1,721,033 research outputs found
Pharmacokinetic modelling of N-(4-[(18)F]fluorobenzoyl)interleukin-2 binding to activated lymphocytes in an xenograft model of inflammation.
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
11C-Hydroxytryptophan Uptake and Metabolism in Endocrine and Exocrine Pancreas
No full textDetermination of the residual β-cell mass using noninvasive tools might help to follow up the efficacy of new treatments in both type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus, including islet transplantation. β-cells are neuroendocrine cells that can take up and metabolize the serotonin precursor 5-hydroxytryptophan. The serotonin pathway may therefore be an attractive target for the development of an imaging tracer for residual β-cell mass. The aim of this study was to evaluate the uptake mechanism and the retention of the PET tracer (11)C-hydroxytryptophan in endocrine and exocrine pancreas in vitro and in vivo.
METHODS:
The exocrine human pancreas carcinoma cell line (PANC-1) and the endocrine human insulinoma cell line (CM) were applied for in vitro (11)C-hydroxytryptophan accumulation/efflux experiments and blocking studies using inhibitors of key enzymes and transporters involved in the serotonin pathway. Animal experiments were performed on normal Wistar rats and on rats pretreated with the monoamine oxidase (MAO) inhibitor clorgyline. After intravenous injection of (11)C-hydroxytryptophan, a 60-min dynamic PET scan was acquired followed by an ex vivo biodistribution study. Autoradiography and hematoxylin-eosin staining were performed on the dissected pancreas to localize the radioactivity within the pancreatic tissue.
RESULTS:
(11)C-hydroxytryptophan accumulated rapidly in both endocrine CM cells and exocrine PANC-1 cells. In the exocrine cells, a rapid efflux of radioactivity was observed, whereas most radioactivity remained trapped in the endocrine cells. PET images showed clear accumulation of (11)C-hydroxytryptophan in the pancreas in both animal groups, but with a significant 3-fold higher retention of the radiopharmaceutical in clorgyline-treated animals. Ex vivo biodistribution studies confirmed the results obtained by PET. Autoradiographs did not discriminate between the exocrine and endocrine pancreas in control animals, whereas autoradiographs showed intense radioactive spots colocalized with the islets of Langerhans in clorgyline-treated animals.
CONCLUSION:
(11)C-hydroxytryptophan is trapped in β-cells but not in exocrine pancreatic cells. β-cell selectivity can be strongly enhanced by inhibition of MAO-A. This observation offers perspectives for the development of a more selective PET tracer for β-cell mass, based on an (11)C-hydroxytryptophan derivative with increased resistance toward degradation by MAO-A
Development and testing of a new disposable sterile device for labelling white blood cells.
Full text linkAim. White blood cell (WBC) labelling requires isolation of cells from patient's blood under sterile conditions using sterile materials, buffers and disposables under good manufacturing practice (GMP) conditions. Till now, this limited the use of white blood cell scintigraphy (WBC-S) only to well equipped laboratories with trained personnel. We invented, developed and tested a disposable, sterile, closed device for blood manipulation, WBC purification and radionuclide labelling without exposing patient's blood and the operator to contamination risks. This device prototype and a final industrialized device (Leukokit®) were tested for WBC labelling and compared to standard procedure. Leukokit® was also tested in an international multi-centre study for easiness of WBC purification and labelling. Methods. On the device prototype we tested in parallel, with blood samples from 7 volunteers, the labelling procedure compared to the standard procedure of the International Society of Radiolabeled Blood Elements (ISORBE) consensus protocol with respect to cell recovery, labelling efficiency (LE), cell viability (Trypan Blue test) and sterility (haemoculture). On the final Leukokit® we tested the biocompatibility of all components, and again the LE, erythro-sedimentation rate, cell viability, sterility and apyrogenicity. ACD-A, HES and PBS provided by Leukokit® were also compared to Heparin, Dextran and autologous plasma, respectively. In 4 samples, we tested the chemotactic activity of purified WBC against 1 mg/ml of lipopolysaccharide (LPS) and Chemotaxis of 99mTc-HMPAO-labelled WBC (925 MBq) was compared to that of unlabelled cells. For the multi-centre study, 70 labellings were performed with the Leukokit® by 9 expert operators and 3 beginners from five centers using blood from both patients and volunteers. Finally, Media-Fill tests were performed by 3 operators on two different days (11 procedures) by replacing blood and kit reagents with bacterial culture media (Tryptic Soy Broth) and testing sterility of aliquots of the medium at the end of procedure. Results. Tests performed with the prototype showed no significant differences with the standard procedure but a faster and safer approach. Tests performed with the final Leukokit® confirmed full biocompatibility, sterility and apyrogenicity of all reagents and plastic ware. Average WBC recovery with Leukokit® was comparable to that of the ISORBE protocol (117×10 6±24×106 vs. 132×106± 29×106 cells, P=not significant). No differences in red blood cells and platelet content were observed. LE was 82% ± 3% for Leukokit® and 65±5% for control (P=0.0003) being PBS vs autologous plasma the main reason of such difference. Cell viability was always >99.9% in both conditions. Chemotactic tests showed no differences between all Leukokit® samples and controls. Haemocultures and Media-Fill tests were always sterile. The procedure was well accepted by expert operators and beginners, with a very fast learning curve (confidence after 2±2 labellings). Conclusion. The invented device offers high level of protection to operators and patients. The derived Leukokit® is safe and easy to use, and gives a high LE of WBC without affecting cell viability and function. Being a registered closed, sterile medical device, it may allow easier and faster WBC labelling that is not limited to only well equipped laboratories. Also simultaneously labelling of multiple patients is possible
Use of 99m-Technetium labelled rituximab for imaging of patients with chronic inflammatory diseases
No full textVariations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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