Biomedical subjects

Zsolt Szabo

Publications and source records attributed to Zsolt Szabo.

5 recordsLinked to original sources

PubMed2003

Positron emission tomography of striatal serotonin transporters in Parkinson disease.

BACKGROUND: Little is known about serotonin neurons in Parkinson disease (PD). OBJECTIVE: To study the serotonin system in PD with positron emission tomography, using the serotonin transporter radioligand [11C](+)McN5652. DESIGN AND PATIENTS: We measured the density of the serotonin transporter and the density of [11C]WIN35,428-labeled dopamine transporters in the striatum of 13 adults with PD and 13 age- and sex-matched controls. To assess the effects of possible differences in blood flow or brain atrophy, we also measured regional cerebral blood flow and the size of the regions of interest for the caudate nucleus and putamen. RESULTS: Patients with PD showed reductions in the specific distribution volumes of [11C](+)McN5652 in the caudate (P<.01) and putamen (P<.01), along with the expected reductions in striatal [11C]WIN35,428 binding (P<.01). There were no reductions in regional cerebral blood flow or the sizes of the regions of interest, mitigating against potential confounding effects of blood flow, brain atrophy, or partial volume effects. Reductions in serotonin transporter binding correlated with ratings of disease staging. CONCLUSIONS: These results suggest that the density of serotonin transporters, like that of dopamine transporters, is reduced in the striatum of patients with PD and that these changes are related to disease stage.

Adult↗

PubMed2002

Modified regression model for the Logan plot.

Logan's graphical model is a robust estimation of the total distribution volume (DVt) of reversibly bound radiopharmaceuticals, but the resulting DVt values decrease with increasing noise. The authors hypothesized that the noise dependence can be reduced by a linear regression model that minimizes the sum of squared perpendicular rather than vertical (y) distances between the data points and fitted straight line. To test the new method, 15 levels of simulated noise (repeated 2,000 times) were added to synthetic tissue activity curves, calculated from two different sets of kinetic parameters. Contrary to the traditional method, there was no ( P > 0.05) or dramatically decreased noise dependence with the perpendicular model. Real dynamic 11C (+) McN5652 serotonin transporter binding data were processed either by applying Logan analysis to average counts of large areas or by averaging the Logan slopes of individual-voxel data. There were no significant differences between the parameters when the perpendicular regression method was used with both approaches. The presented experiments show that the DVt calculated from the Logan plot is much less noise dependent if the linear regression model accounts for errors in both the x and y variables, allowing fast creation of unbiased parametric images from dynamic positron-emission tomography studies.

Artifacts↗

PubMed2002

Hormone responses to citalopram in abstinent alcohol dependent subjects.

BACKGROUND: The integrity of serotonin neurotransmission may be important in reducing risk for alcoholism and in preventing relapse to alcohol dependence. There are several lines of evidence suggesting that alcohol dependent persons have an altered and/or injured serotonin system. The purpose of this study was to examine ACTH, cortisol, and prolactin responses to the selective serotonin reuptake inhibitor (SSRI), citalopram, as a function of personal or family history of alcohol dependence in a group of abstinent alcohol dependent men. METHODS: Twelve healthy, abstinent male participants who met diagnostic criteria for a history of alcohol dependence but not for other Axis I disorders were included in the study (mean years abstinent, 3.5 +/- 3.7; mean years of dependent drinking, 15.2 +/- 6.9). Fourteen healthy volunteers served as control subjects. Controls did not meet the DSM-IV diagnostic criteria for any Axis I disorders and history of drug or alcohol abuse or dependence. All subjects were also characterized by the presence or absence of family history of alcoholism validated by collateral interviews. RESULTS: ACTH responses to citalopram were minimally faster in abstinent alcohol dependent men compared to controls. However, cortisol and prolactin responses to citalopram did not differ by personal or family history of alcohol dependence. There was no correlation between hormone responses and the duration of abstinence from alcohol; between hormone responses and the years of dependent drinking and between hormone responses and NEO Personality Inventory scores. CONCLUSION: By probing the functional capacity of the serotonin system with citalopram, we did not detect physiologically relevant hormone differences between abstinent alcohol dependent men and controls.

Adrenocorticotropic Hormone↗

PubMed2002

Comparison of (+)-(11)C-McN5652 and (11)C-DASB as serotonin transporter radioligands under various experimental conditions.

UNLABELLED: There has been considerable interest in the development of a PET radioligand selective for the serotonin (5-hydroxytryptamine [5-HT]) transporter (SERT) that can be used to image 5-HT neurons in the living human brain. The most widely used SERT radiotracer to date, trans-1,2,3,5,6,10-beta-hexahydro-6-[4-(methylthio)phenyl[pyrrolo-[2,1-a]isoquinoline ((+)-(11)C-McN5652), has been successful in this regard but may have some limitations. Recently, another promising SERT radiotracer, 3-(11)C-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile ((11)C-DASB), has been described. The purpose of this study was to compare and contrast (+)-(11)C-McN5652 and (11)C-DASB under various experimental conditions. METHODS: Radioligand comparisons were performed in a control baboon, a baboon with reduced SERT density ((+/-)-3,4-methylenedioxymethamphetamine [MDMA] lesion), and a baboon with reduced SERT availability (paroxetine pretreatment). Under each of these experimental conditions, repeated (triplicate) PET studies were performed with each ligand. RESULTS: Both radiotracers bound preferentially in brain regions known to contain high SERT density. For both ligands, there was a high correlation between the amount of regional brain ligand binding and the known regional brain concentration of SERT. Binding of both ligands was decreased after MDMA neurotoxicity (reduced SERT density), and (+)-(11)C-McN5652 and (11)C-DASB were comparably effective in detecting reduced SERT density after MDMA-induced 5-HT neurotoxicity. Pretreatment with paroxetine dramatically altered the metabolism and kinetics of both tracers and appeared to displace both ligands primarily from regions with high SERT density. Compared with (+)-(11)C-McN5652, (11)C-DASB had higher brain activity and a faster washout rate and provided greater contrast between subcortical and cortical brain regions. CONCLUSION: (11)C-DASB and (+)-(11)C-McN5652 are suitable as PET ligands of the SERT and for detecting MDMA-induced 5-HT neurotoxicity. (11)C-DASB may offer some advantages. Additional studies are needed to further characterize the properties and capabilities of both ligands in health and disease.

Aniline Compounds↗

PubMed2001

Use of positron emission tomography to study AT1 receptor regulation in vivo.

Increased sodium intake and enhanced sodium sensitivity are implicated in the pathogenesis of hypertension and in the control of a major regulator of BP, the type 1 angiotensin receptor (AT(1) receptor). An in vivo technique to study changes of renal AT(1) receptors by dietary sodium was developed that uses positron emission tomography (PET). PET revealed that renal cortical AT(1) receptor binding was increased in sodium-loaded compared with sodium-deprived dogs, which correlated with ex vivo estimations of AT(1) receptor numbers. Plasma renin activity, angiotensin II, and aldosterone were inversely related to changes in AT(1) receptor binding. These results demonstrate, for the first time in vivo, that the renal AT(1) receptor is inversely related to the activity of the renin angiotensin system, which may provide a compensatory mechanism to prevent inappropriate fluctuations in arterial BP. The ability to measure AT(1) receptor binding in vivo has potential significance for clinical studies of AT(1) receptors, because PET is a noninvasive imaging technique that is readily applicable in humans.

Aldosterone↗