α-[11C] methyl-L tryptophan-PET as a surrogate for interictal cerebral serotonin synthesis in migraine without aura

Cephalalgia ◽  
2013 ◽  
Vol 34 (3) ◽  
pp. 165-173 ◽  
Author(s):  
Y Sakai ◽  
M Nishikawa ◽  
M Diksic ◽  
M Aubé
Keyword(s):  
Migraine Without Aura ◽  
Surrogate Marker ◽  
Three Dimensions ◽  
Control Subjects ◽  
Positron Emission ◽  
Before And After ◽  
Regulation Mechanisms ◽  
Migraine Group ◽  
And Control

Background Alteration in central serotonin biology has been implicated in migraine, and serotonin (5-HT) agonists have been available for more than a decade in the treatment of that condition. Objectives To test this hypothesis, we studied in vivo using positron-emission tomography (PET) and α-[11C] methyl-L-tryptophan (α-[11C]MTrp) as a surrogate marker of cerebral 5-HT synthetic rate before and after administration of eletriptan in migraine and control subjects. Methods Six nonmenopausal female migraine subjects with migraine without aura (MoA) and six nonmenopausal age-matched female control subjects were scanned at baseline and after oral administration of 40 mg of eletriptan. Migraine subjects at the time of PET had to have been headache free for a minimum of three days. Images of (α-[11C]MTrp) brain trapping were colocalized with individual MRI images in three dimensions and analyzed. Results There was no difference in baseline cerebral global 5-HT synthesis between migraine and control subjects. After administration of eletriptan, there was a striking global reduction in cerebral 5-HT synthesis (K*) in the migraine group and in 22 regions of interest (ROIs). In control subjects, no significant changes were found in global cerebral 5-HT synthesis (K*) or in any of the ROIs. Conclusions These findings suggest in migraine an interictal alteration in the regulation mechanisms of cerebral 5-HT synthesis.

Porphyrin-lipid nanovesicles (Porphysomes) are effective photosensitizers for photodynamic therapy

Nanophotonics ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Keegan Guidolin ◽  
Lili Ding ◽  
Juan Chen ◽  
Brian C. Wilson ◽  
Gang Zheng
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Growth ◽  
Intrinsic Structure ◽  
Therapeutic Applications ◽  
Positron Emission ◽  
Theranostic Agents ◽  
Negative Controls ◽  
And Control ◽  
Complete Tumor

Abstract Porphysomes (PS) are liposome-like nanoparticles comprising pyropheophorbide-conjugated phospholipids that have demonstrated potential as multimodal theranostic agents for applications that include phototherapies, targeted drug delivery and in vivo fluorescence, photoacoustic, magnetic resonance or positron emission imaging. Previous therapeutic applications focused primarily on photothermal therapy (PTT) and suggested that PSs require target-triggered activation for use as photodynamic therapy (PDT) sensitizers. Here, athymic nude mice bearing subcutaneous A549 human lung tumors were randomized into treatment and control groups: PS-PDT at various doses, PS-only and no treatment negative controls, as well as positive controls using the clinical photosensitizer Photofrin. Animals were followed for 30 days post-treatment. PS-PDT at all doses demonstrated a significant tumor ablative effect, with the greatest effect seen with 10 mg/kg PS at a drug-light interval of 24 h. By comparison, negative controls (PS-only, Photofrin-only, and no treatment) showed uncontrolled tumor growth. PDT with Photofrin at 5 mg/kg and PS at 10 mg/kg demonstrated similar tumor growth suppression and complete tumor response rates (15 vs. 25%, p = 0.52). Hence, porphysome nanoparticles are an effective PDT agent and have the additional advantages of multimodal diagnostic and therapeutic applications arising from their intrinsic structure. Porphysomes may also be the first single all-organic agent capable of concurrent PDT and PTT.

SECRETION OF DIHYDROTESTOSTERONE BY HUMAN PROSTATE IN BENIGN PROSTATIC HYPERTROPHY

1974 ◽  
Vol 77 (2) ◽  
pp. 401-407 ◽  
Author(s):  
J. A. Mahoudeau ◽  
A. Delassalle ◽  
H. Bricaire
Keyword(s):  
Plasma Levels ◽  
Benign Prostatic Hypertrophy ◽  
Prostatic Hypertrophy ◽  
Human Prostate ◽  
Control Subjects ◽  
Peripheral Plasma ◽  
Significant Difference ◽  
Before And After ◽  
The Mean ◽  
And Control

ABSTRACT Plasma levels of testosterone (T) and 5α-dihydrotestosterone (DHT) were determined by radioimmunoassay in 29 patients with benign prostatic hypertrophy (BPH) and in 56 control men of various ages. No significant difference was found in T, DHT nor DHT/T ratio between BPH and control subjects of similar age. Plasma DHT was higher in the prostatic than in the peripheral veins in 8/9 patients with BPH during laparotomy, indicating a prostatic secretion of DHT. No difference in the mean T nor the mean DHT was found in peripheral plasma before and after adenomectomy.

Abstract 11863: Enhanced Adventitial Vasa Vasorum Formation in Patients With Vasospastic Angina -Assessment With Optical Frequency Domain Imaging-

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Kensuke Nishimiya ◽  
Yasuharu Matsumoto ◽  
Jun Takahashi ◽  
Takeshi Kato ◽  
Kazuma Oyama ◽  
...  
Keyword(s):  
Frequency Domain ◽  
Coronary Spasm ◽  
Vasa Vasorum ◽  
Vasospastic Angina ◽  
Optical Frequency ◽  
Cardiovascular Risks ◽  
Optical Frequency Domain Imaging ◽  
Control Subjects ◽  
And Control

Background: We have previously demonstrated that adventitial inflammation, including enhanced formation of adventitial vasa vasorum (VV), is involved in the pathogenesis of coronary spasm in porcine models and that optical frequency domain imaging (OFDI) allows us to visualize adventitial VV in humans in vivo. However, it remains to be elucidated whether adventitial VV is also involved in the coronary hyperconstriction in patients with vasospastic angina (VSA). In this study, we thus examined the extent of VV formation in VSA patients and control subjects by using OFDI. Methods: OFDI image acquisition of the left anterior descending coronary artery (LAD) was performed along the LAD at every 10 mm length after intracoronary administration of isosorbide dinitrate in 21 patients with acetylcholine-induced spasm and 10 control subjects without the spasm. Results: Patient characteristics were comparable between VSA patients and control subjects, including sex, age, cardiovascular risks and medications. OFDI and reconstructed 3D-OFDI images clearly visualized enhanced VV formation in VSA patients as compared with control subjects (Figure). Quantitative analysis showed that VV area was significantly larger in VSA patients than in control subjects (VSA, 0.093±0.006 vs. control, 0.040±0.006 mm 2 , P<0.0001), whereas vessel diameter, wall thickness and coronary lesion types were all comparable between the 2 groups. Conclusions: These results demonstrate for the first time that adventitial VV formation is enhanced at the spastic coronary segment in VSA patients, suggesting the important role of adventitial VV in the pathogenesis of coronary spasm.

scholarly journals Glucocorticoid-induced eosinopenia results from CXCR4-dependent bone marrow migration

Blood ◽  
2020 ◽  
Vol 136 (23) ◽  
pp. 2667-2678
Author(s):  
So Gun Hong ◽  
Noriko Sato ◽  
Fanny Legrand ◽  
Manasi Gadkari ◽  
Michelle Makiya ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Rhesus Macaques ◽  
Human Study ◽  
Isolation Technique ◽  
Selective Blockade ◽  
First Line Therapy ◽  
Positron Emission ◽  
Before And After ◽  
Eosinophilic Disorders

Abstract Glucocorticoids are considered first-line therapy in a variety of eosinophilic disorders. They lead to a transient, profound decrease in circulating human eosinophils within hours of administration. The phenomenon of glucocorticoid-induced eosinopenia has been the basis for the use of glucocorticoids in eosinophilic disorders, and it has intrigued clinicians for 7 decades, yet its mechanism remains unexplained. To investigate, we first studied the response of circulating eosinophils to in vivo glucocorticoid administration in 3 species and found that the response in rhesus macaques, but not in mice, closely resembled that in humans. We then developed an isolation technique to purify rhesus macaque eosinophils from peripheral blood and performed live tracking of zirconium-89-oxine–labeled eosinophils by serial positron emission tomography/computed tomography imaging, before and after administration of glucocorticoids. Glucocorticoids induced rapid bone marrow homing of eosinophils. The kinetics of glucocorticoid-induced eosinopenia and bone marrow migration were consistent with those of the induction of the glucocorticoid-responsive chemokine receptor CXCR4, and selective blockade of CXCR4 reduced or eliminated the early glucocorticoid-induced reduction in blood eosinophils. Our results indicate that glucocorticoid-induced eosinopenia results from CXCR4-dependent migration of eosinophils to the bone marrow. These findings provide insight into the mechanism of action of glucocorticoids in eosinophilic disorders, with implications for the study of glucocorticoid resistance and the development of more targeted therapies. The human study was registered at ClinicalTrials.gov as #NCT02798523.

Polymer-Encapsulated PC-12 Cells Demonstrate High-Affinity Uptake of Dopamine in Vitro and 18F-DOPA Uptake and Metabolism after Intracerebral Implantation in Nonhuman Primates

1997 ◽  
Vol 6 (5) ◽  
pp. 469-477 ◽  
Author(s):  
Thyagarajan Subramanian ◽  
Dwaine F. Emerich ◽  
Roy A. E. Bakay ◽  
John M. Hoffman ◽  
Mark M. Goodman ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pc 12 Cells ◽  
In Vivo Experiments ◽  
Positron Emission ◽  
Before And After ◽  
Uptake And Metabolism ◽  
Dopa Uptake

Intracranial implantation of polymer-encapsulated PC-12 cells has been shown to improve motor behavioral performance in animal models of Parkinson's disease. The purpose of this blinded study was to examine whether such improvement is associated with the active uptake and metabolism of dopamine precursors by intracerebrally implanted polymer-encapsulated PC-12 cells. In an in vitro experiment we demonstrate that 3H-dopamine uptake by PC-12 cells was 108 fmol/min × 106 cells, and that this uptake can be specifically blocked 88% by the addition of 10 nM of nomifensine. In the in vivo experiments, polymer-encapsulated PC-12 cells were implanted in four MPTP-treated monkeys into the left deep parietal white matter (R1) or left striatum (R2-4). A fifth MPTP-treated monkey (R5) served as a control and received left striatal implants of empty capsules. 18F-Dopa Positron Emission Tomography (PET) imaging was performed on each monkey before and after implantation surgery by blinded investigators. PET images obtained 5-13 wk after implantation demonstrated well delineated focal areas of high 18F-dopa uptake in R1, R2, and R4. The focal area of high 18F-dopa uptake in R1 precisely coregistered on a brain magnetic resonance image to the site of implantation. R3 (in whom the polymer-encapsulated PC-12 cells demonstrated poor cell survival upon explantation) and R5 (empty capsules) failed to demonstrate any area of increased 18F-dopa uptake in their PET images. Histological examination of the host brain revealed no sprouting of dopaminergic nerve terminals around the implantation sites of the polymer-encapsulated PC-12 cells. These results indicate that the previously noted behavioral improvement after intrastriatal implantation of polymer encapsulated PC-12 cells is at least in part due to their highly specific uptake and metabolism of dopamine precursors. Furthermore, these data suggest that polymer-encapsulated PC-12 cells can store, reuptake, and functionally replenish dopamine and therefore, may be an effective treatment for Parkinson's disease.

scholarly journals Measurement of Changes in Opioid Receptor Binding in Vivo During Trigeminal Neuralgic Pain Using [11C]Diprenorphine and Positron Emission Tomography

1999 ◽  
Vol 19 (7) ◽  
pp. 803-808 ◽  
Author(s):  
Anthony K. P. Jones ◽  
Niel D. Kitchen ◽  
Hiroshi Watabe ◽  
Vincent J. Cunningham ◽  
Terry Jones ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Volume Of Distribution ◽  
Emission Tomography ◽  
Subcortical Structures ◽  
Endogenous Opioid ◽  
Positron Emission ◽  
Before And After ◽  
Pain State ◽  
Parietal Cortices

The binding of [11C]diprenorphine to µ, κ, and Δ subsites in cortical and subcortical structures was measured by positron emission tomography in vivo in six patients before and after surgical relief of trigeminal neuralgia pain. The volume of distribution of [11C]diprenorphine binding was significantly increased after thermocoagulation of the relevant trigeminal division in the following areas: prefrontal, insular, perigenual, mid-cingulate and inferior parietal cortices, basal ganglia, and thalamus bilaterally. In addition to the pain relief associated with the surgical procedure, there also was an improvement in anxiety and depression scores. In the context of other studies, these changes in binding most likely resulted from the change in the pain state. The results suggest an increased occupancy by endogenous opioid peptides during trigeminal pain but cannot exclude coexistent down-regulation of binding sites.

Women and Chocolate Advertising: Exposure to Thin Models Exacerbates Ambivalence

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1 ◽  
Author(s):  
K. Durkin ◽  
K. Rae
Keyword(s):  
Three Dimensions ◽  
Exposure Condition ◽  
Approach And Avoidance ◽  
Different Types ◽  
Before And After ◽  
Advertising Exposure ◽  
And Control ◽  
Disordered Eating Patterns ◽  
The Impact ◽  
General Community

Chocolate craving is very common among women. It is known to be associated with ambivalent attitudes and with eating disorders.Aims:The present study investigated the impact of different types of media images (associating the product with thin versus overweight models) on females’ attitudes to chocolate.Method:Eighty-four female participants were recruited from the general community. Age ranged from 17 to 63 years (mean=35). Mean BMI was 23.4. Participants were allocated randomly to one of three conditions: Chocolate with thin models, Chocolate with overweight models, and Control (non-chocolate related products). Groups did not differ on age and BMI. They were assessed before and after exposure using the Orientation to Chocolate Questionnaire, which measures three dimensions of chocolate craving: guilt, approach and avoidance.Results:Participants in the thin exposure condition experienced more guilt and were more likely to report both heightened approach and avoidance of chocolate after exposure. In contrast, participants in the overweight exposure condition had lower guilt and lower approach to chocolate, with no change in avoidance, after exposure. No changes were obtained for the females in the control condition.Conclusion:These findings suggest that viewing thin images in association with chocolate intensifies women's ambivalence towards the product. It is argued that ambivalence is stressful and fosters disordered eating patterns.

Prefrontal cortex activity in people with schizophrenia and control subjects

1998 ◽  
Vol 172 (4) ◽  
pp. 316-323 ◽  
Author(s):  
Sean A. Spence ◽  
Steven R. Hirsch ◽  
David J. Brooks ◽  
Paul M. Grasby
Keyword(s):  
Prefrontal Cortex ◽  
Dorsolateral Prefrontal Cortex ◽  
Symptomatic Improvement ◽  
Emission Tomography ◽  
Cortical Function ◽  
Control Subjects ◽  
Prefrontal Cortical ◽  
Positron Emission ◽  
Dorsolateral Prefrontal ◽  
And Control

BackgroundHypo-activation of the left dorsolateral prefrontal cortex is inconsistently found in neuroimaging studies of schizophrenia. As the left dorsolateral prefrontal cortex is involved in the generation of action, disordered function in this region may be implicated in schizophrenic symptomatology.MethodWe used H215O positron emission tomography to study dorsolateral prefrontal cortical function in men with schizophrenia (n=13) and male control subjects (n=6) performing joystick movements on two occasions, 4–6 weeks apart. The patients were initially in relapse. To clarify dorsolateral prefrontal cortical function we also scanned another group of control subjects (n=5) performing mouth movements.ResultsThe control subjects performing hand or mouth movements activated the left dorsolateral prefrontal cortex to a maximum when the movements were self-selected. The men with relapsed schizophrenia exhibited left dorsolateral prefrontal cortical hypo-activation, which remitted with symptomatic improvement.ConclusionsHypofrontality in these patients is a dynamic phenomenon across time, possibly related to current symptomatology. The most appropriate question about the presence of hypofrontality in schizophrenia may be when, rather than whether, it will occur.

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