Control de la velocidad de degradación de materiales compuestos para aplicacions biomédicas

En este trabajo se ha utilizado la técnica del dipping, para practicar varios tipos de recubrimientos de ácido poliláctico sobre un nuevo material compuesto totalmente biodegradable formado por PLA + vidrio de fosfato; siendo ambos materiales biodegradables, y por tanto, también el compuesto. El principio de funcionamiento que presenta este tipo de técnica es actuando como barrera física entre los fluidos biológicos y el material compuesto, protegiéndolo frente a la degradación y prolongando en el tiempo las propiedades mecánicas. El control de la velocidad de degradación se ha llevado a cabo variando el grosor y el número de capas. Mediante diversas técnicas de análisis, como los ensayos a flexión o la microscopía electrónica, se han determinado las propiedades mecánicas durante las 4 semanas que ha durado el análisis, así como los cambios morfológicos del compuesto y de la capa o capas protectoras. Los resultados mostraron cambios significativos en la morfología de los materiales después de 4 semanas de inmersión en fluido fisiológico simulado (SBF). El recubrimiento de menor espesor obtuvo los mejores resultados

Control de la velocidad de degradación de materiales compuestos para aplicaciones biomédicas.

En este trabajo se ha utilizado la técnica del dipping, para practicar varios tipos de recubrimientos de ácido poliláctico sobre un nuevo material compuesto totalmente biodegradable formado por PLA + vidrio de fosfato; siendo ambos materiales biodegradables, y por tanto, también el compuesto. El principio de funcionamiento que presenta este tipo de técnica es actuando como barrera física entre los fluidos biológicos y el material compuesto, protegiéndolo frente a la degradación y prolongando en el tiempo las propiedades mecánicas. El control de la velocidad de degradación se ha llevado a cabo variando el grosor y el número de capas. Mediante diversas técnicas de análisis, como los ensayos a flexión o la microscopía electrónica, se han determinado las propiedades mecánicas durante las 4 semanas que ha durado el análisis, así como los cambios morfológicos del compuesto y de la capa o capas protectoras. Los resultados mostraron cambios significativos en la morfología de los materiales después de 4 semanas de inmersión en fluido fisiológico simulado (SBF). El recubrimiento de menor espesor obtuvo los mejores resultados

Lung fibrotic tenascin-C upregulation is associated with other extracellular matrix proteins and induced by TGFβ1

Background Idiopathic pulmonary fibrosis (IPF) is a progressive parenchymal lung disease of unknown aetiology and poor prognosis, characterized by altered tissue repair and fibrosis. The extracellular matrix (ECM) is a critical component in regulating cellular homeostasis and appropriate wound healing. The aim of our study was to determine the expression profile of highlighted ECM proteins in IPF lungs. Methods ECM gene and protein expression was analyzed by cDNA microarrays, rt-PCR, immunohistochemistry and western-blot in lungs from idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP), categorized as chronic (cHP) and subacute (saHP), and healthy lung tissue. Primary fibroblast cultures from normal subjects and fibrotic patients were studied to evaluate tenascin-C (TNC) synthesis. Results A total of 20 ECM proteins were upregulated and 6 proteins downregulated in IPF. TNC was almost undetected in normal lungs and significantly upregulated in fibrotic lungs (IPF and cHP) compared to saHP. Furthermore, it was located specifically in the fibroblastic foci areas of the fibrotic lung with a subepithelial gradient pattern. TNC levels were correlated with fibroblastic foci content in cHP lungs. Versican and fibronectin glycoproteins were associated with TNC, mainly in fibroblastic foci of fibrotic lungs. Fibroblasts from IPF patients constitutively synthesized higher levels of TNC than normal fibroblasts. TNC and α-sma was induced by TGF-β1 in both fibrotic and normal fibroblasts. TNC treatment of normal and fibrotic fibroblasts induced a non-significant increased α-sma mRNA. Conclusions The difference in ECM glycoprotein content in interstitial lung diseases could contribute to the development of lung fibrosis. The increase of TNC in interstitial areas of fibrotic activity could play a key role in the altered wound healing

Random Forest-Based Prediction of Stroke Outcome

[Abstract] We research into the clinical, biochemical and neuroimaging factors associated with the outcome of stroke patients to generate a predictive model using machine learning techniques for prediction of mortality and morbidity 3-months after admission. The dataset consisted of patients with ischemic stroke (IS) and non-traumatic intracerebral hemorrhage (ICH) admitted to Stroke Unit of a European Tertiary Hospital prospectively registered. We identified the main variables for machine learning Random Forest (RF), generating a predictive model that can estimate patient mortality/morbidity according to the following groups: (1) IS + ICH, (2) IS, and (3) ICH. A total of 6022 patients were included: 4922 (mean age 71.9 ± 13.8 years) with IS and 1100 (mean age 73.3 ± 13.1 years) with ICH. NIHSS at 24, 48 h and axillary temperature at admission were the most important variables to consider for evolution of patients at 3-months. IS + ICH group was the most stable for mortality prediction [0.904 ± 0.025 of area under the receiver operating characteristics curve (AUC)]. IS group presented similar results, although variability between experiments was slightly higher (0.909 ± 0.032 of AUC). ICH group was the one in which RF had more problems to make adequate predictions (0.9837 vs. 0.7104 of AUC). There were no major differences between IS and IS + ICH groups according to morbidity prediction (0.738 and 0.755 of AUC) but, after checking normality with a Shapiro Wilk test with the null hypothesis that the data follow a normal distribution, it was rejected with W = 0.93546 (p-value < 2.2e−16). Conditions required for a parametric test do not hold, and we performed a paired Wilcoxon Test assuming the null hypothesis that all the groups have the same performance. The null hypothesis was rejected with a value < 2.2e−16, so there are statistical differences between IS and ICH groups. In conclusion, machine learning algorithms RF can be effectively used in stroke patients for long-term outcome prediction of mortality and morbidity.This study was partially supported by grants from the Spanish Ministry of Science and Innovation (SAF2017-84267-R), Xunta de Galicia (Axencia Galega de Innovación (GAIN): IN607A2018/3), Instituto de Salud Carlos III (ISCIII) (PI17/00540, PI17/01103), Spanish Research Network on Cerebrovascular Diseases RETICS-INVICTUS PLUS (RD16/0019) and by the European Union FEDER program. T. Sobrino (CPII17/00027), F. Campos (CPII19/00020) are recipients of research contracts from the Miguel Servet Program (Instituto de Salud Carlos III). General Directorate of Culture, Education and University Management of Xunta de Galicia (ED431G/01,252 ED431D 2017/16), “Galician Network for Colorectal Cancer Research" (Ref. ED431D 2017/23), Competitive Reference Groups (ED431C 2018/49), Spanish Ministry of Economy and Competitiveness via funding of the unique installation BIOCAI (UNLC08-1E-002, UNLC13-13–3503), European Regional Development Funds (FEDER).Xunta de Galicia; IN607A2018/3Xunta de Galicia; ED431G/01,252Xunta de Galicia; ED431D 2017/1

Fibroblast viability and phenotypic changes within glycated stiffened three-dimensional collagen matrices

Background: There is growing interest in the development of cell culture assays that enable the rigidity of the extracellular matrix to be increased. A promising approach is based on three-dimensional collagen type I matrices that are stiffened by cross-linking through non-enzymatic glycation with reducing sugars. Methods: The present study evaluated the biomechanical changes in the non-enzymatically glycated type I collagen matrices, including collagen organization, the advanced glycation end products formation and stiffness achievement. Gels were glycated with ribose at different concentrations (0, 5, 15, 30 and 240 mM). The viability and the phenotypic changes of primary human lung fibroblasts cultured within the non-enzymatically glycated gels were also evaluated along three consecutive weeks. Statistical tests used for data analyze were MannWhitney U, Kruskal Wallis, Student's t-test, two-way ANOVA, multivariate ANOVA, linear regression test and mixed linear model. Results: Our findings indicated that the process of collagen glycation increases the stiffness of the matrices and generates advanced glycation end products in a ribose concentration-dependent manner. Furthermore, we identified optimal ribose concentrations and media conditions for cell viability and growth within the glycated matrices. The microenvironment of this collagen based three-dimensional culture induces α-smooth muscle actin and tenascin-C fibroblast protein expression. Finally, a progressive contractile phenotype cell differentiation was associated with the contraction of these gels. Conclusions: The use of non-enzymatic glycation with a low ribose concentration may provide a suitable model with a mechanic and oxidative modified environment with cell s embedded in it, which allowed cell proliferation and induced fibroblast phenotypic changes. Such culture model could be appropriate for investigations of the behavior and phenotypic changes in cells that occur during lung fibrosis as well as for testing different antifibrotic therapies in vitro

Intra- and extra-hospital improvement in ischemic stroke patients: influence of reperfusion therapy and molecular mechanisms

Neuroprotective treatments in ischemic stroke are focused to reduce the pernicious effect of excitotoxicity, oxidative stress and inflammation. However, those cellular and molecular mechanisms may also have beneficial effects, especially during the late stages of the ischemic stroke. The objective of this study was to investigate the relationship between the clinical improvement of ischemic stroke patients and the time-dependent excitotoxicity and inflammation. We included 4295 ischemic stroke patients in a retrospective study. The main outcomes were intra and extra-hospital improvement. High glutamate and IL-6 levels at 24 hours were associated with a worse intra-hospital improvement (OR:0.993, 95%CI: 0.990-0.996 and OR:0.990, 95%CI: 0.985-0.995). High glutamate and IL-6 levels at 24 hours were associated with better extra-hospital improvement (OR:1.13 95%CI, 1.07-1.12 and OR:1.14, 95%CI, 1.09-1.18). Effective reperfusion after recanalization showed the best clinical outcome. However, the long term recovery is less marked in patients with an effective reperfusion. The variations of glutamate and IL6 levels in the first 24 hours clearly showed a relationship between the molecular components of the ischemic cascade and the clinical outcome of patients. Our findings suggest that the rapid reperfusion after recanalization treatment blocks the molecular response to ischemia that is associated with restorative processes

Litter size components in a full diallel cross of four maternal lines of rabbits

[EN] A crossbreeding experiment between 4 Spanish maternal lines of rabbits was performed to estimate crossbreeding effects on litter size components. The experiment was designed as a complete diallel cross involving 4 lines selected for litter size at weaning (A, V, H, and LP [L]) and their 12 simple crosses. Does from these 16 genetic groups were distributed among 4 Spanish farms, but only V line was present in all farms, allowing connectivity of the data. A total of 2,015 does in the third, fourth, or fifth gestations were subjected to laparoscopy. The recorded traits were ovulation rate (OR), number of implanted embryos (IE), total born (TB), embryo survival (ES), foetal survival (FS), and prenatal survival (PS). The differences in direct genetic effects, maternal genetic effects, and individual heterosis between the lines were estimated according to Dickerson s model. Line A was significantly inferior to lines V and H, whereas line LP was similar to A line, but for FS and PS, line A showed the best values, followed by line LP. Comparing crossbred groups to line V, significant differences were shown favoring crossbred groups for OR and IE. The crossbred groups presented high implantation rate, but the foetal survival was lower than in V line. Important values for commercial production were presented by some crosses for OR (HV, 1.26 ova), IE (AH, 1.50 embryos; HV, 1.41 embryos), and TB (AH, 0.82 rabbits; HV, 0.78 rabbits). Relevant and significant reciprocal effects were found, especially for OR in all cases except the LV and VL crosses. These differences become nonsignificant in most of the other traits. Regarding direct genetic effects, line A presented lower estimates than the other lines with important values for OR, but the opposite was observed for FS. The maternal effects were significant only for some contrasts in OR and revealed that the LP line was inferior to the others (1.08 ova compared to the A line, 1.23 compared to the H line, and 0.38 compared to the V line). In general, high positive values for heterosis were found in crossbred does for OR and IE. The crosses, where lines A and H were involved, showed significant heterosis. The highest values were obtained by crossing lines A and H (1.18 ova for OR, 1.87 embryos for IE) followed by the cross between lines H and V. Crosses between line LP and the other lines had a negative heterosis for FS and PS.This work was supported by the Spanish project AGL2011-30170 from the Spanish National Research Plan.Mohamed Ragab, M.; Sánchez Serrano, JP.; Mínguez Balaguer, C.; Vicente Antón, JS.; Baselga Izquierdo, M. (2014). Litter size components in a full diallel cross of four maternal lines of rabbits. Journal of Animal Science. 92(8):3231-3236. https://doi.org/10.2527/jas.2013-7286S3231323692