Benchmarking of three-dimensional multicomponent lattice Boltzmann equation

We present a challenging validation of phase field multi-component lattice Boltzmann equation (MCLBE) simulation against the Re = 0 Stokes flow regime Taylor-Einstein theory of dilute suspension viscosity. By applying a number of recent advances in the understanding and the elimination of the interfacial micro-current artefact, extending to 3D a class of stability-enhancing multiple relaxation time collision models (which require no explicit collision matrix, note) and developing new interfacial interpolation schemes, we are able to obtain data which show that MCLBE may be applied in new flow regimes. Our data represent one of the most stringent tests yet attempted on LBE-one which received wisdom would preclude on grounds of overwhelming artefact flow

DataSheet_1_PET/CT imaging detects intestinal inflammation in a mouse model of doxorubicin-induced mucositis.docx

IntroductionA severe side effect of cancer chemotherapy is the development of gastrointestinal mucositis, characterised by mucosal inflammation. We investigated if 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography combined with computed tomography (2-[18F]FDG-PET/CT) could visualise gastrointestinal mucositis in mice treated with the chemotherapeutic agent doxorubicin.MethodsIn this study, gastrointestinal inflammation was longitudinally evaluated by 2-[18F]FDG-PET/CT scans before and 1, 3, 6, and 10 days after treatment with doxorubicin. Doxorubicin-treated mice were compared to saline-treated littermates using the abdominal standard uptake value of 2-[18F]FDG corrected for body weight (SUVBW).ResultsAbdominal SUVBW was significantly increased on day 1 (p BW returned to baseline levels on day 10. In the doxorubicin group, the largest weight loss was observed on day 3 (control vs doxorubicin, mean percent of baseline weight: (98.5 ± 3.2% vs 87.9 ± 4.6%, p DiscussionTogether, these findings indicate that sequential 2-[18F]FDG-PET/CT scans can objectively quantify and evaluate the development and resolution of intestinal inflammation over time in a mouse model of doxorubicin-induced mucositis.</p

Video_1_PET/CT imaging detects intestinal inflammation in a mouse model of doxorubicin-induced mucositis.wmv

IntroductionA severe side effect of cancer chemotherapy is the development of gastrointestinal mucositis, characterised by mucosal inflammation. We investigated if 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography combined with computed tomography (2-[18F]FDG-PET/CT) could visualise gastrointestinal mucositis in mice treated with the chemotherapeutic agent doxorubicin.MethodsIn this study, gastrointestinal inflammation was longitudinally evaluated by 2-[18F]FDG-PET/CT scans before and 1, 3, 6, and 10 days after treatment with doxorubicin. Doxorubicin-treated mice were compared to saline-treated littermates using the abdominal standard uptake value of 2-[18F]FDG corrected for body weight (SUVBW).ResultsAbdominal SUVBW was significantly increased on day 1 (p BW returned to baseline levels on day 10. In the doxorubicin group, the largest weight loss was observed on day 3 (control vs doxorubicin, mean percent of baseline weight: (98.5 ± 3.2% vs 87.9 ± 4.6%, p DiscussionTogether, these findings indicate that sequential 2-[18F]FDG-PET/CT scans can objectively quantify and evaluate the development and resolution of intestinal inflammation over time in a mouse model of doxorubicin-induced mucositis.</p

DataSheet1_A pilot study of cerebral metabolism and serotonin 5-HT2A receptor occupancy in rats treated with the psychedelic tryptamine DMT in conjunction with the MAO inhibitor harmine.pdf

Rationale: The psychedelic effects of the traditional Amazonian botanical decoction known as ayahuasca are often attributed to agonism at brain serotonin 5-HT2A receptors by N,N-dimethyltryptamine (DMT). To reduce first pass metabolism of oral DMT, ayahuasca preparations additionally contain reversible monoamine oxidase A (MAO-A) inhibitors, namely β-carboline alkaloids such as harmine. However, there is lacking biochemical evidence to substantiate this pharmacokinetic potentiation of DMT in brain via systemic MAO-A inhibition.Objectives: We measured the pharmacokinetic profile of harmine and/or DMT in rat brain, and tested for pharmacodynamic effects on brain glucose metabolism and DMT occupancy at brain serotonin 5-HT2A receptors.Methods: We first measured brain concentrations of harmine and DMT after treatment with harmine and/or DMT at low sub-cutaneous doses (1 mg/kg each) or harmine plus DMT at moderate doses (3 mg/kg each). In the same groups of rats, we also measured ex vivo the effects of these treatments on the availability of serotonin 5-HT2A receptors in frontal cortex. Finally, we explored effects of DMT and/or harmine (1 mg/kg each) on brain glucose metabolism with [18F]FDG-PET.Results: Results confirmed that co-administration of harmine inhibited the formation of the DMT metabolite indole-3-acetic acid (3-IAA) in brain, while correspondingly increasing the cerebral availability of DMT. However, we were unable to detect any significant occupancy by DMT at 5-HT2A receptors measured ex vivo, despite brain DMT concentrations as high as 11.3 µM. We did not observe significant effects of low dose DMT and/or harmine on cerebral [18F]FDG-PET uptake.Conclusion: These preliminary results call for further experiments to establish the dose-dependent effects of harmine/DMT on serotonin receptor occupancy and cerebral metabolism.</p

Additional file 1: Figure S1. of Further validation to support clinical translation of [18F]FTC-146 for imaging sigma-1 receptors

FTC-146, SN-56 and Vesamicol binding affinity to VAChT. (DOC 171 kb

Additional file 6: Table S3. of Further validation to support clinical translation of [18F]FTC-146 for imaging sigma-1 receptors

Summary of [19F]FTC-146 toxicity study in rats. (DOC 34 kb

Additional file 2: Figure S2. of Further validation to support clinical translation of [18F]FTC-146 for imaging sigma-1 receptors

Representative MR images showing how regions of interest (ROIs) were drawn for 1 = cortex; 2 = caudate putamen; 3 = hippocampus, 4 = cerebellum during PET/MR image analysis. Whole brain ROIs were drawn using the skull from the CT image as a guide. (DOC 573 kb