scholarly journals The Influence of Genetic Variants on Striatal Dopamine Transporter and D2 Receptor Binding after TB

2014 ◽  
Vol 34 (8) ◽  
pp. 1328-1339 ◽  
Author(s):  
Amy K Wagner ◽  
Joelle M Scanion ◽  
Carl R Becker ◽  
Anne C Ritter ◽  
Christian Niyonkuru ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Ventral Striatum ◽  
D2 Receptor ◽  
Variable Number ◽  
Small Sample ◽  
Post Injury ◽  
Positron Emission ◽  
Small Sample Sizes ◽  
Future Work

Dopamine (DA) neurotransmission influences cognition and recovery after traumatic brain injury (TBI). We explored whether functional genetic variants affecting the DA transporter (DAT) and D2 receptor (DRD2) impacted in vivo dopaminergic binding with positron emission tomography (PET) using [11C]βCFT and [11C]raclopride. We examined subjects with moderate/severe TBI ( N = 12) ~1 year post injury and similarly matched healthy controls ( N = 13). The variable number of tandem repeat polymorphism within the DAT gene and the Taql restriction fragment length polymorphism near the DRD2 gene were assessed. TBI subjects had age-adjusted DAT-binding reductions in the caudate, putamen, and ventral striatum, and modestly increased D2 binding in ventral striatum versus controls. Despite small sample sizes, multivariate analysis showed lower caudate and putamen DAT binding among DAT 9-allele carriers and DRD2 A2/A2 homozygotes with TBI versus controls with the same genotype. Among TBI subjects, 9-allele carriers had lower caudate and putamen binding than 10/10 homozygotes. This PET study suggests a hypodopaminergic environment and altered DRD2 autoreceptor DAT interactions that may influence DA transmission after TBI. Future work will relate these findings to cognitive performance; future studies are required to determine how DRD2/DAT1 genotype and DA-ligand binding are associated with neurostimulant response and TBI recovery.

scholarly journals Loss of D2 Receptor Binding with Age in Rhesus Monkeys: Importance of Correction for Differences in Striatal Size

1999 ◽  
Vol 19 (2) ◽  
pp. 218-229 ◽  
Author(s):  
Evan D. Morris ◽  
Svetlana I. Chefer ◽  
Mark A. Lane ◽  
Raymond F. Muzic ◽  
Dean F. Wong ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Rhesus Monkeys ◽  
Structural Changes ◽  
D2 Receptor ◽  
Binding Potential ◽  
Age Related ◽  
Positron Emission ◽  
Dopamine Receptor Binding

The relation between striatal dopamine D2 receptor binding and aging was investigated in rhesus monkeys with PET. Monkeys (n = 18, 39 to 360 months of age) were scanned with 11C-raclopride; binding potential in the striatum was estimated graphically. Because our magnetic resonance imaging analysis revealed a concomitant relation between size of striatum and age, the dynamic positron emission tomography (PET) data were corrected for possible partial volume (PV) artifacts before parameter estimation. The age-related decline in binding potential was 1% per year and was smaller than the apparent effect if the age-related change in size was ignored. This is the first in vivo demonstration of a decline in dopamine receptor binding in nonhuman primates. The rate of decline in binding potential is consistent with in vitro findings in monkeys but smaller than what has been measured previously in humans using PET. Previous PET studies in humans, however, have not corrected for PV error, although a decline in striatal size with age has been demonstrated. The results of this study suggest that PV correction must be applied to PET data to accurately detect small changes in receptor binding that may occur in parallel with structural changes in the brain.

scholarly journals The relationship between dose and serotonin transporter occupancy of antidepressants—a systematic review

2021 ◽  
Author(s):  
Anders Sørensen ◽  
Henricus G. Ruhé ◽  
Klaus Munkholm
Keyword(s):  
Serotonin Transporter ◽  
Antidepressant Treatment ◽  
Imaging Techniques ◽  
Small Sample ◽  
Short Treatment ◽  
Predicted Values ◽  
Small Sample Sizes ◽  
The Relationship ◽  
Short Treatment Duration

AbstractBrain imaging techniques enable the visualization of serotonin transporter (SERT) occupancy as a measure of the proportion of SERT blocked by an antidepressant at a given dose. We aimed to systematically review the evidence on the relationship between antidepressant dose and SERT occupancy. We searched PubMed and Embase (last search 20 May 2021) for human in vivo, within-subject PET, or SPECT studies measuring SERT occupancy at any dose of any antidepressant with highly selective radioligands ([11C]-DASB, [123I]-ADAM, and [11C]-MADAM). We summarized and visualized the dose-occupancy relationship for antidepressants across studies, overlaying the plots with a curve based on predicted values of a standard 2-parameter Michaelis–Menten model fitted using the observed data. We included seventeen studies of 10 different SSRIs, SNRIs, and serotonin modulators comprising a total of 294 participants, involving 309 unique occupancy measures. Overall, following the Michaelis–Menten equation, SERT occupancy increased with a higher dose in a hyperbolic relationship, with occupancy increasing rapidly at lower doses and reaching a plateau at approximately 80% at the usual minimum recommended dose. All the studies were small, only a few investigated the same antidepressant, dose, and brain region, and few reported information on factors that may influence SERT occupancy. The hyperbolic dose-occupancy relationship may provide mechanistic insight of relevance to the limited clinical benefit of dose-escalation in antidepressant treatment and the potential emergence of withdrawal symptoms. The evidence is limited by non-transparent reporting, lack of standardized methods, small sample sizes, and short treatment duration. Future studies should standardize the imaging and reporting procedures, measure occupancy at lower antidepressant doses, and investigate the moderators of the dose-occupancy relationship.

scholarly journals Comparative Evaluation of a Novel Concept Design Method

2013 ◽  
Author(s):  
Damian Rogers ◽  
Filippo A. Salustri
Keyword(s):  
Design Method ◽  
Statistical Significance ◽  
Small Sample ◽  
Design Methods ◽  
Concept Design ◽  
Sample Sizes ◽  
Pilot Experiment ◽  
Small Sample Sizes ◽  
Novel Concept ◽  
Future Work

Based on their previous work in creating a new method of design, termed the “Design by DNA” method, the authors are now experimentally validating the method against other, known methods. The goal of the experiment is to determine if Design by DNA promotes creative designs. Specifically, the authors are seeking to measure and compare creativity resulting from the use of Design by DNA and from other, known design methods. However, few have conducted empirical experiments in the past, and further, the literature on comparatively evaluating creativity of different design methods is relatively sparse. Therefore, the authors are developing a framework for defining and executing meaningful experiments that can accommodate various design methods, including Design by DNA, and also provide meaningful data to comparatively evaluate those methods, with the goal of determining whether Design by DNA impacts creativity in design. The experimental framework is described, and results of a pilot experiment are given. In that framework, creativity was characterized by novelty, usefulness, and cohesion. Due to small sample sizes, confidence in the results is not particularly high. Even so, some results do indicate several points of interest. An analysis of the results suggests that Design by DNA can offer advantages in engineering design, ranking higher in both the ‘usefulness’ and ‘cohesion’ categories of the creativity assessment. Hypotheses are given to explain why the experimental results show the slightly lower score in the ‘novelty’ category. Experiment participants were also evaluated on the NASA Task Loading Index (TLX) to evaluate how taxed they were using the different design methods and results are shown. Here, the Design by DNA method accrues better scores in 5 of the 6 NASA TLX categories, suggesting that it was less strenuous on the participants than the other methods. Statistical analysis of both the creativity scores and the TLX document shows confidence levels of between 65% and 96%, which is acceptable for very low populations. As this was a pilot experiment, the authors foresee future work to improve the results presented here. First, larger sample sizes are needed to improve statistical significance of our conclusions. Secondly, the authors wish to set out a series of experiments whereby each test is run by pitting one specific design method against the Design by DNA method, to better show a 1-on-1 comparison between the methods and highlight the strengths and weaknesses of each.

scholarly journals Monitoring internal contamination from OEW of an 18F-FDG production plant: WBC or head counting setup?

2019 ◽  
Vol 7 (3A) ◽  
Author(s):  
Bruno Melo Mendes ◽  
Bruno Machado Trindade ◽  
Telma Cristina Ferreira Fonseca ◽  
Tarcisio Passos Ribeiro de Campos
Keyword(s):  
Great Influence ◽  
Calibration Coefficient ◽  
Whole Body ◽  
Production Plant ◽  
Counting System ◽  
Internal Contamination ◽  
Positron Emission ◽  
18F Fdg ◽  
Future Work

The production 18F-FDG for positron emission tomography (PET) has consistently increased over the past two decades. The risk of internal contamination at 18F-FDG production facilities exists. A setup for evaluation of the 18F-FDG activity incorporated into the OEW brain, called Head Counting System (HCS), was presented in previous works. In this study, the whole body counter setup (WBC) was evaluated for monitoring 18F incorporations. The Monte Carlo Virtual Software (VMC in-vivo) and the MCNPx code were used to assess the system calibration coefficient (CC). Three 18F distributions were simulated: i) uniformly distributed in soft tissue (UDST); ii) Na18F biodistribution (NAFB); and iii) 18F-FDG biodistribution (FDGB). The calibration coefficient of WBC was compared to the current head counting system CC under the same biodistribution conditions. The ICRP male reference voxelized phantoms (RCP_AM) was used in the simulations. The results showed that the WBC setup was more efficient than the head counter for all the studied 18F distributions: UDST = 1060 %, FDGB = 488 % and NAFB = 340 %. Despite this, especially for 18F-FDG, the possibility of bladder voiding before measurement can lead to considerable uncertainties when the WBC setup is used.  On the other hand, bladder activity does not show great influence the calibration coefficient of the head counting system. Future work will evaluate the WBC sources of uncertainties in the measurement of 18F incorporated activity.

scholarly journals In vivo Serotonin-Sensitive Binding of [11C]CUMI-101: A Serotonin 1A Receptor Agonist Positron Emission Tomography Radiotracer

2010 ◽  
Vol 31 (1) ◽  
pp. 243-249 ◽  
Author(s):  
Matthew S Milak ◽  
Alin J Severance ◽  
Jaya Prabhakaran ◽  
JS Dileep Kumar ◽  
Vattoly J Majo ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Arterial Input Function ◽  
Input Function ◽  
Emission Tomography ◽  
Binding Potential ◽  
Papio Anubis ◽  
Positron Emission ◽  
Future Work ◽  
G Protein Coupled

Positron emission tomography studies of 5-hydroxytryptamine (5-HT)1A receptors have hitherto been limited to antagonist radiotracers. Antagonists do not distinguish high/low-affinity conformations of G protein-coupled receptors and are less likely to be sensitive to intrasynaptic serotonin levels. We developed a novel 5-HT1A agonist radiotracer [11C]CUMI-101. This study evaluates the sensitivity of [11C]CUMI-101 binding to increases in intrasynaptic serotonin induced by intravenous citalopram and fenfluramine. Two Papio anubis were scanned, using [11C]CUMI-101 intravenous bolus of 4.5±1.5 mCi. Binding potential (BPF= Bavail/ KD) was measured before ( n=10) and 20 minutes after elevation of intrasynaptic serotonin by intravenous citalopram (2 mg/kg, n=3; 4 mg/kg, n=3) and fenfluramine (2.5 mg/kg, n=3) using a metabolite-corrected arterial input function. Occupancy was also estimated by the Lassen graphical approach. Both citalopram and fenfluramine effects were significant for BPF ( P=0.031, P=0.049, respectively). The Lassen approach estimated 15.0, 30.4, and 23.7% average occupancy after citalopram 2 mg/kg, 4 mg/kg, and fenfluramine 2.5 mg/kg, respectively. [11C]CUMI-101 binding is sensitive to a large increase in intrasynaptic serotonin in response to robust pharmacological challenges. These modest changes in BPF may make it unlikely that this ligand will detect changes in intrasynaptic 5-HT under physiologic conditions; future work will focus on evaluating its utility in measuring the responsiveness of the 5-HT system to pharmacological challenges.

scholarly journals COVID-19 Infection-Related Coagulopathy and Viscoelastic Methods: A Paradigm for Their Clinical Utility in Critical Illness

Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 817 ◽  
Author(s):  
Argirios E. Tsantes ◽  
Andreas G. Tsantes ◽  
Styliani I. Kokoris ◽  
Stefanos Bonovas ◽  
Frantzeska Frantzeskaki ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Small Sample ◽  
Close Monitoring ◽  
Rotational Thromboelastometry ◽  
Coagulation Tests ◽  
Attractive Option ◽  
Small Sample Sizes ◽  
Fibrinolysis Shutdown ◽  
Insight Into

Hypercoagulability and thrombosis remain a challenge to diagnose and treat in severe COVID-19 infection. The ability of conventional global coagulation tests to accurately reflect in vivo hypo- or hypercoagulability is questioned. The currently available evidence suggests that markedly increased D-dimers can be used in identifying COVID-19 patients who may need intensive care unit (ICU) admission and close monitoring or not. Viscoelastic methods (VMs), like thromboelastography (TEG) and rotational thromboelastometry (ROTEM), estimate the dynamics of blood coagulation. The evaluation of coagulopathy by VMs in severe COVID-19 infection seems an increasingly attractive option. Available evidence supports that COVID-19 patients with acute respiratory failure suffer from severe hypercoagulability rather than consumptive coagulopathy often associated with fibrinolysis shutdown. However, the variability in definitions of both the procoagulant profile and the clinical outcome assessment, in parallel with the small sample sizes in most of these studies, do not allow the establishment of a clear association between the hypercoagulable state and thrombotic events. VMs can effectively provide insight into the pathophysiology of coagulopathy, detecting the presence of hypercoagulability in critically ill COVID-19 patients. However, it remains unknown whether the degree of coagulopathy can be used in order to predict the outcome, establish a diagnosis or guide anticoagulant therapy.

scholarly journals MicroRNAs as Salivary Markers for Periodontal Diseases: A New Diagnostic Approach?

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Gerhard Schmalz ◽  
Simin Li ◽  
Ralph Burkhardt ◽  
Sven Rinke ◽  
Felix Krause ◽  
...  
Keyword(s):  
Periodontal Diseases ◽  
Small Sample ◽  
In Vivo Studies ◽  
Case Definitions ◽  
Tissue Samples ◽  
Cancer Types ◽  
Small Sample Sizes ◽  
Noninvasive Markers

The aim of this review is to discuss current findings regarding the roles of miRNAs in periodontal diseases and the potential use of saliva as a diagnostic medium for corresponding miRNA investigations. For periodontal disease, investigations have been restricted to tissue samples and five miRNAs, that is, miR-142-3p, miR-146a, miR-155, miR-203, and miR-223, were repeatedly validated in vivo and in vitro by different validation methods. Particularly noticeable are the small sample sizes, different internal controls, and different case definitions of periodontitis in in vivo studies. Beside of that, the validated miRNAs are associated with inflammation and therefore with various diseases. Furthermore, several studies successfully explored the use of salivary miRNA species for the diagnosis of oral cancer. Different cancer types were investigated and heterogeneous methodology was used; moreover, no overlap of results was found. In conclusion, five miRNAs have consistently been reported for periodontitis; however, their disease specificity, detectability, and expression in saliva and their importance as noninvasive markers are questionable. In principle, a salivary miRNA diagnostic method seems feasible. However, standardized criteria and protocols for preanalytics, measurements, and analysis should be established to obtain comparable results across different studies.

Dementia praecox redux: A systematic review of the nicotinic receptor as a target for cognitive symptoms of schizophrenia

2015 ◽  
Vol 29 (2) ◽  
pp. 197-211 ◽  
Author(s):  
Arann R Rowe ◽  
Louise Mercer ◽  
Valentina Casetti ◽  
Kyra-Verena Sendt ◽  
Giovanni Giaroli ◽  
...  
Keyword(s):  
Small Sample ◽  
Cognitive Test ◽  
Allosteric Modulators ◽  
Self Medication ◽  
Attentional Processing ◽  
Pharmacological Agents ◽  
Negative Findings ◽  
Study Methodology ◽  
Small Sample Sizes ◽  
Future Work

Most individuals with schizophrenia suffer some cognitive dysfunction: such deficits are predictive of longer-term functioning; and current dopamine-blocking antipsychotics have made little impact on this domain. There is a pressing need to develop novel pharmacological agents to tackle this insidious but most disabling of problems. The acetylcholinergic system is involved in cognitive and attentional processing, and its metabotropic and nicotinic receptors are widespread throughout the brain. Deficits in acetylcholinergic functioning occur in schizophrenia, and high rates of tobacco smoking have been posited to represent a form of self-medication. The nicotinic acetylcholine receptor (nAChR) has emerged as a putative target to improve cognitive deficits in schizophrenia, and this study systematically reviewed the emerging data. Nineteen studies were identified, covering three compound classes: agonists at the α7 and α 4β2 nAChRs, and positive allosteric modulators. Overall data are underwhelming: some studies showed significant improvements in cognition but as many studies had negative findings. It remains unclear if this represents drug limitations or nascent study methodology problems. The literature is particularly hindered by variability in inclusion of smokers, generally small sample sizes, and a lack of consensus on cognitive test batteries. Future work should evaluate longer-term outcomes, and, particularly, the effects of concomitant cognitive training.

The Use of DCE-MRI to Evaluate the Blood Supply to the Nipple-Areola Complex: A Study in 245 Asian Women

2021 ◽  
Vol 41 (6) ◽  
pp. NP346-NP354
Author(s):  
Dawei Wang ◽  
Shixuan Xiong ◽  
Tao Ai ◽  
Ning Zeng ◽  
Yuping Ren ◽  
...  
Keyword(s):  
Blood Supply ◽  
Maximum Intensity Projection ◽  
Small Sample ◽  
Asian Women ◽  
Dce Mri ◽  
Nipple Areola Complex ◽  
Areola Complex ◽  
Breast Plastic Surgery ◽  
Small Sample Sizes

Abstract Background Understanding the main blood supply to the nipple-areola complex (NAC) is important for breast plastic surgery. However, previous reports have involved studies of cadavers and small sample sizes. Objectives This study aimed to identify and classify the in vivo blood supply to the NAC based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Methods DCE-MRI images of 393 breasts in 245 Asian women obtained from March 2012 to October 2019 were included retrospectively. Axial, coronal, and sagittal maximum-intensity projection images were evaluated to identify all vessels supplying the NAC. Blood supply to the NAC was classified into 9 anatomic zones: superomedial (Ia), medial (Ib), inferomedial (Ic), superolateral (IIa), lateral (IIb), inferolateral (IIc), central (III), inferior (IV), and superior (V). Results A total of 637 source vessels were identified in 393 breasts. Of the 393 breasts, 211 (53.7%) were supplied by a single zone, 132 (33.6%) by 2 zones, 38 (9.7%) by 3 zones, and 12 (3.1%) by 4 zones. Of the 637 vessels, 269 (42.2%) vessels were in zone Ia, 180 (28.3%) vessels were in zone IIa, and <10% of vessels were in the other zones. The number of NAC perfusion zones (P = 0.093) and the distribution of source vessels (P = 0.602) did not differ significantly between the left and right breasts. Conclusions DCE-MRI provides a clear indication of the blood supply to the NAC. Blood vessels from the superomedial and superolateral zones were the predominant sources of blood supplying the NAC.

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