scholarly journals High uptake of 68Ga-PSMA-HBED-CC and 18F-DCFPyL in the peritumoral area of rat gliomas due to activated astrocytes

2020 ◽  
Author(s):  
Dennis Oliveira ◽  
Carina Stegmayr ◽  
Alexander Heinzel ◽  
Johannes Ermert ◽  
Bernd Neumaier ◽  
...  

Abstract Background Recent studies reported on high uptake of the PSMA ligands [68Ga]HBED-CC (68Ga-PSMA) and 18F-DCFPyL in cerebral gliomas. This study explores the regional uptake and cellular targets of 68Ga-PSMA and 18F-DCFPyL in three different rat glioma models.Methods F98, 9L or U87 rat gliomas were implanted into the brains of 38 rats. After 13 days of tumor growth, 68Ga-PSMA (n=21) or 18F-DCFPyL (n=17) were injected intravenously and animals were sacrificed 40 min later. Cryosections of the tumor bearing brains were analyzed by ex vivo autoradiography and immunofluorescence staining for blood vessels, microglia, astrocytes and presence of PSMA. Blood-brain barrier (BBB) permeability was tested by coinjection of Evans blue dye (EBD). 68Ga-PSMA uptake after restoration of BBB integrity by treatment with dexamethasone (Dex) was evaluated in four animals with U87 gliomas. Competition experiments using the PSMA-receptor inhibitor 2-(Phosphonomethyl)pentane-1,5-dioic acid (PMPA) were performed for both tracers in two animals each.Results All tumors showed a strong 68Ga-PSMA and 18F-DCFPyL binding in the peritumoral area and moderate binding in the center of the tumors. PMPA administration led to complete inhibition of 68Ga-PSMA and 18F-DCFPyL binding in the peritumoral region. Restoration of BBB by Dex treatment reduced EBD extravasation but 68Ga-PSMA binding remained unchanged. Expression of activated microglia (CD11b) was low in the intra- and peritumoral area but GFAP staining revealed strong activation of astrocytes in congruency to the tracer binding in the peritumoral area. Conclusions High uptake of 68Ga-PSMA and 18F-DCFPyL in the peritumoral area of all glioma models is presumably caused by activated astrocytes. This may represent a limitation for the clinical application of PSMA ligands in gliomas. BBB permeability had a minor influence on tracer binding.

2020 ◽  
Author(s):  
Dennis Oliveira ◽  
Carina Stegmayr ◽  
Alexander Heinzel ◽  
Johannes Ermert ◽  
Bernd Neumaier ◽  
...  

Abstract Background Recent studies reported on high uptake of the PSMA ligands [ 68 Ga]HBED-CC ( 68 Ga-PSMA) and 18 F-DCFPyL in cerebral gliomas. This study explores the regional uptake and cellular targets of 68 Ga-PSMA and 18 F-DCFPyL in three different rat glioma models. Methods F98, 9L or U87 rat gliomas were implanted into the brains of 38 rats. After 13 days of tumor growth, 68 Ga-PSMA (n=21) or 18 F-DCFPyL (n=17) were injected intravenously and animals were sacrificed 40 min later. Five animals for each tracer and tumor model were additionally investigated by micro-PET at 20-40 min postinjection. Cryosections of the tumor bearing brains were analyzed by ex vivo autoradiography and immunofluorescence staining for blood vessels, microglia, astrocytes and presence of PSMA. Blood-brain barrier (BBB) permeability was tested by coinjection of Evans blue dye (EBD). 68 Ga-PSMA uptake after restoration of BBB integrity by treatment with dexamethasone (Dex) was evaluated in four animals with U87 gliomas. Competition experiments using the PSMA-receptor inhibitor 2-(Phosphonomethyl)pentane-1,5-dioic acid (PMPA) were performed for both tracers in two animals each. Results Autoradiography demonstrated a strong 68 Ga-PSMA and 18 F-DCFPyL binding in the peritumoral area and moderate binding in the center of the tumors. PMPA administration led to complete inhibition of 68 Ga-PSMA and 18 F-DCFPyL binding in the peritumoral region. Restoration of BBB by Dex treatment reduced EBD extravasation but 68 Ga-PSMA binding remained unchanged. Expression of activated microglia (CD11b) was low in the intra- and peritumoral area but GFAP staining revealed strong activation of astrocytes in congruency to the tracer binding in the peritumoral area. All tumors were visualized in micro PET, showing a lower tumor/brain contrast with 68 Ga-PSMA than with 18 F-DCFPyL. Conclusions High uptake of 68 Ga-PSMA and 18 F-DCFPyL in the peritumoral area of all glioma models is presumably caused by activated astrocytes. This may represent a limitation for the clinical application of PSMA ligands in gliomas.


2001 ◽  
Vol 90 (1) ◽  
pp. 261-268 ◽  
Author(s):  
Leonardo C. Clavijo ◽  
Mary B. Carter ◽  
Paul J. Matheson ◽  
Mark A. Wilson ◽  
William B. Wead ◽  
...  

In vivo pulmonary arterial catheterization was used to determine the mechanism by which platelet-activating factor (PAF) produces pulmonary edema in rats. PAF induces pulmonary edema by increasing pulmonary microvascular permeability (PMP) without changing the pulmonary pressure gradient. Rats were cannulated for measurement of pulmonary arterial pressure (Ppa) and mean arterial pressure. PMP was determined by using either in vivo fluorescent videomicroscopy or the ex vivo Evans blue dye technique. WEB 2086 was administered intravenously (IV) to antagonize specific PAF effects. Three experiments were performed: 1) IV PAF, 2) topical PAF, and 3) Escherichia coli bacteremia. IV PAF induced systemic hypotension with a decrease in Ppa. PMP increased after IV PAF in a dose-related manner. Topical PAF increased PMP but decreased Ppa only at high doses. Both PMP (88 ± 5%) and Ppa (50 ± 3%) increased during E. coli bacteremia. PAF-receptor blockade prevents changes in Ppa and PMP after both topical PAF and E. coli bacteremia. PAF, which has been shown to mediate pulmonary edema in prior studies, appears to act in the lung by primarily increasing microvascular permeability. The presence of PAF might be prerequisite for pulmonary vascular constriction during gram-negative bacteremia.


β-Lactam antibiotics resistant to β-lactamase degradation can be produced by many chemical modifications, but often at the expense of antibacterial activity. Substitution onto several positions in the molecule produces different and often selective resistance; for instance, heavily sterically hindered acyl groups give staphylococcal P-lactamase resistance to penicillins, and resistance to some enzymes from Gram-negative pathogens to both penicillins and cephalosporins. 6-α- or 7-α-substituents respectively confer a broad spectrum of resistance (e.g. cefoxitin), but changes at positions 2 or 3 have only a minor influence on enzyme susceptibility. Changes in the ring condensed with the β-lactam, such as changing ceph-3-em to ceph-2-em may greatly enhance stability. Small improvements can occur when the nuclear sulphur atom is oxidized, but a much better effect is obtained when it is replaced by another atom such as oxygen, as in clavulanic acid. This compound appears to have broad spectrum resistance which is actually due to susceptibility and subsequent product inhibition.


2011 ◽  
Vol 239-242 ◽  
pp. 1359-1363
Author(s):  
Chao Hui Zhang ◽  
Si Si Liu ◽  
Yue Tao Sun ◽  
Jun Ming Liu

Aqueous solutions have found broad usages as lubricants, in conjunction with other possible utilizations, such as in metal working and other industries. Due to the inferior lubricity, functional additives are needed to improve their tribological performances among which aqueous surfactants are exclusively included. The film forming property of aqueous solution with polyethoxylated ether added (PEOE) is measured, taking consideration of the influences of the temperature and the concentration. The addition of PEOEs into aqueous solutions will largely increase the film forming capacity. But the concentration has only a minor influence on the lubrication property of the aqueous solutions with PEOEs. The cloud point will strongly alter the film forming characteristics.


Foods ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 247
Author(s):  
Valeriu V. Cotea ◽  
Mihai Cristian Focea ◽  
Camelia Elena Luchian ◽  
Lucia Cintia Colibaba ◽  
Elena Cristina Scutarașu ◽  
...  

The occurrence of aroma constituents in sparkling wines, with direct impact on their organoleptic characteristics, is affected by several factors, for example the base-wine particularities, grapes cultivar conditions, inoculated yeasts, the aging stage, and wine-making practices. This study evaluated the influence of different four commercial yeasts (IOC FIZZ™, IOC DIVINE™, LEVULIA CRISTAL™, and IOC 18-2007™) on the volatile composition of experimental sparkling wines. For this, five sparkling wines variants from the Muscat Ottonel grape variety were obtained. The base-wine was obtained through reverse osmosis and had a predetermined alcoholic concentration (10.5% vol.). In order to fulfill the proposed purpose, the experimental sparkling wines were characterized by the physical–chemical parameters (according to International Organization of Vine and Wine methods of analysis), volatile fraction (using gas-chromatography coupled with mass spectrometry technique), and sensory descriptors. Data showed a key impact on the concentration of the volatile constituents (p < 0.05), depending on the type of inoculated yeast for the second fermentation. Regarding the sensory analysis, important differences can be observed due to the type of inoculated yeast. Only a minor influence on the physical–chemical parameters was registered.


2018 ◽  
Author(s):  
Dimitrios - Georgios Kontopoulos ◽  
Erik van Sebille ◽  
Michael Lange ◽  
Gabriel Yvon-Durocher ◽  
Timothy G. Barraclough ◽  
...  

AbstractTo better predict how populations and communities respond to climatic temperature variation, it is necessary to understand how the shape of the response of fitness-related traits to temperature evolves (the thermal performance curve). Currently, there is disagreement about the extent to which the evolution of thermal performance curves is constrained. One school of thought has argued for the prevalence of thermodynamic constraints through enzyme kinetics, whereas another argues that adaptation can—at least partly—overcome such constraints. To shed further light on this debate, we perform a phylogenetic meta-analysis of the thermal performance curves of growth rate of phytoplankton—a globally important functional group—, controlling for environmental effects (habitat type and thermal regime). We find that thermodynamic constraints have a minor influence on the shape of the curve. In particular, we detect a very weak increase of maximum performance with the temperature at which the curve peaks, suggesting a weak “hotter-is-better” constraint. Also, instead of a constant thermal sensitivity of growth across species, as might be expected from strong constraints, we find that all aspects of the thermal performance curve evolve along the phylogeny. Our results suggest that phytoplankton thermal performance curves adapt to thermal environments largely in the absence of hard thermodynamic constraints.


Biologia ◽  
2014 ◽  
Vol 69 (3) ◽  
Author(s):  
Mirela Perić ◽  
Tvrtko Dražina ◽  
Maria Špoljar ◽  
Ines Radanović ◽  
Biserka Primc ◽  
...  

AbstractAiming to establish the most frequent invertebrate taxa in drift at the small spatial scale within a moss-rich karst tufa-precipitating hydrosystem, we sampled drift among microhabitats differing in substratum type and flow conditions along a tufa barrier-cascading lotic reach. Additionally, we addressed the question of the contribution and the potential significance of meiofauna within the overall invertebrate drift at the small spatial scale. During the study period, a total of 60 invertebrate taxa were recorded in the drift. Six of these taxa belonged to the annelid/arthropod meiofauna and they represented 35% of total drift density. Macroinvertebrates found in drift were represented mainly by larval insects. The composition of the most abundant taxa in total drift was as follows: Alona spp. (Cladocera 26.7%), Riolus spp. (Coleoptera: Elmidae 13.2%), Simulium spp. (Diptera: Simuliidae 12.2%), Enchytraeidae (Oligochaeta 10.4%), Hydrachnidia (6.3%), Orthocladinae (Diptera: Chironomidae 3.9%) and Naididae (Oligochaeta 3.6%). Faunal drift densities and amounts of transported particulate matter (PM) were highest at the fast-flowing sites located at the barriers and lowest at the slow-flowing sites within pools. Similarly to the seasonal amounts of transported PM, faunal drift was lowest in winter, and peaked in autumn and in late spring/early summer. Correlation between flow velocity and PM-faunal drift densities suggested a significant effect of the dislodged PM, though a minor influence of discharge and flow velocity on faunal drift. We suggest that the small-scale habitat heterogeneity and the respective feeding and refugial strategies of the fauna, as well as faunal passive dislodgement initiated by the shear forces of the flow were the most important drivers of observed drift patterns.


1981 ◽  
Vol 240 (4) ◽  
pp. H645-H649 ◽  
Author(s):  
D. L. Fry ◽  
R. W. Mahley ◽  
S. Y. Oh

The influence of arterial wall circumferential stretch (lambda) on the 32-min diffusive mural uptake of 125I-albumin and of Evan's blue dye (EBD) across the injured endothelial surface was studied in the intimal-medial preparation of the canine descending thoracic aorta (DTA). Albumin uptake (MA nmol/cm2) was measured by standard gamma counting techniques and the corresponding EBD uptake (ME) by the reflectance method. MA and ME were measured at a physiological stretch (lambda = 1.4) and at a hypertensive stretch (lambda = 1.8) at four equispaced locations (z) along the DTA. When lambda was changed from 1.4 to 1.8, the average percentage change of MA was -2% and of ME was -4%. These decreases were not significant (P greater than 0.10), and we conclude that arterial wall stretch exerts only minor influence on the parameters governing albumin and EBD-albumin accumulation in the intimal surface of the deendothelialized arterial intimal-medial tissue system.


Sign in / Sign up

Export Citation Format

Share Document