Publicaciones

Paper-Based Analytical Devices for Accurate Assessment of Transferrin Saturation in Diagnosed Clinical Samples from Ischemic Stroke Patients

Silvia Dortez, Nùria DeGregorio-Rocasolano, Mónica Millán, Teresa Gasull, Agustín G Crevillen, Alberto Escarpa. Anal Chem. 2023 Aug 22;95(33): 12391-12397. DOI: 10.1021/acs.analchem.3c01982. PMID: 37486019

https://pubmed.ncbi.nlm.nih.gov/37486019/

Abstract: For the first time, a paper-based analytical device (PAD) was developed for the assessment of transferrin saturation (TSAT), which is defined as the ratio between iron bound to transferrin (Tf) and the total iron-binding capacity (TIBC) of Tf. Both parameters were simultaneously measured on the same PAD using ferrozine as a chromophore and a smartphone as the color reader. To this end, Tf was first isolated from serum using anti-Tf immunomagnetic beads to ensure that only the Tf-bound iron was measured, improving the selectivity and accuracy of TSAT assessment. To demonstrate the practical utility of the device, it was validated by analyzing a certified reference material, showing excellent accuracy (Er < 4%) and good precision (RSD ≤ 6%). Finally, 18 diagnosed serum samples from ischemic stroke patients were analyzed by this approach, and the results were compared with those obtained by urea-PAGE, showing not only an excellent correlation (r = 0.93, p < 0.05) but that the PAD approach has become statistically identical to the free-interference urea-PAGE. In comparison with the slow, tedious, and non-miniaturized-PAGE, this PAD approach exhibited attractive characteristics such as low cost, disposability, and connectivity, showing great potential for future point-of-care testing, especially in developing countries and/or remote areas, where access to medical or clinical facilities is limited.

Funding: This work has been financially supported by the TRANSNANOAVANSENS program from the Community of Madrid (P2018/NMT-4349) (A.E.), by the grant PID2020 118154GB-I00 funded by MCIN/AEI/ 10.13039/ 501100011033 (A.E.), by the RICORS RD21/0006/0024 and 2021SGR00925 (T.G.), and by the Spanish Ministry of Economy and Competitiveness (CTQ2017-86441-C2-1-R, FPI fellowship (S. D.)).

 

Perfusion-weighted software written in Python for DSC-MRI analysis

Fernández-Rodicio S, Ferro-Costas G, Sampedro-Viana A et al. Front Neuroinform. 2023 Aug 1;17:1202156. doi: 10.3389/fninf.2023.1202156. eCollection 2023. PMID: 37593674 Free

https://pubmed.ncbi.nlm.nih.gov/37593674/

Abstract:

Introduction: Dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion studies in magnetic resonance imaging (MRI) provide valuable data for studying vascular cerebral pathophysiology in dierent rodent models of brain diseases (stroke, tumor grading, and neurodegenerative models). The extraction of these hemodynamic parameters via DSC-MRI is based on tracer kinetic modeling, which can be solved using deconvolution-based methods, among others. Most of the post-processing software used in preclinical studies is home-built and custom-designed. Its use being, in most cases, limited to the institution responsible for the development. In this study, we designed a tool that performs the hemodynamic quantification process quickly and in a reliable way for research purposes.
Methods: The DSC-MRI quantification tool, developed as a Python project, performs the basic mathematical steps to generate the parametric maps: cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), signal recovery (SR), and percentage signal recovery (PSR). For the validation process, a data set composed of MRI rat brain scans was evaluated: i) healthy animals, ii) temporal blood–brain barrier (BBB) dysfunction, iii) cerebral chronic hypoperfusion (CCH), iv) ischemic stroke, and v) glioblastoma multiforme (GBM) models. The resulting perfusion parameters were then compared with data retrieved from the literature.
Results: A total of 30 animals were evaluated with our DSC-MRI quantification tool. In all the models, the hemodynamic parameters reported from the literature are reproduced and they are in the same range as our results. The Bland– Altman plot used to describe the agreement between our perfusion quantitative analyses and literature data regarding healthy rats, stroke, and GBM models, determined that the agreement for CBV and MTT is higher than for CBF.

Conclusion: An open-source, Python-based DSC post-processing software package that performs key quantitative perfusion parameters has been developed. Regarding the dierent animal models used, the results obtained are consistent and in good agreement with the physiological patterns and values reported in the literature. Our development has been built in a modular framework to allow code customization or the addition of alternative algorithms not yet implemented

Funding: This research was funded by the Spanish Ministry of Science and Innovation (SAF2017-84267-R), PDC2021-121455-I00, Xunta de Galicia (Axencia Galega de Innovación: IN607A2022- 03), Instituto de Salud Carlos III (ISCIII) (PI17/01103, ISCIII/PI21/01256/Co-financed by the European Union), Spanish Research Network on Cerebrovascular Diseases RETICSINVICTUS PLUS (RD16/0019/0001), and RICORS-ICTUS (Cerebrovascular diseases) D21/0006/0003. MB-B is a PFIS Researcher (FI22/00200) of Instituto de Salud Carlos III. MP-M is a Sara Borrell Researcher (CD19/00033) of Instituto de Salud Carlos III. RI-R (CP22/00061) from the Miguel Servet Program of Instituto de Salud Carlos III and Co-financed by the EU. Sponsors did not participate in the study design, collection, analysis, or interpretation of the data, or in writing the report

Myeloid cells in vascular dementia and Alzheimer’s disease: Possible therapeutic targets?

García-Culebras A, Cuartero MI, Peña-Martínez C et al. Br J Pharmacol. 2024 Mar;181(6):777-798. doi: 10.1111/bph.16159. Epub 2023 Jul 7. PMID: 37282844

https://pubmed.ncbi.nlm.nih.gov/37282844/

Abstract: Growing evidence supports the suggestion that the peripheral immune system playsa role in different pathologies associated with cognitive impairment, such as vasculardementia (VD) or Alzheimer’s disease (AD). The aim of this review is to summarize,within the peripheral immune system, the implications of different types of myeloidcells in AD and VD, with a special focus on post-stroke cognitive impairment anddementia (PSCID). We will review the contributions of the myeloid lineage, fromperipheral cells (neutrophils, platelets, monocytes and monocyte-derived macro-phages) to central nervous system (CNS)-associated cells (perivascular macrophagesand microglia). Finally, we will evaluate different potential strategies for pharmacolog-ical modulation of pathological processes mediated by myeloid cell subsets, with anemphasis on neutrophils, their interaction with platelets and the process of immuno-thrombosis that triggers neutrophil-dependent capillary stall and hypoperfusion, as possible effector mechanisms that may pave the way to novel therapeutic avenues tostop dementia, the epidemic of our time.

Funding: This work was supported by grants from Spanish Ministry of Scienceand Innovation (MCIN) PID2019-106581RB-I00 (MAM), from LeducqFoundation for Cardiovascular Research TNE19CVD01 (MAM, AGCand MIC) and TNE-21CVD04 (IL and MAM), from Instituto de SaludCarlos III (ISCIII) and co-financed by the European Development Regional Fund “A Way to Achieve Europe”PI20/00535 and RICORS-ICTUSRD21/0006/0001 (IL). CNIC is supported by ISCIII. The CNIC isa Severo Ochoa Center of Excellence (CEX2020-001041-S

The role of gut microbiota in cerebrovascular disease and related dementia

Cuartero MI, García-Culebras A, Nieto-Vaquero C et al.  Br J Pharmacol. 2024 Mar;181(6):816-839. doi: 10.1111/bph.16167. Epub 2023 Jul 12.. PMID: 37328270

https://pubmed.ncbi.nlm.nih.gov/37328270/

Abstract: In recent years, increasing evidence suggests that commensal microbiota may play animportant role not only in health but also in disease including cerebrovascular dis-ease. Gut microbes impact physiology, at least in part, by metabolizing dietary factorsand host-derived substrates and then generating active compounds including toxins.The purpose of this current review is to highlight the complex interplay betweenmicrobiota, their metabolites. and essential functions for human health, ranging fromregulation of the metabolism and the immune system to modulation of brain devel-opment and function. We discuss the role of gut dysbiosis in cerebrovascular disease,specifically in acute and chronic stroke phases, and the possible implication of intesti-nal microbiota in post-stroke cognitive impairment and dementia, and we identifypotential therapeutic opportunities of targeting microbiota in this context.

Funding: This work was supported by grants from the Spanish Ministry ofScience and Innovation (Ministerio de Ciencia e Innovacion [MCIN])(PID2019-106581RB-I00 [MAM] and PID2020-117765RB-I00 [JP]),from Leducq Foundation for Cardiovascular Research (TNE19CVD01[MAM and MIC] and TNE-21CVD04 [MAM and IL]) and from Insti-tuto de Salud Carlos III (ISCIII) and co-financed by the EuropeanDevelopment Regional Fund‘A Way to Achieve Europe’(PI20/00535) and RICORS-ICTUS (RD21/0006/0001 [IL]). CNIC issupported by ISCIII, MCIN and ProCNIC Foundation and is a SeveroOchoa Center of Excellence (CEX2020-001041-S)