation induced by CGRP and adrenomedullin were not different, whereas the potency of CGRP exceeded that of adrenomedullin by 2 orders of magnitude. Significant negative correlations between artery diameters and maximal responses were demonstrated for CGRP and adrenomedullin. In addition, the potency of both peptides tended to increase in decreasing artery diameter. In the molecular experiments, levels of mRNAs encoding CGRP receptors and receptor subunits were compared using reverse transcriptase polymerase chain reactions (RT-PCR). The larger the artery, the more mRNA encoding receptor activity-modifying proteins 1 and 2 (RAMP1 and RAMP2) was detected relative to the amount of mRNA encoding the calcitonin receptor-like receptor. By immunohistochemistry, perivascular CGRP containing nerve fibres were demonstrated in all the investigated artery sizes. In conclusion, both CGRP and adrenomedullin induced vasodilation via CGRP receptors in human lenticulostriate artery of various diameter. The artery responsiveness to the CGRP receptor agonists increased with smaller artery diameter, whereas the receptor-phenotype determining mRNA ratios tended to decrease. No evidence for CGRP and adrenomedullin receptor heterogeneity was present in lenticulostriate arteries of different diameters.

Adrenomedullin↗

PubMed2000

[Initial experiences with 123-Iodine-IBZM neuroreceptor scintigraphy in extrapyramidal disorders].

The receptor scintigraphy of the dopaminergic system of the brain is of interest in the evaluation of movement disorders. The 123I-IBZM is a radiopharmaceutical with affinity predominantly to postsynaptic D2 receptors. The aim of this study was to evaluate the role of IBZM SPECT investigations in the differentiation of disorders with Parkinson's syndrome. Eight patients with idiopathic Parkinson's syndrome and 8 patients Parkinson's syndrome with other etiology were investigated with 123I-IBZM SPECT (6 females, 10 males, mean age +/- SD: 59 +/- 9). The patients according to the clinical signs and symptoms, results of CT/MRI and rCBF SPECT investigation were categorized. The reconstructed SPECT slices were evaluated visually and quantitatively. The visual interpretation of the images were performed by two observer and scored the radiopharmaceutical uptake (from 1-3) of the cortex and the striatum separately. For quantification striatum/frontal cortex activity ratio were calculated with ROI technique. The differences between the patient groups were statistically analyzed by two tailed t-test. The IBZM uptake were different in the two group of patients. The striatal IBZM accumulation was higher in the idiopathic Parkinson's syndrome patients compared to the other parkinsonians. The striatum/frontal lobe activity ratio was 1.69 +/- 0.9 (mean +/- SD) in the right, 1.67 +/- 0.04 (mean +/- SD) in the left hemisphere of the patients with idiopathic Parkinson's syndrome. The corresponding data in the nonidiopathic parkinsonian group were 1.53 +/- 0.06 (mean +/- SD), 1.52 +/- 0.04 (mean +/- SD) respectively (p < 0.01). The quantitative data correlated with the results of the visual evaluation. According to the data presented IBZM-SPECT is an effective tool in the differentiation of disorders with Parkinson syndrome.

Adult↗

PubMed2000

The effects of valproate on the arachidonic acid metabolism of rat brain microvessels and of platelets.

Long-term administration of the antiepileptic drug valproate can induce hematologic, hepatic and endocrine abnormalities and morphologic alterations in the brain capillaries and glial cells. Valproate elicits bone marrow suppression, reducing the number of red blood cells and platelets, and causes platelet functional abnormalities. Various data suggest that more than one mechanism of valproate-associated toxicity may exist, but the pathomechanism of cell function alterations elicited by valproate has not yet been elucidated. The reported ex vivo experiments were designed to investigate the effects of valproate on the arachidonic acid cascade of rat brain capillaries and platelets. Valproate was administered (300 mg/kg body weight/day) in the drinking water to male Wistar rats for 2 weeks. Isolated platelets and brain microvessels were labelled with [14C]arachidonic acid and the released [14C]eicosanoids were separated by overpressure thin-layer chromatography and determined quantitatively by liquid scintillation counting. Valproate treatment reduced the synthesis of cyclooxygenase and lipoxygenase products in rat platelets. In brain microvessels valproate stimulated the synthesis of lipoxygenase metabolites and attenuated the cyclooxygenase pathway. Modifications of the arachidonate cascade in platelets and brain microvessels may contribute to the cell function alterations caused by valproate.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed2000

Diminished blood levels of reduced glutathione and alpha-tocopherol in two triosephosphate isomerase-deficient brothers.

The glutathione redox system and alpha-tocopherol, both of which are essential for maintaining the normal structure of biological membranes, some other lipid-soluble antioxidants (lycopene, beta-carotene, retinol), and lipid peroxidation, were investigated in the blood from two triosephosphate isomerase (TPI)-deficient brothers. Both of the genetically identical compound heterozygote brothers have congenital hemolytic anemia, but only one of them has a neurological defect, the second cardinal symptom of TPI deficiency. Whole blood reduced glutathione levels were markedly decreased in both brothers. The glutathione reductase activities as well as the NADPH contents of their erythrocytes were in the normal range or slightly enhanced. Increased ratio of oxidized/reduced glutathione, elevated glutathione S-transferase activity, and increased d-lactate level, a metabolite of the glyoxalase pathway, were detected only in the neurologically affected propositus. The plasma carotenoids (lycopene + beta-carotene), alpha-tocopherol/cholesterol + triglyceride ratios, and the erythrocyte alpha-tocopherol levels were significantly decreased in both patients. It seems conceivable that membrane alterations due to the low level of these reducing agents may contribute to the shortened life span of erythrocytes. The imbalance of the prooxidant/antioxidant homeostasis as well as the increased rate of methylglyoxal formation may also have been involved in the development of the neurological manifestations in the propositus.

Adult↗

PubMed2000

P300 component of visual event-related potentials distinguishes patients with idiopathic parkinson's disease from patients with essential tremor.

A considerable rate of misdiagnosis has recently been reported in movement disorders. One of the most difficult clinical problems is the differentiation of Parkinson's disease and essential tremor. In this study, we have examined whether event-related potentials (ERPs) could aid in the solution of this differential diagnostic problem. Visual ERPs were obtained by using an "oddball" paradigm in 20 patients with idiopathic Parkinson's disease (IPD), 20 patients with essential tremor (ET), and 20 age-matched control subjects. We found that the P300 amplitudes were selectively reduced in the IPD group at the midline (Fz, Cz, Pz) electrode sites, whereas the ET group exhibited selectively elevated P300 amplitudes at the left parietal and frontal (F3, P3) recording sites. The patients with IPD, but not ET, showed a significant prolongation of the P300 latency at each electrode site. Similarly, only the IPD patients were significantly slower in responding to the target stimulus. The primary visual evoked potential (P100) did not distinguish among the IPD, ET, and control subjects. These results suggest that visual ERPs might provide a useful diagnostic method for differentiating IPD from ET.

Aged↗

PubMed2000

Effects of eletriptan on the peptidergic innervation of the cerebral dura mater and trigeminal ganglion, and on the expression of c-fos and c-jun in the trigeminal complex of the rat in an experimental migraine model.

Nociceptive axons and terminals in the supratentorial cerebral dura mater display an intense calcitonin gene-related peptide (CGRP) immunoreactivity. In an experimental migraine model, it has been shown that electrical stimulation of the rat trigeminal ganglion induced an increase in the lengths of CGRP-immunoreactive axons, increased size and number of pleomorphic axonal varicosities in the dura mater, and an increased number of c-jun and c-fos protein-expressing nerve cells in the trigeminal complex. We demonstrate the effect of the highly specific and moderately lipophilic serotonin agonist eletriptan (Pfizer) which prevents the effects of electrical stimulation in the dura mater. Eletriptan also affected the caudal trigeminal complex; it markedly reduced the numbers of the oncoprotein-expressing cells, mainly after stimulation and to some extent also in nonstimulated animals. Eletriptan also affected expression of CGRP in perikarya of trigeminal ganglion cells, insofar as the number of small nerve cells exhibiting a compact CGRP immunoreaction was decreased to one quarter of the original value. In all these respects, eletriptan acted in a similar way to sumatriptan, with the notable exception that eletriptan also blocked the stimulation-induced effects in the nucleus caudalis trigemini and the upper cervical spinal cord (trigeminal complex), whereas sumatriptan did not. It is concluded that eletriptan, acting on perikarya and both the peripheral and the central axon terminals of primary sensory neurons, exerts its antimigraine effect by an agonist action on 5-HT1B/1D receptors throughout the entire trigeminal system, probably by passing the blood-brain-barrier because of its lipophilic character.

Animals↗

PubMed2000

Platelet arachidonate cascade of migraineurs in the interictal phase.

Morphological and functional alterations of platelets in migraineurs may be linked to the development of migraine. We examined the eicosanoid synthesis of platelets of untreated female migraineurs in a headache-free period and compared it to that of age- and blood group-matched healthy female volunteers. In the platelets of headache-free migraineurs significantly less amounts of anti-aggregatory prostaglandin D2 and prostacyclin, as well as of 12-L-hydroxy-5,8,10-heptadecatrienoic acid (a potent endogenous inducer of endothelial prostacyclin production) were produced, while the synthesis of platelet aggregatory thromboxane did not differ when compared to that of healthy women. These results suggest that the platelet eicosanoids of migraineurs in the headache-free period might promote the development of cellular, vascular and neurological events inducing headache.

Adult↗

PubMed1999

[Treatment of relapsing-remitting multiple sclerosis with interferon beta type 1-b].

Interferon-beta-1b was the first drug found to slow the progression of relapsing-remitting multiple sclerosis, with a reported decrease in the relapse rate of up to 34%. The present study involved 35 patients treated with interferon-beta-1b for one year. The aims of the study were: a) to compare the changes in the relapse rate and the number of days of hospitalization with other data, b) to compare the steroid needs required to treat relapses for one year before and in the year of interferon-beta-1b treatment. Our data indicated that the relapse rate may decrease as much as 77% following the introduction of interferon-beta-1b treatment. The adverse effects and the changes in the EDSS grades were similar to the published data. The duration of hospitalization decreased by 84% and the amount of methylprednisolone needed for remission by 78%. This data suggest that the impairment of the condition of the patients may be delayed considerably, while some of them can continue to work for a longer period, the standard of life of these patients therefore being more tolerable.

Humans↗

PubMed1999

Effect of a nitric oxide donor on nitroxergic nerve fibers in the rat dura mater.

Nitroglycerine, given subcutaneously to rats (10 mg/kg body weight) induces increased beading of nitric oxide synthase immunoreactive (NOS-IR) nerve fibers in the supratentorial cerebral dura mater, and an apparent increase in the number of NOS-IR nerve fibers in the dural areas supplied by the anterior and middle meningeal arteries, and the sinus sagittalis superior. Structural alterations of nitroxergic axons innervating blood vessels of the dura mater support the idea that nitric oxide is involved in the induction of headache also by a primary peripheral action, a well-known side effect of coronary dilator agents.

Animals↗

PubMed1999

Nonenzymatic antioxidants of blood in multiple sclerosis.

Free radical action has been suggested as a causal factor in multiple sclerosis. We investigated the plasma level of lipid peroxides expressed in terms of malone dialdehyde and changes in blood nonenzymatic antioxidants (glutathione, alpha-tocopherol, retinol, plasma sulfhydryl groups, and uric acid) in multiple sclerosis patients with exacerbation or in remission, including a group treated with beta-interferon. The malone dialdehyde level was increased by 38% (n.s.) during exacerbations. The blood concentration of oxidized glutathione was likewise elevated (P<0.05), while the ratio of plasma alpha-tocopherol to cholesterol plus triglyceride was decreased (P<0.001). These changes suggest increased free radical production and consumption of the scavenger molecules during the active phase of the disease. Blood reduced glutathione level was increased (P<0.01) during exacerbation and remission as well. The rise in this thiol is likely to be a compensatory mechanism defending the cells from further oxidant injuries. Beta-interferon increased plasma alpha-tocopherol levels (P<0.001) but not the lipid corrected alpha-tocopherol value. Other parameters were not influenced by the drug.

Adult↗

PubMed1999

Effects of in vivo sodium azide administration on the immunohistochemical localization of kynurenine aminotransferase in the rat brain.

Endogenous excitotoxins that act on receptors of cerebral excitatory amino acids play important roles in the pathogenesis of excitotoxic brain diseases. Activation of excitatory amino acid receptors results in neuronal death characteristic of these disorders. Kynurenic acid, a powerful endogenous excitatory amino acid receptor antagonist, which is therefore widely regarded as a potent neuroprotective agent, is produced from its biological precursor, L-kynurenine, by the action of the enzyme kynurenine aminotransferase-I. The chemical hypoxia induced by mitochondrial toxins produces a secondary excitotoxicity, leading to the activation of N-methyl-D-aspartate receptors. Accordingly, sodium azide, an inhibitor of cytochrome oxidase, induces the release of excitotoxins via an energy impairment and this, in turn, results in neurodegeneration. Since energy-dependent secondary excitotoxic mechanisms also account for the pathogenesis of neurodegenerative diseases, a study was made of the effects of sodium azide on the immunohistochemical localization of kynurenine aminotransferase-I. After in vivo administration of sodium azide for five days, a markedly decreased glial kynurenine aminotransferase-I immunoreactivity was found by immunohistochemical techniques in the glial cells of the striatum, hippocampus, dentate gyrus and temporal cortex; at the same time, kynurenine aminotransferase-I started to be expressed by nerve cells which had not been immunoreactive previously. The accumulation of kynurenine aminotransferase-I reaction product around the ribosomes of neuronal endoplasmic reticulum suggests de novo synthesis of kynurenine aminotransferase-I in the reactive nerve cells.

Animals↗

PubMed1999

Amino acids in the saliva of patients with migraine.

There are a number of hypotheses concerning the pathogenesis of migraine, but they are frequently conflicting. In addition to the vascular hypothesis, clinical data are available that excitatory amino acids may play an important role in the development of the disease. In this study, free amino acid concentrations were measured by RP-HPLC in the saliva of 23 migraineurs without aura, 14 migraineurs with aura, and 20 healthy subjects. Significantly higher concentrations of glutamic acid, serine, glycine, arginine, and tyrosine were found in the saliva samples of both groups of migraineurs relative to the control group. It is suggested that amino acids causing hyperexcitability in the central nervous system may be linked to the pathogenesis of migraine.

Adult↗

PubMed1999

Valproate treatment and platelet function: the role of arachidonate metabolites.

PURPOSE: Valproate (VPA) is an extensively used drug in the therapy of epilepsies. One of the most frequently reported side effects of VPA is hemorrhagic diathesis. Some authors emphasized the decreased platelet count as the basis of VPA-induced hemorrhagic diathesis, but some reports suggested that a significant proportion of patients with normal platelet count may still have an altered platelet function. The mechanism of the VPA-induced platelet dysfunction has not yet been elucidated. A determining element of platelet functions is the arachidonate cascade. Present ex vivo experiments were designed to determine whether a relation exists between the incidence of hemostasis caused by VPA and the effect of this drug on the arachidonate cascade of platelets. METHODS: Platelets were isolated from patients receiving long-term VPA treatment (serum level, 36.04+/-16.12 microg/ml; n = 10) or carbamazepine (CBZ) treatment (serum level, 5.24+/-2.67 microg/ml; n = 10) and were labeled with [14C]arachidonic acid. (CBZ-treated patients were chosen as a control group, because CBZ causes blood dyscrasias similar to those elicited by VPA, but there has been no report that CBZ induces a platelet dysfunction.) The 14C-eicosanoids were separated by means of overpressure thin-layer chromatography and determined quantitatively by liquid scintillation. RESULTS: Even when the mean plasma concentration of the drug was low, VPA treatment reduced the activity of the arachidonate cascade in platelets. VPA effectively inhibited the cyclooxygenase pathway and the synthesis of the strong platelet aggregator thromboxane A2. CONCLUSIONS: Inhibition of the platelet arachidonate cascade may contribute to the platelet-function alterations caused by VPA.

Adult↗

PubMed1999

Wernicke's encephalopathy induced by hyperemesis gravidarum.

A report is presented on a patient with Wernicke's encephalopathy secondary to hyperemesis gravidarum. The 25-year-old female presented 11 weeks into pregnancy with prolonged vomiting. Neurological examination 8 weeks later demonstrated obtunded sensations, nystagmus and ataxia of gait. MR imaging revealed bilateral lesions in the mediodorsal nuclei of thalami, in the hypothalamus and in the periaqueductal gray matter (1). The neurological signs and the MRI findings pointed to a diagnosis of Wernicke's encephalopathy. The patient was treated with intramuscular vitamin B1 followed by oral thiamine until the end of pregnancy. The subsequent course of the pregnancy was uncomplicated, and resulted in the delivery of a healthy 2970 g male infant. A review of the literature published during the last 30 years revealed an additional 20 cases of Wernicke's encephalopathy induced by hyperemesis gravidarum. Only half of these pregnancies resulted in the birth of a normal infant.

Adult↗

PubMed1999

Analysis of CAG repeat expansion in Huntington's disease gene (IT 15) in a Hungarian population.

Huntington's disease (HD) is a neurodegenerative disorder with autosomal dominant inheritance. The genetic defect is a CAG trinucleotide repeat expansion at the 5' end of the IT 15 gene on chromosome 4. This gene has not been analyzed in the Hungarian population yet. To obtain data DNA from 26 HD patients, 18 members of their families and 70 normal controls was amplified in the involved region by polymerase chain reaction. The CAG repeat numbers varied from 37 to 70 (median: 43) in HD patients and asymptomatic carriers, while individuals of the normal control group had 10-36 CAG repeat numbers (median: 18). The length of CAG repeat expansion in Hungarian HD patients was similar to that reported from other countries. The group of normal controls had the same CAG repeat expansion as populations reported from Western European countries. It is a useful piece of data for population genetics to prove that the population of Hungary is a mélange of different nations that influenced the history of the country in the last 11 centuries. As opposed to this, the only closely related nation, the Finnish, was genetically more isolated during this time, so the frequency of HD (and also the number of CAG repeats in normal individuals) proved to be exceptionally low.

Adult↗