23 results on '"Klivényi, Péter"'
Search Results
2. Real-world operation of multiple sclerosis centres in Central-Eastern European countries covering 107 million inhabitants
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Kokas, Zsófia, Járdánházy, Anett, Sandi, Dániel, Biernacki, Tamás, Fricska-Nagy, Zsanett, Füvesi, Judit, Bartosik-Psujek, Halina, Kes, Vanja Basic, Berger, Thomas, Berthele, Achim, Drulovic, Jelena, Hemmer, Bernhard, Horakova, Dana, Ledinek, Alenka Horvat, Havrdova, Eva Kubala, Magyari, Melinda, Rejdak, Konrad, Tiu, Cristina, Turcani, Peter, Klivényi, Péter, Kincses, Zsigmond Tamás, Vécsei, László, and Bencsik, Krisztina
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- 2023
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3. Cladribine tablets in people with relapsing multiple sclerosis: A real-world multicentric study from southeast European MS centers
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Adamec, Ivan, Jakob, Gregor Brecl, Rajda, Cecilia, Drulović, Jelena, Radulović, Ljiljana, Kes, Vanja Bašić, Lazibat, Ines, Rimac, Julija, Cindrić, Igor, Gržinčić, Tihana, Abičić, Ana, Barun, Barbara, Gabelić, Tereza, Gomezelj, Sarah, Mesaroš, Šarlota, Pekmezović, Tatjana, Klivényi, Péter, Skorić, Magdalena Krbot, and Habek, Mario
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- 2023
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4. Voxel-based asymmetry of the regional gray matter over the inferior temporal gyrus correlates with depressive symptoms in medicated patients with major depressive disorder
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Kocsis, Krisztián, Holczer, Adrienn, Kazinczi, Csaba, Boross, Katalin, Horváth, Regina, Németh, Luca Viola, Klivényi, Péter, Kincses, Zsigmond Tamás, and Must, Anita
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- 2021
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5. Time-course of kynurenic acid concentration in mouse serum following the administration of a novel kynurenic acid analog
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Zádori, Dénes, Ilisz, István, Klivényi, Péter, Szatmári, István, Fülöp, Ferenc, Toldi, József, Vécsei, László, and Péter, Antal
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- 2011
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6. The role of kynurenines in disorders of the central nervous system: Possibilities for neuroprotection
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Vamos, Eniko, Pardutz, Arpad, Klivenyi, Peter, Toldi, Jozsef, and Vecsei, Laszlo
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- 2009
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7. Kynurenine metabolism in plasma and in red blood cells in Parkinson's disease
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Hartai, Zsuzsanna, Klivenyi, Peter, Janaky, Tamas, Penke, Botond, Dux, Laszlo, and Vecsei, Laszlo
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- 2005
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8. 24-Hour Near-Infrared Spectroscopy Monitoring of Acute Ischaemic Stroke Patients Undergoing Thrombolysis or Thrombectomy: A Pilot Study.
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Annus, Ádám, Nagy, András, Vécsei, László, and Klivényi, Péter
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Introduction: Monitoring of acute ischaemic stroke patients during thrombolysis or thrombectomy is based mostly on frequent physical examinations, since no objective measurement of cerebrovascular haemodynamics is available in routine clinical practice. Near-infrared spectroscopy (NIRS) is a bed-side, noninvasive assessment tool that could help monitor these patients and potentially guide therapeutic interventions. Our goal in this pilot study was to investigate whether NIRS is a suitable method to monitor leptomeningeal collateral circulation via changes in cortical oxygen saturation in the first 24 hours of acute ischaemic stroke.Patients and Methods: Our study included 5 patients with acute anterior circulation infarcts. All patients received thrombolytic therapy and 1 had thrombectomy. 24-hour continuous NIRS monitoring was performed on all participants.Results: We aimed to give a detailed description of each NIRS recording and explain how the observed findings could correlate with changes in anterior watershed territory collateral circulation and clinical outcome.Conclusion: Our pilot study supports the use of NIRS monitoring in acute ischaemic stroke. We believe that this technique could provide real-time information on the dynamic changes of leptomeningeal collateral circulation and help monitor the effects of thrombolysis and thrombectomy. [ABSTRACT FROM AUTHOR]- Published
- 2019
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9. Pediatric multiple sclerosis and fulminant disease course: Features and approaches to treatment – A case report and review of the literature.
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Sandi, Dániel, Bereg, Edit, Biernacki, Tamás, Vörös, Erika, Klivényi, Péter, Bereczki, Csaba, Vécsei, László, and Bencsik, Krisztina
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Multiple sclerosis (MS) is the autoimmune, neurodegenerative disease of the central nervous system (CNS). Typically, it affects the young adult population, however, up to 10% of the cases, it can develop in childhood. Atypical manifestations, such as the tumefactive variant (tMS) or acute disseminated encephalomyelitis (ADEM), especially coupled with fulminant disease course, are even more rare and pose a considerable differential diagnostic and therapeutic challenge. Recently, the therapeutic strategy on the use of disease modifying therapies (DMTs) in MS has shifted to the direction of a more individualized approach, that takes the personal differences heavily into account, in particular regard to the activity and prognosis of the disease. Despite this change has only been applied to adults yet, it is plausible to predict, that it will soon be applied to pediatric patients as well, particularly, as several randomized studies are under way concerning DMTs in pediatric populations. To our best knowledge, we are the first to report a successful natalizumab treatment of pediatric fulminant tMS, in case of a 13.5 years old girl. We feel that this report demonstrates the need of early and adequate treatment in such an aggressive case, because it can reverse the course of a possibly fatal disease. [ABSTRACT FROM AUTHOR]
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- 2018
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10. Connection between microstructural alterations detected by diffusion MRI and cognitive dysfunction in MS: A model-free analysis approach.
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Faragó, Péter, Tóth, Eszter, Szabó N, Nikoletta, Kocsis, Krisztián, Kincses, Bálint, Bozsik, Bence, Veréb, Dániel, Biernacki, Tamás István, Király, András, Sandi, Dániel, Bencsik, Krisztina, Klivényi, Péter, Vécsei, László, and Kincses, Zsigmond Tamás
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• Diffusion parameters predicting performance on SDMT and BVMT tests could be well separated from those related to CVLT. • Patterns of diffusion parameters representing demyelination and axonal damage in certain spatial arrangements corresponds to cognitive dysfunctions. • About one quarter of the cognitive impairment's variance may be explained by putative axonal damage in MS, which has presumably little potential for regeneration. Cognitive decline is a prominent symptom of MS. Clear connection between cognitive status and white matter microstructural changes has not been unequivocally observed to date. To characterise the relationship between white matter microstructure and cognitive performance a partial least squares (PLS) approach was used. 53 RR MS patients' T1 and DTI images and BICAMS subtests were used in our analysis. Standard FSL pipeline was used to obtain diffusion parameters. A PLS approach was applied to reveal the diffusion parameter patterns responsible for the cognitive dysfunction. The first latent variable (LV) was mainly associated with demyelination, while the second and third explained axonal damage. While the first two LV represented mainly Brief Visuospatial Memory Test (BVMT) and Single Digit Modality Test (SDMT), the third LV depicted diffusion alterations mainly the verbal subtest. The first LVs spatial map showed demyelination in the corpus callosum. The second LVs spatial map showed the diffusion alterations in the thalamus. The third LV depicted diffusion alterations in the putative left superior longitudinal fascicle. Visual memory demanding tasks versus language functions depend on distinct patterns of diffusion parameters and the spatial organisation. Axial diffusivity alterations, a putative marker of irreversible axonal loss explained around 20% of variability in the cognitive functions. [ABSTRACT FROM AUTHOR]
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- 2022
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11. Mitochondrial disturbances, excitotoxicity, neuroinflammation and kynurenines: Novel therapeutic strategies for neurodegenerative disorders
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Zádori, Dénes, Klivényi, Péter, Szalárdy, Levente, Fülöp, Ferenc, Toldi, József, and Vécsei, László
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NEURODEGENERATION , *KYNURENINE , *HUNTINGTON disease , *LIPID peroxidation (Biology) , *CEREBRAL ischemia , *METHYL aspartate receptors , *NEUROTOXIC agents , *MITOCHONDRIAL pathology - Abstract
Abstract: A mitochondrial dysfunction causes an abatement in ATP production, the induction of oxidative damage and the propagation of cell death pathways. It is additionally closely related to both glutamate excitotoxicity and neuroinflammation. All of these interconnected aspects of a cellular dysfunction are involved in the pathogenesis of numerous neurological disorders, including those with an acute (e.g. ischemic stroke) or a chronic (e.g. Huntington''s disease) onset. Both acute and chronic neurodegenerative disorders have been demonstrated to involve multiple imbalances of the kynurenine pathway metabolism in the pathogenesis of the disease. As regards neuroactive compounds featuring in the pathway, quinolinic acid is a specific agonist of N-methyl-d-aspartate receptors, and a potent neurotoxin with additional and marked free radical-producing and lipid peroxidation-inducing properties. The toxic effects of 3-hydroxy-L-kynurenine are mediated by free radicals. Besides the possibility of increasing brain kynurenic acid concentrations, L-kynurenine may have vasoactive properties, too. Kynurenic acid has proven to be neuroprotective in several experimental settings, but in consequence of its pharmacokinetic properties it is not applicable as systemic administration in human cases. The aim of this short review is to emphasize the common features of cerebral ischemia and Huntington''s disease and to highlight therapeutic strategies targeting the kynurenine pathway. [Copyright &y& Elsevier]
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- 2012
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12. Re-analysis of the Hungarian amyotrophic lateral sclerosis population and evaluation of novel ALS genetic risk variants.
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Nagy, Zsófia Flóra, Pál, Margit, Salamon, András, Kafui Esi Zodanu, Gloria, Füstös, Dalma, Klivényi, Péter, and Széll, Márta
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• ATXN2 intermediate repeat expansions may be ALS-associated among Hungarian patients. • ATXN1 intermediate alleles were found more frequently than noted from Europe. • Variants of uncertain significance were detected in genes linked to ALS before. • Neither SMN1 nor SMN2 confer genetic risk of ALS in the Hungarian population. Amyotrophic lateral sclerosis (ALS) is a presently incurable neurodegenerative disease. Some genes have a causal relationship to ALS, others act as susceptibility and/or risk factors. We aimed to elucidate the role of 14 ALS-related genes in the Hungarian ALS population of 183 patients. Mutation screening of major ALS genes was performed. SMN1 and SMN2 genes were examined by multiplex ligation-dependent probe-amplification assay; intermediate repeat expansions in the ATXN1 and ATXN2 genes were analyzed by fragment analysis. Additional variants in putative ALS genes were screened from previously acquired next generation sequencing data. We confirmed the repeat expansion of the C9orf72, ATXN1 and ATXN2 genes as ALS risk factors in this Hungarian cohort. Additionally, we identified a pathogenic SOD1 mutation and suggested its founder effect. A likely pathogenic variant in the MFSD8 gene was detected, and variants of interest were uncovered in the ANXA11 and GLT8D1 genes. We provide valuable data as part of the growing body of work on population-specific aspects of the genetic background of ALS. [ABSTRACT FROM AUTHOR]
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- 2022
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13. The Effects of Bilateral Theta-burst Stimulation on Executive Functions and Affective Symptoms in Major Depressive Disorder.
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Holczer, Adrienn, Németh, Viola Luca, Vékony, Teodóra, Kocsis, Krisztián, Király, András, Kincses, Zsigmond Tamás, Vécsei, László, Klivényi, Péter, and Must, Anita
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MENTAL depression , *EXECUTIVE function , *AFFECT (Psychology) , *COGNITION disorders , *HAMILTON Depression Inventory - Abstract
• Bilateral theta-burst stimulation results in reduced depressive symptoms. • No effect is present on executive functions after the stimulation. • Psychomotor speed can potentially be increased by theta-burst stimulation. Major depressive disorder (MDD) is characterized by severe affective as well as cognitive symptoms. Moreover, cognitive impairment in MDD can persist after the remission of affective symptoms. Theta-burst stimulation (TBS) is a promising tool to manage the affective symptoms of major depressive disorder (MDD); however, its cognition-enhancing effects are sparsely investigated. Here, we aimed to examine whether the administration of bilateral TBS has pro-cognitive effects in MDD. Ten daily sessions of neuronavigated active or sham TBS were delivered bilaterally over the dorsolateral prefrontal cortex to patients with MDD. The n-back task and the attention network task were administered to assess working memory and attention, respectively. Affective symptoms were measured using the 21-item Hamilton Depression Rating Scale. We observed moderate evidence that the depressive symptoms of patients receiving active TBS improved compared to participants in the sham stimulation. No effects of TBS on attention and working memory were detected, supported by a moderate-to-strong level of evidence. The effects of TBS on psychomotor processing speed should be further investigated. Bilateral TBS has a substantial antidepressive effect with no immediate adverse effects on executive functions. [ABSTRACT FROM AUTHOR]
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- 2021
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14. Assessment of risk factor variants of LRRK2, MAPT, SNCA and TCEANC2 genes in Hungarian sporadic Parkinson's disease patients.
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Boros, Fanni A., Török, Rita, Vágvölgyi-Sümegi, Evelin, Pesei, Zsófia Gabriella, Klivényi, Péter, and Vécsei, László
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PARKINSON'S disease , *ALOPECIA areata , *RESTRICTION fragment length polymorphisms , *RISK assessment , *DISEASE risk factors , *FAMILY history (Medicine) - Abstract
• G2385R and R1628P LRRK2 variants are absent in the Hungarian population. • The minor allele of the risk factor S1647T variant is more frequent among healthy male individuals compared to patients. • The protective rs356186 SNCA variant is significantly more frequent in homozygous form among controls than in PD patients. • The rs356186 SNCA variant is significantly more frequent in heterozygous form among LOPD patients compared to controls. • No significant differences were detected in the case of rs1491923, R1398H, N551K, rs2583988, rs1052553, rs10788972 variants. Parkinson's disease is the second most common neurodegenerative disease. Lifestyle, environmental effects and several genetic factors have been proposed to contribute to its development. Though the majority of PD cases do not have a family history of disease, genetic alterations are proposed to be present in 60 percent of the more common sporadic cases. The aim of this study is to evaluate the frequency of PD related specific risk variants of LRRK2 , MAPT , SNCA and PARK10 genes in the Hungarian population. Out of the ten investigated polymorphisms three are proposed to have protective effect and seven are putative risk factors. For genotyping, TaqMan allelic discrimination and restriction fragment length polymorphism method was used. LRRK2 mutations were investigated among 124 sporadic PD patients and 128 healthy controls. MAPT and SNCA variant frequencies were evaluated in a group of 123 patients and 122 controls, while PARK10 variant was studied in groups of 121 patients and 113 controls. No significant difference could be detected in the frequencies of the investigated MAPT and PARK10 variants between the studied Hungarian PD cases and controls. The minor allele of the risk factor S1647T LRRK2 variant was found to be more frequent among healthy male individuals compared to patients. Moreover, in the frequency of one of the investigated SNCA variant a significant intergroup difference was detected. The minor allele (A) of rs356186 is proposed to be protective against developing the disease. In accord with data obtained in other populations, the AA genotype was significantly more frequent among Hungarian healthy controls compared to patients. Similarly, a significant difference in genotype distribution was also found in comparison of patients with late onset disease to healthy controls, which was due to the higher frequency of AG genotype among patients. The frequencies of different gene variants show great differences in populations. Assessment of the frequency of variants of PD related genes variants is important in order to uncover the pathomechanisms underlying the disease, and to identify potential therapeutic targets. This is the first comprehensive study focusing on these genetic variants in the population of East-Central European region. Our results extend the knowledge on the world wide occurrence of these polymorphisms by demonstrating the occurrence of specific alleles and absence of others in Hungarian PD patients. [ABSTRACT FROM AUTHOR]
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- 2019
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15. Levodopa/carbidopa intestinal gel can improve both motor and non-motor experiences of daily living in Parkinson's disease: An open-label study.
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Juhász, Annamária, Aschermann, Zsuzsanna, Ács, Péter, Janszky, József, Kovács, Márton, Makkos, Attila, Harmat, Márk, Tényi, Dalma, Karádi, Kázmér, Komoly, Sámuel, Takáts, Annamária, Tóth, Adrián, Nagy, Helga, Klivényi, Péter, Dibó, György, Dézsi, Lívia, Zádori, Dénes, Annus, Ádám, Vécsei, László, and Varannai, Lajos
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PARKINSON'S disease treatment , *CARBIDOPA , *DOPA , *DRUG efficacy , *QUALITY of life , *THERAPEUTICS , *INTESTINAL physiology , *DRUG therapy for Parkinson's disease , *PARKINSON'S disease , *DOPAMINE agents , *PHARMACEUTICAL gels , *ANTIPARKINSONIAN agents , *COMBINATION drug therapy , *COMPARATIVE studies , *FUNCTIONAL assessment , *LONGITUDINAL method , *RESEARCH methodology , *MEDICAL cooperation , *QUESTIONNAIRES , *RESEARCH , *ACTIVITIES of daily living , *EVALUATION research , *TREATMENT effectiveness , *SEVERITY of illness index , *PSYCHOLOGY - Abstract
Background: Levodopa/carbidopa intestinal gel therapy (LCIG) can efficiently improve several motor and non-motor symptoms of advanced Parkinson's disease (PD). The recently developed Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) improved the original UPDRS making it a more robust tool to evaluate therapeutic changes. However, previous studies have not used the MDS-UPDRS and the Unified Dyskinesia Rating Scale (UDysRS) to assess the efficacy of LCIG.Objectives: Our aim was to determine if the MDS-UPDRS and UDysRS could detect improvement in the experiences of daily living following 1-year LCIG treatment.Methods: In this prospective, multicenter, open-label study, 34 consecutive patients undergoing LCIG treatment were enrolled. Patients were examined twice: prior to LCIG initiation and 12 months later. Impact of PD-related symptoms and dyskinesia was assessed by the MDS-UPDRS and UDysRS.Results: Non-motor Experiences of Daily Living part of MDS-UPDRS improved from 20 (median, interquartile-range, IQR:14-23) to 16 points (median, IQR:12-20, p = 0.044) and the Motor Experiences of Daily Living ameliorated from 24 (median, IQR:20-29) to 18 points (median, IQR:13-25, p = 0.025). Health-related quality of life, measured by PDQ-39, also improved from 35.4 (median, IQR:26.9-50.3) to 27.0 (median, IQR:21.3-31.4) points (p = 0.003). The total score of UDysRS decreased from 47 (median, IQR:36-54) to 34 (median, IQR:21-45) points (p = 0.003).Conclusions: As far as the authors are aware of, our paper is the first to evaluate the impact of LCIG on dyskinesia by the means of UDysRS. Changes in MDS-UPDRS and UDysRS confirm that LCIG treatment can efficiently improve experiences of daily living in advanced PD. [ABSTRACT FROM AUTHOR]- Published
- 2017
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16. Effect of subthalamic stimulation on distal and proximal upper limb movements in Parkinson's disease.
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Tamás, Gertrúd, Kelemen, Andrea, Radics, Péter, Valálik, István, Heldman, Dustin, Klivényi, Péter, Vécsei, László, Hidasi, Eszter, Halász, László, Kis, Dávid, Barsi, Péter, Golopencza, Péter, and Erőss, Loránd
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PARKINSON'S disease , *ARM physiology , *MOTOR ability , *NEURAL stimulation , *DOPAMINERGIC mechanisms , *SUBTHALAMIC nucleus - Abstract
Introduction A different innervation pattern of proximal and distal muscles from the contra- and ipsilateral motor circuits raises the question as to whether bilateral, contra- and ipsilateral subthalamic stimulation may have different effects on the distal and proximal movements of the upper limb. To answer this question, we performed kinematic analyzes in patients with Parkinson's disease. Methods Twenty-eight Parkinsonian patients treated by bilateral subthalamic stimulation were examined with an age-matched control group of 28 healthy subjects. They performed 14 s of finger tapping, hand grasping and pronation-supination. The patient group performed these sessions in four conditions (BOTH ON, BOTH OFF, CONTRA ON, IPSI ON) after withdrawal of dopaminergic medication for 12 h and a fifth condition after taking medication (BOTH ON-MED ON). A motion sensor with a three-dimensional gyroscope was worn on the index finger. Speed, amplitude, rhythm and decrement of movements were calculated and compared across these conditions. Results Speed and amplitude of the more distal movements were improved similarly by contra- and bilateral stimulation. Bilateral stimulation was more effective than contralateral stimulation for the more proximal movements. Contra- and bilateral stimulation ameliorated the rhythm similarly in each movement task. Decrement of distal and proximal movements was not affected by the stimulation conditions. Conclusion This is the first study to show that the outcome of bi- and unilateral subthalamic stimulation on proximal and distal upper limb movements should be evaluated separately postulating the different somatotopic organization of subloops in the cortico-basal ganglia motor circuits. [ABSTRACT FROM AUTHOR]
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- 2016
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17. Relevance of defensin β-2 and α defensins (HNP1-3) in Alzheimer's disease.
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Szekeres, Martha, Ivitz, Eszter, Datki, Zsolt, Kálmán, János, Pákáski, Magdolna, Várhelyi, Zoltán P., Klivényi, Péter, Zadori, Dénes, Somogyvári, Ferenc, Szolnoki, Zoltán, Vécsei, László, and Mándi, Yvette
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ALZHEIMER'S patients , *DEFENSINS , *DNA copy number variations , *GENETICS of Alzheimer's disease , *CEREBROSPINAL fluid ,PSYCHIATRIC research - Abstract
The DEFB4 gene copy numbers were investigated in 206 AD patients and in 250 controls. The levels of the human defensin β−2 (hBD2) and α-defensins (HNP 1-3) in the sera and in the cerebrospinal fluid (CSF) of the patients and the controls were determined. Higher copy numbers of the DEFB4 gene was observed in AD patients as compared with the controls. The levels of hBD-2 and HNP 1-3 were significantly elevated in the sera and in the CSF of the AD patients These data suggest that both defensin β−2 and α-defensins have potential role in the development of AD. [ABSTRACT FROM AUTHOR]
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- 2016
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18. An assessment of the frequency of mutations in the GBA and VPS35 genes in Hungarian patients with sporadic Parkinson’s disease.
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Török, Rita, Zádori, Dénes, Török, Nóra, Csility, Éva, Vécsei, László, and Klivényi, Péter
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GENETIC mutation , *GENETIC polymorphisms , *GENES , *NEURODEGENERATION , *PROTEINS - Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative disorder, with cases of either familial or sporadic origin. Several polymorphisms in a number of genes have been proved to have an important role in the development of PD. Particular attention has recently been paid to genes of the glucocerebrosidase (GBA) and the vacuolar protein sorting-associated protein 35 (VPS35). In this study, the three most common mutations (L444P, N370S and R120W) of the GBA gene and the D620N mutation of the VPS35 gene were examined in 124 Hungarian patients diagnosed with sporadic PD (SPD) and 122 control subjects. The frequency of the L444P mutation of the GBA gene proved to be higher in the PD patients (2.4%) than in the controls (0%), although the difference was not statistically significant. All the patients who carried the mutant allele were in the early-onset PD (EOPD) group. However, neither the R120W nor the N370S variant of the GBA gene nor D620N mutation of the VPS35 gene were detected among the PD cases or the controls. Even though these results suggest that the studied mutations are quite rare in SPD patients, the most frequent L444P mutation of the GBA gene may be associated with the development of EOPD in the Hungarian population. [ABSTRACT FROM AUTHOR]
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- 2016
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19. The clinical manifestations of two novel SPAST mutations.
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Zádori, Dénes, Máté, Adrienn, Róna-Vörös, Krisztina, Gergev, Gyurgyinka, Zimmermann, Alíz, Nagy, Nikoletta, Széll, Márta, Vécsei, László, Sztriha, László, and Klivényi, Péter
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- 2015
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20. Low dosage of rimonabant leads to anxiolytic-like behavior via inhibiting expression levels and G-protein activity of kappa opioid receptors in a cannabinoid receptor independent manner.
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Zádor, Ferenc, Lénárt, Nikolett, Csibrány, Balázs, Sántha, Miklós, Molnár, Máté, Tuka, Bernadett, Samavati, Reza, Klivényi, Péter, Vécsei, László, Marton, Annamária, Vizler, Csaba, Nagy, György M., Borsodi, Anna, Benyhe, Sándor, and Páldy, Eszter
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DRUG dosage , *RIMONABANT , *PROTEIN expression , *TRANQUILIZING drugs , *G protein coupled receptors , *OPIOID receptors , *CANNABINOID receptors , *THERAPEUTICS - Abstract
What is known There is an increasing number of studies demonstrating the direct effect of the cannabinoid receptor 1 (CB 1 ) antagonist/inverse agonist rimonabant on the opioid system. The kappa opioid receptors (KORs) are well known to mediate depression- and anxiety-like behavior. Clinical studies on chronic rimonabant administration have revealed that rimonabant leads to a very similar pathophysiology, suggesting a potential impact of rimonabant on KORs. Objectives Our objectives were to examine the putative effects of rimonabant on KOR ligand binding, G-protein activity, protein expression and how all these contribute to the development of depression- and anxiety-like behavior. Results In Chinese hamster ovary (CHO) cell membranes transfected with rat KOR (CHO-rKOR) rimonabant inhibited KOR agonist [ 3 H]U69593 binding in the micromolar range in competition binding experiments and specifically reduced KOR basal activity at lower micromolar concentrations in [ 35 S]GTPγS binding assays. Rimonabant significantly inhibited dynorphin (1–11)-induced [ 35 S]GTPγS binding in micromolar range in CHO-rKOR cells, CB 1 knockout (CB 1 K.O.) and CB 1 /CB 2 double knockout mouse forebrain membranes. A single dose of i.p. 0.1 mg/kg rimonabant significantly reduced dynorphin (1–11)-induced KOR G-protein activity and KOR protein expression levels 24 h following the administration in both wild type and CB 1 K.O. mice forebrain. Furthermore, in elevated plus maze mice showed an anxiolytic-like effect upon rimonabant injection that could be reversed by 1 mg/kg KOR antagonist norbinaltorphimine. The anxiolytic-like effects were further confirmed with the light–dark box test. Conclusion Rimonabant reduced KOR ligand binding, receptor mediated G-protein activity and protein expression level, which overall leads to altered anxiety-like behavior. [ABSTRACT FROM AUTHOR]
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- 2015
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21. Valproate ameliorates the survival and the motor performance in a transgenic mouse model of Huntington's disease
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Zádori, Dénes, Geisz, Andrea, Vámos, Enikő, Vécsei, László, and Klivényi, Péter
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VALPROIC acid , *SURVIVAL analysis (Biometry) , *MOTOR ability , *TRANSGENIC mice , *HUNTINGTON disease , *NEURODEGENERATION , *PATHOLOGICAL physiology - Abstract
Abstract: Huntington''s disease (HD) is one of the chronic devastating neurodegenerative disorders. The pathophysiological processes clearly involve both excitotoxicity and reduced gene transcription due to the decreased level of histone acetylation, accompanied by the loss of γ-aminobutyric acidergic (GABAergic) medium-sized spiny neurons in the striatum as a pathological hallmark of HD. Thus, the antiepileptic drug valproate, which has proved GABAergic, antiexcitotoxic and histone deacetylase inhibitor effects, might be of value by exerting a beneficial neuroprotective effect. We have now tested this drug in the N171-82Q transgenic mouse model of HD, following its chronic intraperitoneal administration in a daily dose of 100 mg/kg. Valproate significantly prolonged the survival of the transgenic mice and significantly ameliorated their diminished spontaneous locomotor activity, without exerting any noteworthy side-effect on their behaviour or the striatal dopamine content at the dose administered. The beneficial effect of valproate is probably explained by its complex pharmacological activity. As several previous clinical trials carried out with valproate did not indicate any positive effect in HD, it is worth considering the design of new studies based on a well-planned treatment regime with higher dose, using valproate in monotherapy or in combination therapy with a high number of participating patients. [Copyright &y& Elsevier]
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- 2009
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22. Increased level of NEAT1 long non-coding RNA is detectable in peripheral blood cells of patients with Parkinson's disease.
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Boros, Fanni Annamária, Maszlag-Török, Rita, Vécsei, László, and Klivényi, Péter
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PARKINSON'S disease , *NON-coding RNA , *BLOOD cells , *DISEASE duration , *BRAIN diseases - Abstract
• NEAT1 lncRNA regulates cellular and mitochondrial homeostasis. • Changes in NEAT1 level were reported in PD brain and in models of the disease. • We detected up-regulated NEAT1 level in leukocytes of PD patients. • NEAT1 up-regulation was most prominent among patients with long disease duration. Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder that poses serious burden to individuals and society as well. Although a number of PD associated genetic factors have been identified, the molecular mechanism of the disease so far has not been completely elucidated. Involvement of long non-coding RNAs (lncRNAs) in the pathology of neurodegenerative disorders is attracting increased interest because of the diverse mechanisms lncRNAs affect gene expression and cellular homeostasis at different levels. We aimed to test the feasibility of detecting alterations in lncRNA levels in easily accessible samples of PD patients by routine laboratory technique. By narrowing the number of selected lncRNAs implicated in neurodegeneration and increasing the number of PD samples included, we found one out of 41 lncRNAs readily detectable in increased level in peripheral blood of PD patients. We detected NEAT1 to be significantly up-regulated in PD patients in multiple comparisons. NEAT1 is the core element of nuclear paraspeckles and it plays role in regulation of transcription, mRNA and miRNA levels, mitochondrial and cellular homeostasis. Our finding is in accord with recent data demonstrating changes in the level of NEAT1 in neurons of PD patients and in several models of the disease. However, to our knowledge this is the first study to report NEAT1 up-regulation in blood of PD patients. Identification of altered expression of this lncRNA in the periphery might help to a better understanding of the mechanisms underlying PD, and can contribute to the identification of new therapeutic targets and disease markers. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
23. Genetic analysis of the SOD1 and C9ORF72 genes in Hungarian patients with amyotrophic lateral sclerosis.
- Author
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Tripolszki, Kornélia, Csányi, Bernadett, Nagy, Dóra, Ratti, Antonia, Tiloca, Cinzia, Silani, Vincenzo, Kereszty, Éva, Török, Nóra, Vécsei, László, Engelhardt, József I., Klivényi, Péter, Nagy, Nikoletta, and Széll, Márta
- Subjects
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AMYOTROPHIC lateral sclerosis , *HUNGARIANS , *MOTOR neurons , *GENETIC mutation , *ETIOLOGY of diseases , *PATIENTS - Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the death of motor neurons. To date, more than 20 genes have been implicated in ALS, and of these, the 2 most frequently mutated are the superoxide dismutase 1 (SOD1) gene and the chromosome 9 open reading frame 72 (C9ORF72) gene. In this study, we aimed to investigate the contribution of these 2 Mendelian genes to the development of the disease in Hungarian ALS patients (n = 66). Direct sequencing of the SOD1 gene revealed a novel (p.Lys91ArgfsTer8) and 3 recurrent heterozygous mutations (p.Val14Met, p.Asp90Ala, and p.Leu144Phe) in 5 patients. The novel p.Lys91ArgfsTer8 mutation led to a frameshift causing the addition of 8 new amino acids, including a premature stop codon at position 99. The GGGGCC hexanucleotide repeat expansion of the C9ORF72 gene was present in 1 ALS patient. This study represents the first genetic analysis of 2 major ALS causative genes in a cohort of Hungarian ALS patients and contributes to the further understanding of the genetic and phenotypic diversity of ALS. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
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