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Biomedical subjects

B Gulyás

Publications and source records attributed to B Gulyás.

At least 19 recordsLinked to original sources
PubMed2006

Nitric oxide production in striatum and pallidum of cirrhotic rats.

Ammonium and manganese are neurotoxic agents related to brain metabolic disturbances observed after prolonged liver damage. The aim of this study was to assess the production of nitric oxide (NO) in the brain of cirrhotic rats exposed to manganese. We induced cirrhosis by bile duct ligation for 4 weeks in rats. From brain, striatum and globus pallidus were dissected out, and NO synthase activity and the content of nitrites plus nitrates (NOx) were determined. In pallidum we found a diminished constitutive NO synthase activity from cirrhotic rats, independently of manganese exposure. This result was confirmed by low levels of NOx in the same brain area (P<0.05, two-way ANOVA). This finding was not related to protein expression of NO synthase since no differences were observed in immunoblot signals between cirrhotic and sham-operated animals. Results from present study suggest that the production of NO is reduced in basal ganglia during cirrhosis.

Animals↗
PubMed2004

Limbic reductions of 5-HT1A receptor binding in human temporal lobe epilepsy.

OBJECTIVE: To test the hypothesis that in mesial temporal lobe epilepsy (MTLE) there is involvement outside of mesial structures and that this involvement affects serotonin systems, thus suggesting a mechanism for affective symptoms in this population. METHODS: Serotonin 5-HT1A receptor binding was studied with PET and [Carbonyl-11C]WAY-100 635 in 14 patients (6 with left-, 8 with right-sided mesial temporal lobe focus) and 14 controls. The 5-HT1A receptor binding potential was calculated for hippocampus, amygdala, orbitofrontal, insular, lateral temporal, and anterior cingulate cortex, in raphe nuclei, and in two regions presumably uninvolved in the epileptogenic process (parietal, and dorsolateral frontal neocortex). RESULTS: The binding potential was reduced in the epileptogenic hippocampus (p = 0.0001) and amygdala (p = 0.0001) in all patients, including the six with normal [18F]FDG PET and MRI. It was also reduced in the anterior cingulate (p = 0.002), insular (p = 0.015), and lateral temporal cortex (p = 0.029) ipsilaterally to the focus, in contralateral hippocampus (p = 0.025), and in the raphe nuclei (p = 0.016). CONCLUSION: Patients with severe MTLE show reduced 5-HT1A receptor binding potential in the EEG-focus, and its limbic connections. [(11)C]WAY-100 635 PET may provide additional information to EEG, [18F]FDG PET, and MRI when evaluating patients with intractable seizures. Reductions in 5-HT1A binding in the insula and cingulate suggest a mechanism by which affective symptoms in MTLE may result.

Adult↗
PubMed2002

PET studies on the brain uptake and regional distribution of [11C]vinpocetine in human subjects.

OBJECTIVES: Vinpocetine is a compound widely used in the prevention and treatment of cerebrovascular diseases. It is still not clear whether the drug has a direct and specific effect on neurotransmission or its effects are due to extracerebral actions, such as changes in cerebral blood flow. The main objective of the present investigation was to determine the global uptake and regional distribution of radiolabelled vinpocetine in the human brain in order to explore whether it may have direct central nervous system effects. MATERIAL AND METHODS: Three healthy subjects were examined with positron emission tomography and [11C]vinpocetine. The regional uptake was determined in anatomically defined volumes-of-interest. The fractions of [11C]vinpocetine and labelled metabolites in plasma were determined using high pressure liquid chromatography. RESULTS: The uptake of [11C]vinpocetine in brain was rapid and 3.7% (mean; n = 4) of the total radioactivity injected was in brain 2 min after radioligand administration. The uptake was heterogeneously distributed among brain regions. When compared with the cerebellum, an a priori reference region, the highest regional uptake was in the thalamus, upper brain stem, striatum and cortex. Following an initial peak, the total concentration of radioactivity in blood was relatively stable with time, whereas the concentration of the unchanged compound decreased with time in an exponential manner. CONCLUSION: Vinpocetine, administered intravenously in humans, readily passes the blood-brain barrier and enters the brain. Its regional uptake and distribution in the brain is heterogeneous, indicating binding to specific sites. The brain regions showing increased uptake in the human brain correspond to those in which vinpocetine has been shown to induce elevated metabolism and blood flow. These observations support the hypothesis that vinpocetine has direct neuronal actions in the human brain.

Adult↗
PubMed2002

Autoradiographic evaluation of [11C]vinpocetine binding in the human postmortem brain.

The main objective ofthe study was to evaluate with autoradiographic technique whether or not [11C]vinpocetine, a compound widely used in the prevention and treatment of cerebrovascular diseases (Cavinton, Gedeon Richter Ltd., Budapest), binds to specific sites in the human brain in post mortem human brain sections. Binding was assessed under four conditions: the incubation was performed using Tris-HCl buffer with or without the addition of salts (0.1% (weight/vol) ascorbic acid, 120 mM NaCl, 5 mM KCl, 2 mM CaCl2 and 1 mM MgCl2), with or without the addition of excess (10 microM) unlabelled vinpocetine. Measurements on digitized autoradiograms indicated that [11C]vinpocetine labelled all grey matter areas in the human brain to a similar extent and no significantly heterogeneous binding could be demonstrated among cortical or subcortical regions. The addition of excess unlabelled vinpocetine lowered the binding slightly in all regions. Although these results indicate that [11C]vinpocetine does not bind to human brain transmitter receptors or transporters with a high affinity (Ki < 10 nM), it cannot be ruled out that the compound binds to receptors and/or transporters with lower affinity.

Autoradiography↗
PubMed2001

[The effect of a single-dose intravenous vinpocetine on brain metabolism in patients with ischemic stroke].

The effect of a single-dose i.v. infusion of vinpocetine on the cerebral blood flow (CBF) and glucose metabolism of post-stroke patients was studied by measuring the regional and global cerebral metabolic rates of glucose (CMRglu) and the corresponding kinetic constants before and after treatment. Transcranial Doppler (TCD) and single photon emission tomography (SPECT) measurements were also performed. The cerebral glucose metabolism was significantly higher in the contralateral hemisphere than in the affected one before therapy. In the affected hemisphere the regional glucose metabolism was inhomogenous: relatively low values were measured in the stroke region, whereas it was increased in the peristroke region. Although a single-dose vinpocetine treatment did not affect significantly the regional or global metabolic rates of glucose, the glucose transport (both intracellular up-take and release) was strongly affected in the whole brain, in the contralateral hemisphere and in the peri-infarct area of the symptomatic hemisphere. A slightly increased (not significant, N. S.) cerebral blood flow could be observed in the contralateral and a decreased flow (N. S.) in the symptomatic hemisphere.

Aged↗
PubMed2001

An overview on functional receptor autoradiography using [35S]GTPgammaS.

[35S]GTPgammaS binding autoradiography is a novel method to study the distribution and function of neurotransmitter receptors in tissue sections. This technique unifies the advantages of receptor-autoradiography and [35S]GTPgammaS binding, providing anatomical and functional information at the same time. Due to these two main features, it can also be called 'functional autoradiography'. [35S]GTPgammaS binding has long been used to study the first step of the intracellular signaling pathway, but until the mid 1990s it has only been performed on cell membrane extracts. Functional autoradiography evolved from this biochemical assay and ligand autoradiography, and is based on the increase in guanine nucleotide exchange at G-proteins upon agonist stimulation. With the technique, activation of G-protein-coupled receptors upon agonist binding can be detected, and, at the same time, the location of activated receptors can also be visualized. Thus only those presumably active G-protein-coupled receptors are visualized that can be involved in signal transduction. In the past 5 years the technique has become more and more frequently used in neuroscience, and it has been adapted to several receptors in different species, including also the human brain. [35S]GTPgammaS binding autoradiography can be used to describe the distribution of G-protein-coupled receptors. Some inferences on their coupling efficiency can also be drawn. Besides the localization of ligand binding sites, it provides information on the action of the ligand on the receptor: agonists, antagonists, and inverse agonists can clearly be distinguished. Moreover, [35S]GTPgammaS binding autoradiography can successfully be combined with other in vitro assays, like receptor autoradiography, in situ hybridization histochemistry, or even with biochemical and electrophysiological experiments. This review presents an overview on the history and the development of this technique. Its main advantages and limitations are summarized, together with a few basic technical questions. A number of experiments performed with [35S]GTPgammaS binding autoradiography so far, and some possible applications for the future, are also reviewed.

Animals↗
PubMed2001

Neural networks for internal reading and visual imagery of reading: a PET study.

Regional cerebral blood flow (rCBF) measurements with positron emission tomography (PET) were made on 10 volunteers in rest condition as well as while the subjects, with closed eyes, (i) internally listed the letters of the alphabet and cited the first verse of the Hungarian national anthem, (ii) visualised the capital letters of the alphabet, and (iii) visualised the capital letters of the first verse of the Hungarian national anthem. Significant changes in rCBF indicated various networks of cortical neuronal populations active during the tasks. Internal listing, as compared to the rest condition, activated the left precentral gyrus. Visualising the letters of the alphabet, when compared to the rest condition, activated a cortical network comprising fields along the banks of the left and right intraparietal sulci, the left medial frontal, precentral and occipital sulci, and the right superior frontal gyrus. Visualising the letters of the anthem, when compared to the rest condition, activated a cortical network comprising fields along the banks of the left and right intraparietal sulci, the left medial and inferior frontal gyri, and the right anterior cingulate gyrus. Contrasting the two visualisation tasks revealed task specific activation in the left lateral occipital gyrus (alphabet vs. anthem visualisation) and in the left anterior cingulate gyrus (anthem vs. alphabet visualisation). The data indicate that visual imagery of letters of the alphabet or a text engages a widespread network of cortical fields in the visual association cortices and the frontal cortex, without the engagement of the primary (V1) and secondary (V2) visual cortical areas. This finding supports the hypothesis that neuronal populations engaged by visual imagery and visual perception only partially overlap. The networks, activated in the visualisation tasks, have a core which is identical in the different visualisation tasks. The core network is complemented in a task-specific manner by the recruitment of additional cortical neuronal populations.

Adult↗
PubMed2001

PET studies with carbon-11 radioligands in neuropsychopharmacological drug development.

A basic problem in the discovery and development of novel drugs to be used in the treatment of neurological and psychiatric disorders is the absence of relevant in vitro or in vivo animal models that can yield results which can be extrapolated to man. Drug research now benefits from the fast development of functional imaging techniques such as positron emission tomography (PET) which trace radiolabelled molecules directly in the human brain. PET uses molecules that are labelled with short-lived radionuclides and injected intravenously into experimental animals, human volunteers or patients. The most frequent approach is to study how an unlabelled drug inhibits specific binding of a well characterised selective PET radioligand. The alternative direct approach is to radiolabel a new potential drug and to trace its uptake, anatomical distribution and binding in brain. Furthermore, the effects of a novel drug on physiological-biochemical parameters, such as glucose metabolism or blood flow, can also be assessed. The demonstration of quantitative relationships between drug binding in vivo and drug effects in patients is used to validate targets for drug action, to correlate pharmacological and physiological effects, and to optimise clinical treatment.

Animals↗
PubMed2001

Brain radioligands--state of the art and new trends.

Non-invasive radioligand imaging methods for brain receptor studies use either short-lived positron-emitting radionuclides such as 11C and 18F for positron emission tomography (PET) or single photon-emitting radionuclides such as 123I for single photon emission computed tomography (SPECT). PET and SPECT use radioligands which are injected intravenously into experimental animals, human volunteers or patients. The main applications of radioligands in brain research concern human neuropsychopharmacology and the discovery and development of novel drugs to be used in thetherapy of neurological and psychiatric disorders. A basic problem in PET and SPECT brain receptor studies is the lack of useful radioligands with appropriate binding characteristics. Prerequisite criteria need to be satisfied for a radioligand to reveal target binding sites in vivo. This section will discuss these important criteria and also review recent examples in neuroreceptor radioligand development such as selective radioligands for brain monoamine transporters.

Animals↗
PubMed2000

Cerebral blood flow and glucose metabolism in mitochondrial disorders.

OBJECTIVE: To investigate cerebral metabolism by 2-[18F]fluorodeoxy-d-glucose (FDG) uptake using PET and cerebrovascular reverse capacity by transcranial Doppler sonography (TCD) in different mitochondrial diseases (mitochondrial myopathy; mitochondrial encephalopathy, lactacidosis, and stroke-like episodes [MELAS]; and chronic external ophthalmoplegia). BACKGROUND: Previous studies on individual patients with mitochondriopathies revealed abnormal accumulations of mitochondria in endothelium, smooth muscle cells, and pericytes of blood vessels in different parts of the nervous system (cerebrum, cerebellum, sural nerve) and skeletal muscle. On this basis, some investigators suggested a pathogenic role of vascular involvement in the MELAS syndrome and other encephalopathies. smhd1 DESIGN/METHODS: The authors investigated neuronal metabolism and cerebrovascular involvement with PET in 5 cases and with TCD with acetazolamide stimulation in 15 cases. The patients were divided into three groups: 1) interictal MELAS (n = 4); 2) progressive external ophthalmoplegia (n = 6); and 3) pure mitochondrial myopathy and neuropathy (n = 5). The results were compared with those from matched normal control subjects. The diagnoses were based on clinical phenotype as well as histopathologic and molecular analysis. RESULTS: Cerebral glucose uptake was impaired in all patients, both with and without CNS symptoms, particularly in the occipital and temporal lobes. The vasoreactivity of the small arterioles to acetazolamide did not differ significantly between the patients and healthy control subjects or between the different groups of mitochondrial disorders. CONCLUSIONS: MELAS does not appear to be a functional disturbance of arterioles leading to an ischemic vascular event. The clinical symptoms in MELAS are not the result of a mitochondrial angiopathy but are the consequences of a mitochondrial cytopathy affecting neurons or glia. There is no correlation between the decreased glucose metabolism and the duration of the disease.

Acetazolamide↗
PubMed2000

Role of sodium channel inhibition in neuroprotection: effect of vinpocetine.

Vinpocetine (ethyl apovincaminate) discovered during the late 1960s has successfully been used in the treatment of central nervous system disorders of cerebrovascular origin for decades. The increase in the regional cerebral blood flow in response to vinpocetine administration is well established and strengthened by new diagnostical techniques (transcranial Doppler, near infrared spectroscopy, positron emission tomography). The latest in vitro studies have revealed the effect of the compound on Ca(2+)/calmodulin dependent cyclic guanosine monophosphate-phosphodiesterase 1, voltage-operated Ca(2+) channels, glutamate receptors and voltage dependent Na(+)-channels; the latest being especially relevant to the neuroprotective action of vinpocetine. The good brain penetration profile and heterogenous brain distribution pattern (mainly in the thalamus, basal ganglia and visual cortex) of labelled vinpocetin were demonstrated by positron emission tomography in primates and man. Multicentric, randomized, placebo-controlled clinical studies proved the efficacy of orally administered vinpocetin in patients with organic psychosyndrome. Recently positron emission tomography studies have proved that vinpocetine is able to redistribute regional cerebral blood flow and enhance glucose supply of brain tissue in ischemic post-stroke patients.

Animals↗
PubMed2000

Visual exploration of form and position with identical stimuli: functional anatomy with PET.

Visual form and position perception in primates is thought to engage two different sets of cortical visual areas. However, the original concept of two functionally different and anatomically segregated pathways has been challenged by recent investigations. Using identical stimuli in the centre of the visual field with no external cues, we examined whether discrimination of form aspects and position aspects would indeed activate occipito-temporal and occipito-parietal areas, respectively. We measured and localised regional cerebral blood flow (rCBF) changes in the brain with positron emission tomography (PET) and 15O-butanol while the subjects performed four visual tasks: position discrimination (PD), form discrimination (FD), joint form and position discrimination (FPD), and a control task. Discrimination of form contrasted with discrimination of position resulted in rCBF increases in the lateral occipital and fusiform gyri. Discrimination of position contrasted with discrimination of form yielded rCBF increases in the left frontal eye field and middle frontal gyrus. No extra activations were seen when the joint form and position discrimination task was contrasted with either the individual form and position discrimination tasks. When the individual form and position discrimination tasks were contrasted with the control task, form discrimination resulted in activations in both occipito-temporal and occipito-parietal visual cortical regions, as well as in the right middle-frontal gyrus. Position discrimination resulted in activation in occipito-parietal visual cortical regions, the left frontal eye field and the left middle frontal gyrus. These findings are consistent with the view that the processing of visual position information activates occipito-parietal visual regions. On the other hand, the processing of 2D visual form information, in addition to the activation of occipito-temporal neuronal populations, also involves the parietal cortex. Form and position discrimination activated different nonsymmetrical prefrontal fields. Although the visual stimuli were identical, the network of activated cortical fields depended on whether the task was a form discrimination task or a position discrimination task, indicating a strong task dependence of cortical networks underlying form and position discrimination in the human brain. In contrast to former studies, however, these task-dependent macronetworks are overlapping in the posterior parietal cortex, but differentially engage the occipito-temporal and the prefrontal cortex.

Adult↗
PubMed1999

[Autoradiography of neurotransmitter receptors in whole human brain hemisphere sections].

Autoradiography is one of our most important tools to gain knowledge about neurotransmitter-receptors playing a key-role in information transmission between neurons. Autoradiography, in its most sophisticated form, is performed on whole human hemispheric sections. The main objective of the authors is to present this application of autoradiography. This in vitro method produces images with high spatial resolution that enable us to qualitatively and quantitatively characterize the regional distribution of the receptors under study. With this technique both the different receptor systems in various physiological and pathological conditions of the brain and the pharmacological parameters of the radioligand, itself, used for a given investigation can be analysed. As a consequence, the results of autoradiography can be successfully used in drug development and trial, brain research and, indirectly, in the every day practice of physicians (diagnosis, differentialdiagnosis, therapy). Autoradiography plays an important role in the validation of in vivo techniques (positron emission tomography, single photon emission tomography) and results in a more complex (in vivo and in vitro) insight into the neurochemical organisation of the brain.

Autoradiography↗
PubMed1999

[Cerebral uptake and metabolism of (11C) Vinpocetine in monkeys: PET studies].

Vinpocetine, a vinca alkaloid, is a therapeutic agent widely used in the treatment of acute and chronic stroke patients. To explore the uptake and distribution of vinpocetine in the primate brain, vinpocetine was labelled with 11C and positron emission tomography (PET) was used to measure the uptake and distribution of 11C-vinpocetine in the brain and the trunk of a cynomolgous monkey. HPLC was used to determine the concentration of vinpocetine and its labelled metabolites in blood and plasma. Following the radioligand's intravenous administration, after an initial peak, the total concentration of radioactivity in blood was relatively stable with time. The uptake of 11C-vinpocetine into the brain was rapid and about 5% of the total injected radioactivity was present in the brain two minutes after drug administration. These facts indicate that the compound passes the blood-brain barrier readily and enters the brain. The radioactivity uptake was heterogeneously distributed among brain regions. The highest concentrations were found in the thalamus, the basal ganglia and certain neocortical regions. In an earlier PET investigation on chronic stroke patients the highest increases in cerebral blood flow and glucose metabolism after intravenous vinpocetine treatment occurred in these anatomical structures. The heterogenous regional distribution of vinpocetine and the observation that the highest uptake values in brain structures go parallel with the greatest regional blood flow and glucose metabolic rate increases indicate that direct CNS effects of vinpocetine should be considered as an explanation for the therapeutic effects. The confirmation of this suggestion requires further investigations.

Animals↗
PubMed1999

Neuronal correlates of real and illusory contour perception: functional anatomy with PET.

Illusory contours provide a striking example of the visual system's ability to extract a meaningful representation of the surroundings from fragmented visual stimuli. Psychophysical and neurophysiological data suggest that illusory contours are processed in early visual cortical areas, and neuroimaging studies in humans have shown that Kanizsa-type illusory contours activate early retinotopic visual areas that are also activated by real contours. It is not known whether other types of illusory contours are processed by the same mechanisms, nor is it clear to what extent attentional effects may have influenced these results, as no attempt was made to match the salience of real and illusory stimuli in previous imaging studies. It therefore remains an open question whether there are any brain regions specifically involved in the perception of illusory contours. To address these questions, we have used 15O-butanol positron emission tomography (PET) and a novel kind of illusory contour stimulus that is induced only by aligned line ends. By employing a form discrimination task that was matched for attention and stimulus salience across conditions we were able to directly contrast perception of real and illusory contours. We found that the regions activated by illusory contour perception were the same as those activated by real contours. Only one region, located in the right fusiform gyrus, was significantly more strongly activated by perception of illusory contours than by real contours. In addition, a principal component analysis suggested that illusory contour perception is associated with a change in the correlation between V1 and V2. We conclude that different kinds of illusory contours are processed by the same cortical regions and that these regions overlap extensively with those involved in processing of real contours. At the regional level, perception of illusory contours thus appears to differ from perception of real contours by the degree of involvement of higher visual areas as well as by the nature of interaction between early visual areas.

Adult↗