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Biomedical subjects

Zoltán Szabó

Publications and source records attributed to Zoltán Szabó.

At least 19 recordsLinked to original sources
PubMed2006

Structure, equilibrium and ligand exchange dynamics in the binary and ternary dioxouranium(VI)-ethylenediamine-N,N'-diacetic acid-fluoride system: A potentiometric, NMR and X-ray crystallographic study.

The structure, thermodynamics and kinetics of the binary and ternary uranium(VI)-ethylenediamine-N,N'-diacetate (in the following denoted EDDA) fluoride systems have been studied using potentiometry, 1H, 19F NMR spectroscopy and X-ray diffraction. The UO2(2+)-EDDA system could be studied up to -log[H3O+] = 3.4 where the formation of two binary complexes UO2(EDDA)(aq) and UO2(H3EDDA)3+ were identified, with equilibrium constants logbeta(UO2EDDA) = 11.63 +/- 0.02 and logbeta(UO2H3EDDA3+) = 1.77 +/- 0.04, respectively. In the ternary system the complexes UO2(EDDA)F-, UO2(EDDA)(OH)- and (UO2)2(mu-OH)2(HEDDA)2F2(aq) were identified; the latter through 19F NMR. 1H NMR spectra indicate that the EDDA ligand is chelate bonded in UO2(EDDA)(aq), UO2(EDDA)F- and UO2(EDDA)(OH)- while only one carboxylate group is coordinated in UO2(H3EDDA)3+. The rate and mechanism of the fluoride exchange between UO2(EDDA)F- and free fluoride was studied by 19F NMR spectroscopy. Three reactions contribute to the exchange; (i) site exchange between UO2(EDDA)F- and free fluoride without any net chemical exchange, (ii) replacement of the coordinated fluoride with OH- and (iii) the self dissociation of the coordinated fluoride forming UO2(EDDA)(aq); these reactions seem to follow associative mechanisms. (1)H NMR spectra show that the exchange between the free and chelate bonded EDDA is slow and consists of several steps, protonation/deprotonation and chelate ring opening/ring closure, the mechanism cannot be elucidated from the available data. The structure (UO2)2(EDDA)2(mu-H2EDDA) was determined by single crystal X-ray diffraction and contains two UO2(EDDA) units with tetracoordinated EDDA linked by H2EDDA in the "zwitterion" form, coordinated through a single carboxylate oxygen from each end to the two uranium atoms. The geometry of the complexes indicates that there is no geometric constraint for an associative ligand substitution mechanism.

Crystallography, X-Ray↗
PubMed2006

Sensitivity to reward and punishment and the prefrontal cortex in major depression.

BACKGROUND: Patients with major depressive disorder (MDD) show neuropsychological impairments, including deficient executive functions and altered sensitivity to reward and punishment. METHODS: Executive functions (Wisconsin Card Sorting Test, WCST) and contingency learning based on the cumulative effect of reward and punishment (Iowa Gambling Test, IGT) were assessed in 30 medicated patients with unipolar MDD and in 20 healthy control volunteers. In the classic ABCD version of the IGT, advantageous decks are characterized by immediate small reward but even smaller future punishment. In the modified EFGH version, advantageous decks are characterized by immediate large punishment but even larger future reward. RESULTS: Patients with MDD were impaired in the WCST and in the ABCD version of the IGT but showed normal performances on the EFGH task. Depression, but not executive dysfunctions, significantly predicted performances on the EFGH task: less severe depressive symptoms were associated with better performances on the EFGH task. LIMITATIONS: The sample size was small and only few neuropsychological tests were used. Unmedicated patients were not assessed. Individual personality style, response strategies, and behavioral impulsivity were not investigated. CONCLUSIONS: Medicated patients with MDD show altered sensitivity to reward and punishment: immediate large reward enhanced related response patterns even when the strategy was disadvantageous and immediate large punishment did not prohibit related response patterns. Impairments in emotional decision-making were not a pure consequence of executive dysfunctions.

Adult↗
PubMed2005

Combinatorial multinuclear NMR and X-ray diffraction studies of uranium(VI)-nucleotide complexes.

The complex formation of uranium(VI) with four nucleotides, adenosine- (AMP), guanosine- (GMP), uridine- (UMP), and cytidine-monophosphate (CMP), has been studied in the alkaline pH range (8.5-12) by (1)H, (31)P, (13)C, and (17)O NMR spectroscopy, providing spectral integral, chemical shift, homo- and heteronuclear coupling, and diffusion coefficient data. We find that two and only two complexes are formed with all ligands in the investigated pH region independently of the total uranium(VI) and ligand concentrations. Although the coordination of the 5'-phosphate group and the 2'- and 3'-hydroxyl groups of the sugar unit to the uranyl ions is similar to that proposed earlier ("Feldman complex"), the number and the structures of the complexes are different. The uranium-to-nucleotide ratio is 6:4 in one of the complexes and 3:3 in the other one, as unambiguously determined by a combinatorial approach using a systematic variation of the ratio of two ligands in ternary uranium(VI)-nucleotide systems. The structure of the 3:3 complex has been determined by single-crystal diffraction as well, and the results confirm the structure proposed by NMR in aqueous solution. The results have important implications on the synthesis of oligonucleotides.

Adenosine Monophosphate↗
PubMed2005

Dopamine transporter availability in medication free and in bupropion treated depression: a 99mTc-TRODAT-1 SPECT study.

BACKGROUND: Bupropion is thought to exert its antidepressive effect by blocking the dopamine transporter (DAT). The purpose of this study was to evaluate the DAT activity in depressed patients by means of 99mTc-TRODAT-1 SPECT in relation to the efficacy of bupropion treatment. METHODS: In 12 healthy controls and 16 depressed patients the baseline DAT activity was examined. Nine of the 16 patients went through an additional second SPECT investigation, after 4 weeks of bupropion treatment. RESULTS: In the depressed patients, the baseline DAT striatum-occipital ratio (SOR) (1.04+/-.36, mean+/-SD) was not significantly different from that in the control group (1.12+/-.33) (p>.05). Correlation was found between baseline SOR and HAM-D score change (r=-.745, p=.02) of the bupropion treated patients. The average DAT occupancy due to the bupropion treatment was 20.84+/-27.7%. No significant correlation between the therapeutical effectiveness and the occupancy was observed. LIMITATIONS: One of the limiting factors of our study has been the lack of drug monitoring. CONCLUSIONS: In good agreement with other PET studies, we found 20.84% DAT occupancy during bupropion treatment. The lack of correlation between the efficacy of therapy and occupancy of DAT may raise the question as to whether other mechanisms are involved in the effect of bupropion.

Adult↗
PubMed2005

Two major interacting chromosome loci control disease susceptibility in murine model of spondyloarthropathy.

Autoimmune spondylitis was induced in BALB/c mice and their MHC-matched (BALB/c x DBA/2)F1 and F2 hybrids by systemic immunization with cartilage/intervertebral disk proteoglycan (PG). As in human ankylosing spondylitis, the MHC was the major permissive genetic locus in murine PG-induced spondylitis (PGIS). Two major non-MHC chromosome loci with highly significant linkage were found on chromosomes 2 (Pgis2) and 18 (Pgis1) accounting for 40% of the entire F2 trait variance. The dominant spondylitis-susceptibility allele for Pgis2 locus is derived from the BALB/c strain, whereas the Pgis1 recessive allele was present in the disease-resistant DBA/2 strain. The Pgis1 locus significantly affected the disease-controlling Pgis2 locus, inducing as high incidence of spondylitis in F2 hybrids as was found in the spondylitis-susceptible parent BALB/c strain. Additional disease-controlling loci with suggestive linkage were mapped to the chromosomes 12, 15, and 19. Severity of spondylitis in F2 mice positively correlated with serum levels of amyloid A, IL-6, and Pg-specific Abs, and showed negative correlation with Ag-induced T cell proliferation, IFN-gamma, IL-4, and TNF-alpha production. A major locus controlling serum IL-6 was found on chromosome 14 near osteoclast differentiation factor Tnfsf11. Locus on chromosome 11 near the Stat3 and Stat5 genes controlled serum level of the Ig IgG2a isotype. The two major genetic loci Pgis1 and Pgis2 of murine spondylitis were homologous to chromosome regions in human genome, which control ankylosing spondylitis in human patients. Thus, this animal model of experimentally induced spondylitis might facilitate the identification of spondylitis-susceptibility genes in humans.

Animals↗
PubMed2005

[The place of estramustine in the treatment of prostate cancer].

INTRODUCTION/AIMS: Prostate cancer is a dynamic disease. Androgen ablation is palliative, and does not cure advanced prostate cancer. The hormone-sensitive cells die, and the hormone-resistant cells come into excess; the disease then progresses, which results in a deterioration of the condition of the patient. The theoretical basis of the curing strategy is the fact that the prostate tumour itself changes during the progression; the molecular determinants of the resistance are present in the varying stages of the disease. The treatment of advanced prostate cancer remains unsolved; it is a well-known fact that a hormone-resistant state develops after the primary treatment forms (androgen withdrawal). The drug of choice for the secondary treatment is estramustine. This can be utilized as monotherapy or in combination. METHODS: In the present study, the results of estramustine treatment of 79 patients with advanced prostate cancer were evaluated. The preparation, known and clinically applied for more than 20 years, was studied in 12 centres. RESULTS: The mean prostate-specific antigen level improved for 6 months, but rose from the 9th month on. The improvement in the subjective condition of the patients paralleled the change in the prostate-specific antigen level. The shortness of the improvement was a consequence of the very high prostate-specific antigen level and the poor general condition. CONCLUSIONS: Estramustine administration is recommended when the prostate-specific antigen level becomes more than doubled following the primary treatment. At a starting prostate-specific antigen level of >100 ng/ml, the treatment leads to total androgen blockade. If the prostate-specific antigen level has not decreased after treatment for 3 months, the secondary strategy is to apply chemotherapy.

Aged↗
PubMed2005

Genetic control of experimental spondylarthropathy.

OBJECTIVE: To characterize experimentally induced spondylarthropathy (SpA) in arthritis-susceptible inbred mice and in their F(1) and F(2) hybrid generations of susceptible and resistant mouse strains. METHODS: SpA was induced in susceptible BALB/c and C3H/HeJCr (C3H) strains of mice, and in their F(1) and F(2) generations derived from intercrosses with arthritis- and/or spondylitis-resistant DBA/2 and DBA/1 parent strains, by systemic immunization with cartilage proteoglycan (PG) aggrecan. The incidence and severity of PG-induced spondylitis (PGIS) were scored histologically, and these scores for spine involvement were correlated with serum antibody and cytokine levels and with in vitro T cell responses to cartilage PG. RESULTS: PGIS was induced by systemic immunization with cartilage PG in adjuvant, and approximately 60-70% of susceptible mouse strains and their F(2) hybrids developed spondylitis either with or without arthritis. Adjuvants, particularly those activating the innate immune system and enforcing the Th1 dominance, had significant effects on the outcome and progression of SpA. The DBA/1 strain appeared to carry genes protecting this strain and its F(1) and F(2) hybrids from spondylitis, whereas the DBA/2 strain, although resistant to PGIS, harbored genes permitting PGIS in its hybrid generations. Arthritis- and/or spondylitis-susceptible BALB/c and C3H parent strains and their F(2) hybrids exhibited the highest incidence and severity of spondylitis. CONCLUSION: PGIS, a murine model of autoimmune spondylitis, shows similarities to ankylosing spondylitis. Segregation of susceptibility to PG-induced arthritis (PGIA) from that to PGIS in different genetic crosses suggests that PGIA and PGIS are separate diseases. Therefore, this model allows for the elucidation of genetic components involved in the etiology of SpA, independent of those controlling the susceptibility to PGIA.

Aggrecans↗
PubMed2005

Impact of venlafaxine on gene expression profile in lymphocytes of the elderly with major depression--evolution of antidepressants and the role of the "neuro-immune" system.

Antidepressive drugs offer considerable symptomatic relief in mood disorders and, although commonly discovered by screening with single biological targets, most interact with multiple receptors and signaling pathways. Antidepressants require a treatment regimen of several weeks before clinical efficacy is achieved in patient populations. While the biochemical mechanisms underlying the delayed temporal profile remain unclear, molecular adaptations over time are likely involved. The selective serotonin and noradrenaline reuptake inhibitor, venlafaxine, offers a dual antidepressive action. Its pharmacological behavior, however, is unknown at the genetic level, and it is difficult to monitor in human brain samples. Because the hypothalamic-pituitary-adrenal axis is often severely disrupted in mood disorders, lymphocytes may serve as models of neuropsychiatric conditions. As such, we examined the role of venlafaxine on the gene expression profile of human lymphocytes. DNA microarray was used to measure the expression patterns of multiple genes in human lymphocytes from depressed patients treated with this mood stabilizer. In this self-controlled study, RNAs of control and treated samples were purified, converted into cDNA and labeled with either Cy3 or Cy5, mixed and hybridized to DNA microarrays containing human oligonucleotides corresponding to more than 8,000 genes. Genes that were differentially regulated in response to treatment were selected for follow up on the basis on novelty, gene identity, and level of over-expression/repression, and selected transcripts were profiled by real-time PCR (data have been normalized to beta-actin). Using software analysis of the microarray data, a number of transcripts were differentially expressed between control and treated samples, of which only 57 were found to significantly vary with the "P" value of 0.05 or lower as a result of exposure to venlafaxine. Of these, 31 genes were more highly expressed and 26 transcripts were found to be significantly less abundant. Most selected genes were verified with QRT-PCR to alter. As such, independent verification using QRT-PCR demonstrated the reliability of the method. Genes implicated in ionic homeostasis were differentially expressed, as were genes associated with cell survival, neural plasticity, signal transduction, and metabolism. Understanding how gene expression is altered over a clinically relevant time course of administration of venlafaxine may provide insight into the development of antidepressant efficacy as well as the underlying pathology of mood disorders. These changes in lymphocytes are thought to occur in the brain, and a "neuro-immune system" is proposed by this study.

Aged↗
PubMed2005

Association of rheumatoid arthritis with HLA-DR1 and HLA-DR4 in Hungary.

Susceptibility to and outcome for rheumatoid arthritis (RA) have been associated with particular HLA-DR alleles, but these alleles vary among ethnic groups and geographic areas. The frequency of HLA-DR1 (HLA-DRB1*0101, DRB1*0102) and HLA-DR4 (DRB1*0401, DRB1*0404) alleles is elevated among Caucasian patients with RA. We studied a northeastern Hungarian population of RA patients to determine the frequency of HLA-DR1 and HLA-DR4 phenotypes in this population and to compare it with healthy control subjects, as well as to investigate whether the presence of these alleles could be a marker for RA. We performed HLA-DRB1 genotyping (DRB1*01-DRB1*16) in 83 RA patients and 55 healthy controls using polymerase chain reaction with sequence-specific primers (PCR-SSP). In the case of HLA-DR1- or HLA-DR4-positive patients, the DR1 and DR4 subtypes were also determined. The frequency of HLA-DR4 alleles was significantly higher in RA patients than in controls (31.3 vs. 10.9%; P <.05). HLA-DR1, in particular, tended to be more frequent in patients than in controls (32.5 vs. 18.1%). Among the HLA-DR4 subtypes, DRB1*0401 and DRB1*0404 were the most common alleles found in both groups. However, no significant differences were seen in the frequency of HLA-DRB1*0401 and HLA-DRB1*0404 between RA patients and controls. In contrast, HLA-DRB1*0405 and HLA-DRB1*0408 were significantly more common in RA patients than in control subjects. Among HLA-DR1 subtypes, the DRB1*0101 allele was most commonly detected, but HLA-DRB1*0101 as well as DRB1*0102 and DRB1*0105 were similarly frequent in RA patients and controls. HLA-DR12 was more common among controls than in RA patients (18.1 vs. 0%; P <.05). Our results generally agree with the findings in other Caucasian populations. Nonetheless, we found differences in the frequency of HLA-DR1 and HLA-DR4 subtypes among Hungarian patients compared with reports from other geographic regions (e.g., Finland and Asia). Our data suggest that in northeastern Hungary, HLA-DR4 as well as its subtypes DRB1*0405 and DRB1*0408 may be involved in susceptibility to RA, but HLA-DR1 may not. In addition, the presence of HLA-DR12, at least in Hungary, may protect from this disease.

Adolescent↗
PubMed2005

Effect of hyperlipidemia on QT dispersion in patients without ischemic heart disease.

BACKGROUND: Lipoproteins are known to exert direct and indirect effects on cardiovascular function, but their effects on ventricular repolarization have not yet been clearly elucidated. OBJECTIVES: To assess the effect of hyperlipidemia on the longest QT interval (QTmax) of the 12-lead surface electrocardiogram (ECG) and on QT dispersion (QTd) in type IIb hyperlipidemic patients without myocardial ischemia, and to compare these patients with healthy control subjects. METHODS: Ninety-six hyperlipidemic patients (44 men and 52 women; mean age 53+/-13 years) and 101 healthy control subjects (43 men and 58 women; mean age 46+/-16 years) were examined. Total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol (LDL-C), triglyceride, apolipoprotein (apo) A1, apo B, lipoprotein(a), QTmax and QTd were measured. According to heart rate, corrected QTmax and corrected QTd were also determined. RESULTS: A significant difference was observed between the two groups of subjects with respect to serum cholesterol, LDL-C, triglyceride, apo B, QTmax, corrected QTmax, QTd and corrected QTd. A positive significant correlation was found between cholesterol, triglyceride, LDL-C and all of the studied ECG parameters, between high density lipoprotein cholesterol and QTmax, apo B and QTd, and between body mass index and all of the studied ECG markers. CONCLUSIONS: Hyperlipidemia may have a direct effect on the studied ECG markers.

Adult↗
PubMed2005

[Neuropsychological assessment of the prefrontal cortex in major depressive disorder].

The pathology of the prefrontal cortex (PFC) may play an important role in the development of the symptoms of major depressive disorder. In this study, the authors used the Wisconsin Card Sorting Test (WCST) and the Iowa Gambling Test (IGT) to investigate PFC functions in depression. The WCST investigates cognitive set-shifting abilities, whereas the IGT is sensitive for the cumulative effect of reward and punishment on decision-making. Participants were 20 patients with DSM-IV major depressive disorder and 20 age-, gender-, and education-matched healthy control subjects. The depressed patients showed significant impairment in both tests, but the WCST and IGT scores did not correlate. There was no significant correlation between the test results and the severity of depressive and anxiety symptoms. Our results suggest a global impairment of the PFC in depression, which includes the dorsolateral and ventromedial regions.

Adult↗
PubMed2004

[Cardiovascular manifestations of thyrotoxicosis and thyroid dysfunction caused by amiodarone].

Cardiovascular manifestations of thyrotoxicosis and thyroid dysfunction caused by amiodarone. The cardiovascular symptoms of thyrotoxicosis were described more than two hundred years ago and remained the basis of diagnosis in modern medicine. Myocardium, peripheral circulation and sympathetic nerve system, all affecting cardiovascular hemodynamics, are influenced by thyroid hormones in many ways. Sub-clinical hyperthyroidism is characterized by suppressed thyroid stimulating hormone and normal free triiodothyronine and free thyroxine levels. Cardiovascular symptoms: elevation of heart rate, myocardial contractility, stroke volume, myocardial oxygen consumption, systolic blood pressure and reduction in systemic vascular resistance and diastolic blood pressure can be often seen even in case of subclinical hyperthyroidism. Thyrotoxicosis exacerbates the symptoms of a preexisting heart disease, but it can also cause complaints in case of a structurally normal heart. The most common cardiac complications are arrhythmias (mainly atrial fibrillation), heart failure and hypertension. Amiodarone is used for the treatment and prevention of several arrhythmias. It is safely applicable even in case of left ventricular dysfunction. The more common application is limited by its side effects that can develop even at low doses and may involve several organs (thyroid gland, lungs, liver, heart, nerve system among others). The complex effect of amiodarone on thyroid function ranges from mild abnormalities of thyroid function tests to overt thyrotoxicosis or hypothyroidism.

Amiodarone↗
PubMed2004

MS and NMR investigation of bioactive quinazolones.

To prepare effective PARP [poly(ADP)-ribose)polymerase-1] inhibitors, starting from 2-mercapto-4(3H)-quinazolone (1), several S-alkyl derivatives--2-alkylsulfanyl-3H-quinazolin-4-ones (2-5, 7-9)--as well as an S-benzyl derivative (10) were prepared using a simple alkylation method. Some of them are known compounds. Their structure was studied thoroughly by MS and NMR methods.

Magnetic Resonance Spectroscopy↗
PubMed2004

Experimental and quantum chemical studies of structure and reaction mechanisms of dioxouranium(VI) complexes in solution.

This perspective article describes the combination of experimental data and quantum chemical methods for the determination of structure and reaction mechanisms of uranyl(vi) complexes in aqueous solution. The first part assesses the accuracy of the chemical and thermodynamic properties of solvated uranyl(vi) complexes as obtained by various quantum chemical methods. The second part discusses structure determination, mechanisms for ligand exchange and the lability of coordinated water molecules for various uranyl(vi) complexes using a combination of NMR and quantum chemical data.

Journal Article↗
PubMed2004

Light therapy increases visual contrast sensitivity in seasonal affective disorder.

The purpose of this study was to investigate the effects of light therapy on visual contrast sensitivity in patients with seasonal affective disorder (n=10) and healthy control subjects (n=10). Static and dynamic visual contrast sensitivity was measured using a Venus system before and after 4 weeks of light therapy (10,000 lux, 30 min, 5 times a week). Light therapy increased static visual contrast sensitivity in the patients. We found no significant difference between the patients and controls either before or after light therapy. These results raise the possibility that light therapy induces retinal sensitization in seasonal affective disorder.

Adult↗
PubMed2004

Induction of arthritis in HLA-DR4-humanized and HLA-DQ8-humanized mice by human cartilage proteoglycan aggrecan but only in the presence of an appropriate (non-MHC) genetic background.

OBJECTIVE: To determine whether the rheumatoid arthritis (RA)-predisposing class II molecules of the major histocompatibility complex (MHC) can present cartilage proteoglycan (PG) aggrecan, and if so, to determine the epitope repertoire of the human cartilage PG in HLA-transgenic mice and determine whether HLA-transgenic mice develop arthritis in response to immunization with human cartilage PG. METHODS: Mice transgenic for HLA-DR2.Ab(0), DR3.Ab(0), DR4.Ab(0), and DQ8.Ab(0), lacking their own (mouse) class II antigens (Ab(0)), on the original (arthritis-resistant) and the arthritis-susceptible BALB/c backgrounds, were immunized with human cartilage PG. The T cell epitope repertoire presented by these class II MHC alleles was determined using a synthetic peptide library (143 peptides of the core protein of human cartilage PG), and arthritis development was monitored and compared in wild-type and HLA-transgenic/congenic BALB/c mice. RESULTS: Mice of the 4 HLA-transgenic lines, either on the original mixed, arthritis-resistant background or DR4.Ab(0)- and DQ8.Ab(0)-transgenic/congenic mice on the arthritis-susceptible BALB/c genetic background, responded well to PG immunization (as assessed by T cell responses and antibody and cytokine production), and a number of T cell epitopes along the core protein of human cartilage PG were identified. DR4.Ab(0)- and DQ8.Ab(0)-transgenic mice immunized with human cartilage PG developed arthritis, but only when these class II MHC molecules were present on the arthritis-susceptible (BALB/c) genetic background. CONCLUSION: A number of human cartilage PG epitopes can be presented by HLA alleles that predispose to the development of RA, but the epitopes of the cartilage PG presented by HLA-DR4 or HLA-DQ8 can induce arthritis only in the presence of an appropriate genetic (non-MHC) background.

Aggrecans↗
PubMed2004

The effect of bright light exposure on pupillary fluctuations in healthy subjects.

BACKGROUND: Light therapy is thought to be the first choice treatment of winter depression. However, its way of action is poorly understood. In order to find a solid effect of bright artificial light, we studied its possible alerting action through the spontaneous fluctuations of the pupil, considered to be an objective measurement of vigilance. METHODS: Pupillary fluctuations of 10 healthy subjects (mean age: 22+/-1 S.D. years) were measured for 60 s before and 15 min after 0.5 h, 10000-lux light exposure. The cumulative change in pupil size, characterised by the pupillary unrest index (PUI) decreased at each subject, and this decrease was in average 35+/-4.4% S.E.M. The average pupillary diameters were unchanged (101+/-2.2% S.E.M.). This analysis revealed that the slow components of the pupillary fluctuations also decreased considerably. LIMITATIONS: There was no dim light or other placebo control of the light treatment. CONCLUSIONS: Bright light exposure significantly influenced the pupillary fluctuations. We suppose that bright light exposure increases the level of alertness, and this could be a possible way by which bright artificial light exerts a beneficial effect also in affective disorders.

Adult↗