Estrategias bioanalíticas en estudios metalómicos de fármacos de platino

En este artículo se muestra el potencial que presentan las modernas estrategias bioanalíticas en estudios metalómicos de fármacos de platino. La combinación de técnicas de separación multidimensionales cromatográficas y/o electroforéticas con la espectrometría de masas atómica ICP-MS y molecular ESI-MS/MS se presenta como una valiosa alternativa en este tipo de estudios

Development and validation of an open source quantification tool for DSC-MRI studies

Motivation. This work presents the development of an open source tool for the quantification of dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion studies. The development of this tool is motivated by the lack of open source tools implemented on open platforms to allow external developers to implement their own quantification methods easily and without the need of paying for a development license.Materials and methods. This quantification tool was developed as a plugin for the ImageJ image analysis platform using the Java programming language. A modular approach was used in the implementation of the components, in such a way that the addition of new methods can be done without breaking any of the existing functionalities. For the validation process, images from seven patients with brain tumors were acquired and quantified with the presented tool and with a widely used clinical software package. The resulting perfusion parameters were then compared.Results. Perfusion parameters and the corresponding parametric images were obtained. When no gamma-fitting is used, an excellent agreement with the tool used as a gold-standard was obtained (R²>0.8 and values are within 95% CI limits in Bland–Altman plots).Conclusion. An open source tool that performs quantification of perfusion studies using magnetic resonance imaging has been developed and validated using a clinical software package. It works as an ImageJ plugin and the source code has been published with an open source license.This work was partially supported by the Human Frontier Science Program (Research Grant 2013).Publicad

Study of CAPE effect on apoptosis induction in AGS human gastric cancer cell line

Background: Propolis is a natural product of bee and caffeic acid phenethyl ester (CAPE) is a pharmacologically important product of propolis. Objectives: The aim of this study was to investigate the effect of CAPE on apoptosis induction in AGS human gastric cancer cells. Materials and Methods: The cytotoxic effects of CAPE at different concentrations were investigated on AGS cells viability after 24 hours treatment by MTT assay. To measure the effect of CAPE on apoptosis induction, AGS cells were treated with CAPE for 24 hours and investigated by FITC Annexin V/PI staining using flow cytometry. Results: CAPE prevented growth and proliferation of AGS human gastric cancer cell line in a concentration-dependent manner with an IC50 of approximately 60 μM by a 24-hour treatment. Also CAPE caused increased induction of apoptosis in AGS cells from 1.37 % in control cells to 21.76 % in treated cells with 30 μM CAPE. Conclusions: CAPE prevents growth and proliferation of AGS human gastric cancer cell line through inducing programmed cell death in AGS cells. Therefore, CAPE could be helpful for developing chemotherapeutic agents or as an adjuvant for human gastric cancer treatment. © 2016, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences

Antitumoral and antiangiogenic activity of Portuguese propolis in in vitro and in vivo models

Propolis, a natural product, has important biological properties, however, studies with Portuguese propolis are scarce. Thus, we aimed to characterize the chemical composition and the antitumoural and antiangiogenic activities of a sample from Pereiro (Portugal). The chemical profile of our propolis sample (P10.EE) is similar to the poplar propolis type. P10.EE decreased cell viability of different tumour cells, being less cytotoxic against non-tumoural cells. P10.EE decreased MDA-MB-231 and DU145 cell proliferation and migration, with cell cycle changes and increased cell death. The increased glucose consumption and lactate production in MDA-MB-231 cells is explained by an increased expression of different metabolism-related proteins. P10.EE induced a decrease in HBMEC cells total biomass and proliferation and decreased vessel sprouting in the chicken chorioallantoic membrane. Additionally, P10.EE potentiates paclitaxel effect in MDA-MB-231 and DU145 cells. Concluding, P10.EE can be a good candidate for cancer drug development since it affects different characteristics that dictate tumorigenesis.This work was supported by the Life and Health Sciences Research Institute, University of Minho, Portugal, and Fundacao para a Ciencia e Tecnologia (FCT) (SFRH/BD/5199712012 to V.M.G.), through Fundo Europeu de Desenvolvimento Regional-QREN-COMPETE, projects PTDC/AAC-CLI1098308/2008 and PTDC/AAC-CLI/11809212010 and also CERNAS (project PEst-OE/AGR/UI0681/2011)

Unsupervised CT Lung Image Segmentation of a Mycobacterium Tuberculosis Infection Model

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that produces pulmonary damage. Radiological imaging is the preferred technique for the assessment of TB longitudinal course. Computer-assisted identification of biomarkers eases the work of the radiologist by providing a quantitative assessment of disease. Lung segmentation is the step before biomarker extraction. In this study, we present an automatic procedure that enables robust segmentation of damaged lungs that have lesions attached to the parenchyma and are affected by respiratory movement artifacts in a Mycobacterium Tuberculosis infection model. Its main steps are the extraction of the healthy lung tissue and the airway tree followed by elimination of the fuzzy boundaries. Its performance was compared with respect to a segmentation obtained using: (1) a semi-automatic tool and (2) an approach based on fuzzy connectedness. A consensus segmentation resulting from the majority voting of three experts' annotations was considered our ground truth. The proposed approach improves the overlap indicators (Dice similarity coefficient, 94\% +/- 4\%) and the surface similarity coefficients (Hausdorff distance, 8.64 mm +/- 7.36 mm) in the majority of the most difficult-to-segment slices. Results indicate that the refined lung segmentations generated could facilitate the extraction of meaningful quantitative data on disease burden.We thank Estibaliz Gomez de Mariscal, Paula Martin Gonzalez and Mario Gonzalez Arjona for helping with the manual lung annotation. The research leading to these results received funding from the Innovative Medicines Initiative (www.imi.europa.eu) Joint Undertaking under grant agreement no. 115337, whose resources comprise funding from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in kind contribution. This work was partially funded by projects TEC2013-48552-C2-1-R, RTC-2015-3772-1, TEC2015-73064-EXP and TEC2016-78052-R from the Spanish Ministerio de Economia, Industria y Competitividad, TOPUS S2013/MIT-3024 project from the regional government of Madrid and by the Department of Health, UK.S

A dataset of synthetic, maturation-informed magnetic resonance images of the human fetal brain.

Magnetic resonance imaging (MRI) is a powerful modality for investigating abnormal developmental patterns in utero. However, since it is not the first-line diagnostic tool in this sensitive population, data remain scarce and heterogeneous across scanners and hospitals. To address this, we present a novel dataset of synthetic images representative of real fetal brain MRI. Our dataset comprises 594 two-dimensional, low-resolution series of T <sub>2</sub> -weighted images corresponding to 78 developing human fetal brains between 20.0 and 34.8 weeks of gestational age. Data are generated using a new version of the Fetal Brain MR Acquisition Numerical phantom (FaBiAN) to account for local white matter heterogeneities throughout maturation. Both healthy and pathological anatomies are simulated with standard clinical settings. Two independent radiologists qualitatively assessed the realism of the simulated images. A quantitative analysis confirms an enhanced fidelity compared to the original version of the software, with further validation through its applicability to fetal brain tissue segmentation. The cohort is publicly available to support the continuous endeavor of developing advanced post-processing methods as well as cutting-edge artificial intelligence models

Reduction of motion effects in myocardial arterial spin labeling

Purpose To evaluate the accuracy and reproducibility of myocardial blood flow measurements obtained under different breathing strategies and motion correction techniques with arterial spin labeling. Methods A prospective cardiac arterial spin labeling study was performed in 12 volunteers at 3 Tesla. Perfusion images were acquired twice under breath-hold, synchronized-breathing, and free-breathing. Motion detection based on the temporal intensity variation of a myocardial voxel, as well as image registration based on pairwise and groupwise approaches, were applied and evaluated in synthetic and in vivo data. A region of interest was drawn over the mean perfusion-weighted image for quantification. Original breath-hold datasets, analyzed with individual regions of interest for each perfusion-weighted image, were considered as reference values. Results Perfusion measurements in the reference breath-hold datasets were in line with those reported in literature. In original datasets, prior to motion correction, myocardial blood flow quantification was significantly overestimated due to contamination of the myocardial perfusion with the high intensity signal of blood pool. These effects were minimized with motion detection or registration. Synthetic data showed that accuracy of the perfusion measurements was higher with the use of registration, in particular after the pairwise approach, which probed to be more robust to motion. Conclusion Satisfactory results were obtained for the free-breathing strategy after pairwise registration, with higher accuracy and robustness (in synthetic datasets) and higher intrasession reproducibility together with lower myocardial blood flow variability across subjects (in in vivo datasets). Breath-hold and synchronized-breathing after motion correction provided similar results, but these breathing strategies can be difficult to perform by patients

ABLE: Automated Brain Lines Extraction Based on Laplacian Surface Collapse.

The archetypical folded shape of the human cortex has been a long-standing topic for neuroscientific research. Nevertheless, the accurate neuroanatomical segmentation of sulci remains a challenge. Part of the problem is the uncertainty of where a sulcus transitions into a gyrus and vice versa. This problem can be avoided by focusing on sulcal fundi and gyral crowns, which represent the topological opposites of cortical folding. We present Automated Brain Lines Extraction (ABLE), a method based on Laplacian surface collapse to reliably segment sulcal fundi and gyral crown lines. ABLE is built to work on standard FreeSurfer outputs and eludes the delineation of anastomotic sulci while maintaining sulcal fundi lines that traverse the regions with the highest depth and curvature. First, it segments the cortex into gyral and sulcal surfaces; then, each surface is spatially filtered. A Laplacian-collapse-based algorithm is applied to obtain a thinned representation of the surfaces. This surface is then used for careful detection of the endpoints of the lines. Finally, sulcal fundi and gyral crown lines are obtained by eroding the surfaces while preserving the connectivity between the endpoints. The method is validated by comparing ABLE with three other sulcal extraction methods using the Human Connectome Project (HCP) test-retest database to assess the reproducibility of the different tools. The results confirm ABLE as a reliable method for obtaining sulcal lines with an accurate representation of the sulcal topology while ignoring anastomotic branches and the overestimation of the sulcal fundi lines. ABLE is publicly available via https://github.com/HGGM-LIM/ABLE .This work was supported by the project exAScale ProgramIng models for extreme Data procEssing (ASPIDE), that has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 801091. This work has received funding from “la Caixa” Foundation under the project code LCF/PR/HR19/52160001. Susanna Carmona funded by Instituto de Salud Carlos III, co-funded by European Social Fund “Investing in your future” (Miguel Servet Type I research contract CP16/00096). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Yasser Alemán-Gómez is supported by the Swiss National Science Foundation (185897) and the National Center of Competence in Research (NCCR) SYNAPSY - The Synaptic Bases of Mental Diseases, funded as well by the Swiss National Science Foundation (51AU40-1257).S

The role of snow in scavenging aerosol particles: A physical-chemical characterization

[EN] The below cloud scavenging of aerosols by snow has been analysed in León (NW Spain). Six snow events were registered over the course of one year of study. Ultrafine and accumulation aerosol particles were measured using a scanning mobility particle sizer spectrometer, while hydrometeors were characterized using a disdrometer. Furthermore, the chemical composition of the melted snow-water samples (soluble and insoluble fractions) was analysed. The scavenging coefficient (λ) showed a great variability among events. An effective washing of particles was observed during the first 30 min of snowfall. The mean change in the scavenging efficiency (%ΔC) of particle number concentration (PNC) and λ coefficient during this time interval were: i) nucleation mode: 36.3 % and 3.02 · 10−4 s−1; ii) Aitken mode: 30.4 % and 2.37 · 10−4 s−1 and iii) accumulation mode: 22.4 % and 1.77 · 10−4 s−1. The range of particle sizes that is less efficiently scavenged by snowfall was observed between 400 and 600 nm. When analyzing the whole snow event, an increase of PNC was observed. Two possible explanations underlie this behaviour: it could be caused by changes in air masses or by the resuspension of aerosol particles scavenged by snowflakes upon reaching the ground. A clear relationship was observed between Ca2+, SO42− and NO3− concentrations of aerosol particles before the snow event and the concentrations registered in the melted snow-water. The largest and smallest changes in aerosol number concentrations were caused by snowflakes of 3 and 6 mm in diameter, respectively. The particle size distributions (PSD) were fitted to log-normal distributions and the parameters were compared before and after snowfall.S