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Binding Potential (binding + potential)
Selected AbstractsStriatal dopamine D2 receptor availability in OCD with and without comorbid social anxiety disorder: preliminary findings,DEPRESSION AND ANXIETY, Issue 1 2008Franklin R. Schneier M.D. Abstract Dopamine D2 receptor availability in the striatum has been reported to be low in generalized social anxiety disorder (GSAD) and obsessive,compulsive disorder (OCD), but it has not been studied in persons with comorbid OCD and GSAD (OCD+GSAD). D2 receptor availability was assessed in 7 subjects with OCD+GSAD, 8 with OCD, and 7 matched healthy comparison (HC) subjects, all unmedicated adults. D2 receptor availability was assessed with single-photon emission computerized tomography (SPECT) to measure binding potential (BP) of the D2 receptor radiotracer [123I] iodobenzamide ([123I]IBZM). Mean striatal [123I]IBZM BP was significantly lower in the OCD+GSAD group (72.58 mL/g, SD=18.17) than in the HC group (118.41 mL/g, SD=45.40; P=.025). Mean BP in the OCD group (93.08 mL/g, SD=36.90) did not differ significantly from the HC group (P=.247). Trait detachment, as measured by the Detachment subscale of the Karolinska Scales of Personality, was negatively correlated with D2 availability across all subjects (rs=,.55, P=.013). Comorbid GSAD and OCD may be associated with decreased availability of D2 receptors in the striatum, consistent with prior findings in GSAD. Prior findings of decreased D2 receptor availability in noncomorbid OCD were not confirmed. Decreased D2 receptor availability was also associated with trait detachment, supporting prior findings in samples of healthy subjects. Depression and Anxiety 0:1,7, 2007. Published 2007 Wiley-Liss, Inc. [source] Increased antitumor potential of the raloxifene prodrug, raloxifene diphosphateINTERNATIONAL JOURNAL OF CANCER, Issue 9 2008Yoshinori Okamoto Abstract Raloxifene (RAL) significantly reduced the incidence of breast cancer in women at high risk of developing the disease. Unlike tamoxifen (TAM), an increased incidence of endometrial cancer was not observed in women treated with RAL. However, RAL, having two hydroxyl moieties, can be conjugated rapidly through phase II metabolism and excreted, making it difficult to achieve adequate bioavailability by oral administration in humans. As a result, higher doses must be administered to obtain an efficacy equivalent to that achieved with TAM. To improve oral bioavailability and antitumor potential, RAL diphosphate was prepared as a prodrug. RAL diphosphate showed several orders of magnitude lower binding potential to both ER, and ER, and weak antiproliferative potency on cultured human MCF-7 and ZR-75-1 breast cancer cells, as compared to RAL. However, RAL diphosphate has a much higher bioavailability than RAL, endowing it with higher antitumor potential than RAL against both 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma in rats and human MCF-7 breast cancer implanted in athymic nude mice. The RAL prodrug may provide greater clinical benefit for breast cancer therapy and prevention. © 2008 Wiley-Liss, Inc. [source] Binding characteristics and sensitivity to endogenous dopamine of [11C]-(+)-PHNO, a new agonist radiotracer for imaging the high-affinity state of D2 receptors in vivo using positron emission tomographyJOURNAL OF NEUROCHEMISTRY, Issue 4 2006Nathalie Ginovart Abstract [11C]-(+)-PHNO (4-propyl-9-hydroxynaphthoxazine) is a new agonist radioligand that provides a unique opportunity to measure the high-affinity states of the D2 receptors (D2 -high) using positron emission tomography (PET). Here we report on the distribution, displaceablity, specificity and modeling of [11C]-(+)-PHNO and compare it with the well characterized antagonist D2 radioligand, [11C]raclopride, in cat. [11C]-(+)-PHNO displayed high uptake in striatum with a mean striatal binding potential (BP) of 3.95 ± 0.85. Pre-treatment with specific D1 (SCH23390), D2 (raclopride, haloperidol) and D3 receptor (SB-277011) antagonists indicated that [11C]-(+)-PHNO binding in striatum is specific to D2 receptors. Within-subject comparisons showed that [11C]-(+)-PHNO BP in striatum was almost 2.5-fold higher than that measured with [11C]-(,)-NPA ([11C]-(,)-N-propyl-norapomorphine). Comparison of the dose-effect of amphetamine (0.1, 0.5 and 2 mg/kg; i.v.) showed that [11C]-(+)-PHNO was more sensitive to the dopamine releasing effect of amphetamine than [11C]raclopride. Amphetamine induced up to 83 ± 4% inhibition of [11C]-(+)-PHNO BP and only up to 56 ± 8% inhibition of [11C]raclopride BP. Scatchard analyses of [11C]-(+)-PHNO and [11C]raclopride bindings in two cats showed that the Bmax obtained with the agonist (29.6 and 32.9 pmol/mL) equalled that obtained with the antagonist (30.6 and 33.4 pmol/mL). The high penetration of [11C]-(+)-PHNO in brain, its high signal-to-noise ratio, its favorable in vivo kinetics and its high sensitivity to amphetamine shows that [11C]-(+)-PHNO has highly suitable characteristics for probing the D2 -high with PET. [source] Food and feed components for gut health-promoting adhesion of E. coli and Salmonella entericaJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 11 2008Petra M Becker Abstract BACKGROUND: A host runs less risk of contracting a gastrointestinal infection when enteropathogenic bacteria adhere to dietary fibers instead of to epithelial cell receptors. The aim of this study was to test the binding capacity of food and feed components for intestinal bacteria from various hosts using a miniaturized in vitro assay. In total, 18 dietary components were tested with four strains of E. coli, seven strains of Salmonella enterica and two strains of Lactobacillus. RESULTS: A comparison of the results obtained for all Salmonella strains tested revealed that konjac gum and sesame seed extract represented the most efficient binding matrices. Similarly, for all E. coli strains tested, sesame seed extract and artichoke performed well as binding matrices. Salmonella isolates from chickens adhered best to sesame seed extract. E. coli K88 and S. enterica sv. Typhimurium isolated from pigs effectively bound to BioMos®, pumpkin, sesame seed extract, and tomato. Sesame seed extract and tomato also had adhesive capacities for E. coli K 99, S. enterica sv. Dublin, and S. enterica sv. Typhimurium from calves. With human isolates, konjac gum showed a high binding potential for S. enterica and E. coli. CONCLUSION: The adhesion screening of different food and feed components resulted in highly discriminating product rankings. Copyright © 2008 Society of Chemical Industry [source] APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal agingANNALS OF NEUROLOGY, Issue 1 2010John C. Morris MD Objective To examine interactions of apolipoprotein E (APOE) genotype with age and with in vivo measures of preclinical Alzheimer disease (AD) in cognitively normal aging. Methods Two hundred forty-one cognitively normal individuals, aged 45,88 years, had cerebral amyloid imaging studies with Pittsburgh Compound-B (PIB). Of the 241 individuals, 168 (70%) also had cerebrospinal fluid (CSF) assays of amyloid-beta42 (A,42), tau, and phosphorylated tau (ptau181). All individuals were genotyped for APOE. Results The frequency of individuals with elevated mean cortical binding potential (MCBP) for PIB rose in an age-dependent manner from 0% at ages 45,49 years to 30.3% at 80,88 years. Reduced levels of CSF A,42 appeared to begin earlier (18.2% of those aged 45,49 years) and increase with age in higher frequencies (50% at age 80,88 years) than elevations of MCBP. There was a gene dose effect for the APOE4 genotype, with greater MCBP increases and greater reductions in CSF A,42 with increased numbers of APOE4 alleles. Individuals with an APOE2 allele had no increase in MCBP with age and had higher CSF A,42 levels than individuals without an APOE2 allele. There was no APOE4 or APOE2 effect on CSF tau or ptau181. Interpretation Increasing cerebral A, deposition with age is the pathobiological phenotype of APOE4. The biomarker sequence that detects A, deposition may first be lowered CSF A,42, followed by elevated MCBP for PIB. A substantial proportion of cognitively normal individuals have presumptive preclinical AD. ANN NEUROL 2010;67:122,131 [source] Serotonin 5HT1A receptor availability and pathological crying after strokeACTA NEUROLOGICA SCANDINAVICA, Issue 2 2007M. Møller Objectives,,, Post-stroke depression and pathological crying (PC) implicate an imbalance of serotonergic neurotransmission. We claim that PC follows serotonin depletion that raises the binding potential (pB) of the 5-HT1A receptor antagonist [carbonyl,11C]WAY-100635, which is reversible by selective serotonin re-uptake inhibitor (SSRI) treatment. Materials and Methods,,, We PET scanned patients with acute stroke and PC and age-matched control subjects. Maps of receptor availability were generated from the images of eight cortical regions and raphe nuclei. Results,,, The maps showed highest binding in limbic areas and raphe nuclei, while binding in basal ganglia and cerebellum was negligible. Baseline binding potentials of patients were lower than that of control subjects (3.7 ± 0.6 vs 4.2 ± 0.2). Treatment with SSRI markedly reduced free receptor sites, whereas placebo administration led to a global increase. Discussion,,, The study is the first suggestion of changes of serotonergic neurotransmission in the early phase of stroke and the modulation of these changes with SSRI treatment. [source] Substantial Thalamostriatal Dopaminergic Defect in Unverricht-Lundborg DiseaseEPILEPSIA, Issue 9 2007Miikka Korja Summary:,Purpose: Unverricht-Lundborg disease (ULD) is currently classified as progressive myoclonus epilepsy. Myoclonus, the characteristic symptom in ULD, suggests that dopamine neurotransmission may be involved in the pathophysiology of ULD. Our purpose was to examine brain dopaminergic function in ULD patients. Methods: Four genetically and clinically diagnosed ULD patients and eight healthy controls were scanned with [11C]raclopride-PET. PET images were coregistered to individual 1.5T MR images and region-of-interest analysis was performed for the striatum and thalamus. Standardized uptake values and individual voxel-wise binding potential maps of the patients and controls were also analyzed. Results: ULD patients had markedly higher (31,54%) dopamine D2-like receptor availabilities than healthy controls in both the striatum and the thalamus. The proportionally highest binding potentials were detected in the thalamus. There were no significant differences in the cerebellar uptake of [11C]raclopride in ULD patients versus healthy controls. Voxel-based results were in accordance with the region-of-interest analysis. Conclusions: These results suggest that dopaminergic modulation at the level of the striatum and thalamus could be a crucial factor contributing to the symptoms of ULD. In the light of our data, we propose that ULD with dopamine dysfunction and dyskinetic symptoms shares certain pathophysiological mechanisms with classical movement disorders. Future studies are therefore warranted to study the effect of dopaminergic pharmacotherapy in ULD. [source] Brain region binding of the D2/3 agonist [11C]-(+)-PHNO and the D2/3 antagonist [11C]raclopride in healthy humansHUMAN BRAIN MAPPING, Issue 4 2008Ariel Graff-Guerrero Abstract The D2 receptors exist in either the high- or low-affinity state with respect to agonists, and while agonists bind preferentially to the high-affinity state, antagonists do not distinguish between the two states. [11C]-(+)-PHNO is a PET D2agonist radioligand and therefore provides a preferential measure of the D2high receptors. In contrast, [11C]raclopride is an antagonist radioligand and thus binds with equal affinity to the D2 high- and low-affinity states. The aim was to compare the brain uptake, distribution and binding characteristics between [11C]-(+)-PHNO and [11C]raclopride in volunteers using a within-subject design. Both radioligands accumulated in brain areas rich in D2/D3 -receptors. However, [11C]-(+)-PHNO showed preferential uptake in the ventral striatum and globus pallidus, while [11C]raclopride showed preferential uptake in the dorsal striatum. Mean binding potentials were higher in the putamen (4.3 vs. 2.8) and caudate (3.4 vs 2.1) for [11C]raclopride, equal in the ventral-striatum (3.4 vs. 3.3), and higher in the globus pallidus for [11C]-(+)-PHNO (1.8 vs. 3.3). Moreover [11C]-(+)-PHNO kinetics in the globus pallidus showed a slower washout than other regions. One explanation for the preferential binding of [11C]-(+)-PHNO in the globus pallidus and ventral-striatum could be the presence of a greater proportion of high- vs. low-affinity receptors in these areas. Alternatively, the observed distribution could also be explained by a preferential binding of D3 -over-D2 with [11C]-(+)-PHNO. This differential binding of agonist vs. antagonist radioligand, especially in the critically important region of the limbic striatum/pallidum, offers new avenues to investigate the role of the dopamine system in health and disease. Hum Brain Mapp 2008. © 2007 Wiley-Liss, Inc. [source] Extrastriatal dopaminergic dysfunction in tourette syndromeANNALS OF NEUROLOGY, Issue 2 2010Thomas D. L. Steeves MD Objective Tourette syndrome (TS) is a neuropsychiatric disorder presenting with tics and a constellation of nonmotor symptoms that includes attention deficit hyperactivity disorder, obsessive,compulsive disorder, and impulse control disorders. Accumulated evidence from pharmacological trials and postmortem analyses suggests that abnormalities of dopaminergic neurotransmission play a key role in the pathogenesis of TS. A substantial body of evidence has also accrued to implicate regions outside the striatum in the generation of tics. Methods We initiated an [11C]FLB 457 positron emission tomography study in conjunction with an amphetamine challenge to evaluate extrastriatal dopamine (DA) D2/D3 receptor binding and DA release in a group of treatment-naive, adult TS patients compared with a group of age- and sex-matched controls. Results At baseline, TS patients showed decreased [11C]FLB 457 binding potentials bilaterally in cortical and subcortical regions outside the striatum, including the cingulate gyrus, middle and superior temporal gyrus, occipital cortex, insula, and thalamus. Amphetamine challenge induced DA release in both control and TS subjects bilaterally in many cortical regions; however, in TS patients, regions of increased DA release were significantly more widespread and extended more anteriorly to involve anterior cingulate and medial frontal gyri. Conversely, and in contrast to healthy controls, no significant DA release was noted in the thalami of TS patients. Interpretation These abnormalities of dopaminergic function localize to brain regions previously implicated in TS and suggest a mechanism for the hyperexcitability of thalamocortical circuits that has been documented in the disorder. ANN NEUROL 2010;67:170,181 [source] Serotonin 5HT1A receptor availability and pathological crying after strokeACTA NEUROLOGICA SCANDINAVICA, Issue 2 2007M. Møller Objectives,,, Post-stroke depression and pathological crying (PC) implicate an imbalance of serotonergic neurotransmission. We claim that PC follows serotonin depletion that raises the binding potential (pB) of the 5-HT1A receptor antagonist [carbonyl,11C]WAY-100635, which is reversible by selective serotonin re-uptake inhibitor (SSRI) treatment. Materials and Methods,,, We PET scanned patients with acute stroke and PC and age-matched control subjects. Maps of receptor availability were generated from the images of eight cortical regions and raphe nuclei. Results,,, The maps showed highest binding in limbic areas and raphe nuclei, while binding in basal ganglia and cerebellum was negligible. Baseline binding potentials of patients were lower than that of control subjects (3.7 ± 0.6 vs 4.2 ± 0.2). Treatment with SSRI markedly reduced free receptor sites, whereas placebo administration led to a global increase. Discussion,,, The study is the first suggestion of changes of serotonergic neurotransmission in the early phase of stroke and the modulation of these changes with SSRI treatment. 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