Insight into Glutamatergic Involvement in Rewarding Effects of Mephedrone in Rats: In Vivo and Ex Vivo Study

AbstractMephedrone is a widely used drug of abuse, exerting its effects by interacting with monoamine transporters. Although this mechanism has been widely studied heretofore, little is known about the involvement of glutamatergic transmission in mephedrone effects. In this study, we comprehensively evaluated glutamatergic involvement in rewarding effects of mephedrone using an interdisciplinary approach including (1) behavioural study on effects of memantine (non-selective NMDA antagonist) on expression of mephedrone-induced conditioned place preference (CPP) in rats; (2) evaluation of glutamate concentrations in the hippocampus of rats following 6 days of mephedrone administration, using in vivo magnetic resonance spectroscopy (MRS); and (3) determination of glutamate levels in the hippocampus of rats treated with mephedrone and subjected to MRS, using ion-exchange chromatography. In the presented research, we confirmed priorly reported mephedrone-induced rewarding effects in the CPP paradigm and showed that memantine (5 mg/kg) was able to reverse the expression of this effect. MRS study showed that subchronic mephedrone administration increased glutamate level in the hippocampus when measured in vivo 24 h (5 mg/kg, 10 mg/kg and 20 mg/kg) and 2 weeks (5 mg/kg and 20 mg/kg) after last injection. Ex vivo chromatographic analysis did not show significant changes in hippocampal glutamate concentrations; however, it showed similar results as obtained in the MRS study proving its validity. Taken together, the presented study provides new insight into glutamatergic involvement in rewarding properties of mephedrone.

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Electronic determination of root canal working length in primary molar teeth: an in vivo and ex vivo study

International Endodontic Journal ◽

10.1111/j.1365-2591.2010.01839.x ◽

2011 ◽

Vol 44 (5) ◽

pp. 402-406 ◽

Cited By ~ 17

Author(s):

A. P. C. A. Beltrame ◽

T. C. Triches ◽

N. Sartori ◽

M. Bolan

Keyword(s):

Root Canal ◽

Ex Vivo ◽

Primary Molar ◽

Working Length ◽

Molar Teeth ◽

Ex Vivo Study

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An insight into the determination of size and number concentration of silver nanoparticles in blood using single particle ICP-MS (spICP-MS): Feasibility of application to samples relevant to in vivo toxicology studies

Journal of Analytical Atomic Spectrometry ◽

10.1039/d1ja00068c ◽

2021 ◽

Author(s):

Isabel Abad-Álvaro ◽

Diego Leite ◽

Dorota Bartczak ◽

Susana Cuello ◽

Beatriz Gomez-Gomez ◽

...

Keyword(s):

Silver Nanoparticles ◽

Single Particle ◽

Number Concentration ◽

Biological Matrices ◽

Icp Ms ◽

Toxicological Studies ◽

Insight Into

Toxicological studies concerning nanomaterials in complex biological matrices usually require a carefully designed workflow that involves handling, transportation and preparation of a large number of samples without affecting the nanoparticle...

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64Cu-ATSM/64Cu-Cl2 and their relationship to hypoxia in glioblastoma: a preclinical study

EJNMMI Research ◽

10.1186/s13550-019-0586-6 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Elodie A. Pérès ◽

Jérôme Toutain ◽

Louis-Paul Paty ◽

Didier Divoux ◽

Méziane Ibazizène ◽

...

Keyword(s):

Ex Vivo ◽

In Vitro Study ◽

Tumor Location ◽

Preclinical Study ◽

Significant Rise ◽

Lower Oxygen ◽

Cu Complexes ◽

Ex Vivo Study

Abstract Background Diacetyl-bis(N4-methylthiosemicarbazone), labeled with 64Cu (64Cu-ATSM) has been suggested as a promising tracer for imaging hypoxia. However, various controversial studies highlighted potential pitfalls that may disable its use as a selective hypoxic marker. They also highlighted that the results may be tumor location dependent. Here, we first analyzed uptake of Cu-ATSM and its less lipophilic counterpart Cu-Cl2 in the tumor over time in an orthotopic glioblastoma model. An in vitro study was also conducted to investigate the hypoxia-dependent copper uptake in tumor cells. We then further performed a comprehensive ex vivo study to compare 64Cu uptake to hypoxic markers, specific cellular reactions, and also transporter expression. Methods μPET was performed 14 days (18F-FMISO), 15 days (64Cu-ATSM and 64Cu-Cl2), and 16 days (64Cu-ATSM and 64Cu-Cl2) after C6 cell inoculation. Thereafter, the brains were withdrawn for further autoradiography and immunohistochemistry. C6 cells were also grown in hypoxic workstation to analyze cellular uptake of Cu complexes in different oxygen levels. Results In vivo results showed that Cu-ASTM and Cu-Cl2 accumulated in hypoxic areas of the tumors. Cu-ATSM also stained, to a lesser extent, non-hypoxic regions, such as regions of astrogliosis, with high expression of copper transporters and in particular DMT-1 and CTR1, and also characterized by the expression of elevated astrogliosis. In vitro results show that 64Cu-ATSM showed an increase in the uptake only in severe hypoxia at 0.5 and 0.2% of oxygen while for 64Cu-Cl2, the cell retention was significantly increased at 5% and 1% of oxygen with no significant rise at lower oxygen percentages. Conclusion In the present study, we show that Cu-complexes undoubtedly accumulate in hypoxic areas of the tumors. This uptake may be the reflection of a direct dependency to a redox metabolism and also a reflection of hypoxic-induced overexpression of transporters. We also show that Cu-ATSM also stained non-hypoxic regions such as astrogliosis.

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Comparison of the Resistance to Bending Forces of the 4.5 LCP Plate-rod Construct and of 4.5 LCP Alone Applied to Segmental Femoral Defects in Miniature Pigs

Acta Veterinaria Brno ◽

10.2754/avb201079040613 ◽

2010 ◽

Vol 79 (4) ◽

pp. 613-620 ◽

Cited By ~ 2

Author(s):

Lucie Urbanová ◽

Robert Srnec ◽

Pavel Proks ◽

Ladislav Stehlík ◽

Zdeněk Florian ◽

...

Keyword(s):

Ex Vivo ◽

Femoral Diaphysis ◽

Miniature Pig ◽

Femoral Bone ◽

Bone Implant ◽

Miniature Pigs ◽

Bone Defect Healing ◽

Considerable Strain

The study deals with the determination of mechanical properties, namely resistance to bending forces, of flexible buttress osteosynthesis using two different bone-implant constructs stabilizing experimental segmental femoral bone defects (segmental ostectomy) in a miniature pig ex vivo model using 4.5 mm titanium LCP and a 3 mm intramedullary pin (“plate and rod” construct) (PR-LCP), versus the 4.5 mm titanium LCP alone (A-LCP). The “plate and rod” fixation (PR-LCP) of the segmental femoral defect is significantly more resistant (p < 0.05) to bending forces (200 N, 300 N, and 500 N) than LCP alone (A-LCP). Stabilisation of experimental segmental lesions of the femoral diaphysis in miniature pigs by flexible bridging osteosynthesis 4.5 mm LCP in combination with the “plate and rod” construct appears to be a suitable fixation of non-reducible fractures where considerable strain of the implants by bending forces can be assumed. These findings will be used in upcoming in vivo experiments in the miniature pig to investigate bone defect healing after transplantation of mesenchymal stem cells in combination with biocompatible scaffolds.

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About Puncture Testing Applied for Mechanical Characterization of Fetal Membranes

Journal of Biomechanical Engineering ◽

10.1115/1.4028446 ◽

2014 ◽

Vol 136 (11) ◽

Cited By ~ 6

Author(s):

Wilfried Bürzle ◽

Edoardo Mazza ◽

John J. Moore

Keyword(s):

Deformation Behavior ◽

Mechanical Characterization ◽

Ex Vivo ◽

Fetal Membrane ◽

Membrane Rupture ◽

Resistance To Deformation ◽

Ex Vivo Testing ◽

Insight Into

Puncture testing has been applied in several studies for the mechanical characterization of human fetal membrane (FM) tissue, and significant knowledge has been gained from these investigations. When comparing results of mechanical testing (puncture, inflation, and uniaxial tension), we have observed discrepancies in the rupture sequence of FM tissue and significant differences in the deformation behavior. This study was undertaken to clarify these discrepancies. Puncture experiments on FM samples were performed to reproduce previous findings, and numerical simulations were carried out to rationalize particular aspects of membrane failure. The results demonstrate that both rupture sequence and resistance to deformation depend on the samples' fixation. Soft fixation leads to slippage in the clamping, which reduces mechanical loading of the amnion layer and results in chorion rupturing first. Conversely, the stiffer, stronger, and less extensible amnion layer fails first if tight fixation is used. The results provide a novel insight into the interpretation of ex vivo testing as well as in vivo membrane rupture.

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Methylene Blue Staining of Dysplastic and Nondysplastic Barrett's Esophagus: An In Vivo and Ex Vivo Study

Endoscopy ◽

10.1055/s-2001-14427 ◽

2001 ◽

Vol 33 (5) ◽

pp. 391-400 ◽

Cited By ~ 103

Author(s):

M. I. Canto ◽

S. Setrakian ◽

J. E. Willis ◽

A. Chak ◽

R. E. Petras ◽

...

Keyword(s):

Methylene Blue ◽

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Ex Vivo ◽

Blue Staining ◽

Ex Vivo Study

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Structure Determination of Microtubules and Pili: Past, Present, and Future Directions

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.830304 ◽

2022 ◽

Vol 8 ◽

Author(s):

James A. Garnett ◽

Joseph Atherton

Keyword(s):

Ex Vivo ◽

Structural Heterogeneity ◽

Resonance Spectroscopy ◽

Future Directions ◽

Computational Approaches ◽

The Past ◽

Major Shift ◽

Technical Innovations

Historically proteins that form highly polymeric and filamentous assemblies have been notoriously difficult to study using high resolution structural techniques. This has been due to several factors that include structural heterogeneity, their large molecular mass, and available yields. However, over the past decade we are now seeing a major shift towards atomic resolution insight and the study of more complex heterogenous samples and in situ/ex vivo examination of multi-subunit complexes. Although supported by developments in solid state nuclear magnetic resonance spectroscopy (ssNMR) and computational approaches, this has primarily been due to advances in cryogenic electron microscopy (cryo-EM). The study of eukaryotic microtubules and bacterial pili are good examples, and in this review, we will give an overview of the technical innovations that have enabled this transition and highlight the advancements that have been made for these two systems. Looking to the future we will also describe systems that remain difficult to study and where further technical breakthroughs are required.

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