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Bellmann S.,TNO | Carlander D.,Nanotechnology Industries Association | Fasano A.,Harvard University | Momcilovic D.,U.S. Food and Drug Administration | And 7 more authors.
Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology | Year: 2015

Many natural chemicals in food are in the nanometer size range, and the selective uptake of nutrients with nanoscale dimensions by the gastrointestinal (GI) tract is a normal physiological process. Novel engineered nanomaterials (NMs) can bring various benefits to food, e.g., enhancing nutrition. Assessing potential risks requires an understanding of the stability of these entities in the GI lumen, and an understanding of whether or not they can be absorbed and thus become systemically available. Data are emerging on the mammalian in vivo absorption of engineered NMs composed of chemicals with a range of properties, including metal, mineral, biochemical macromolecules, and lipid-based entities. In vitro and in silico fluid incubation data has also provided some evidence of changes in particle stability, aggregation, and surface properties following interaction with luminal factors present in the GI tract. The variables include physical forces, osmotic concentration, pH, digestive enzymes, other food, and endogenous biochemicals, and commensal microbes. Further research is required to fill remaining data gaps on the effects of these parameters on NM integrity, physicochemical properties, and GI absorption. Knowledge of the most influential luminal parameters will be essential when developing models of the GI tract to quantify the percent absorption of food-relevant engineered NMs for risk assessment. © 2015 The Authors.


PubMed | Health Research Institute Hospital La Fe, Leitat Technological Center and University of Oslo
Type: | Journal: Scientific reports | Year: 2017

The prompt and reliable identification of infants at risk of hypoxic-ischemic encephalopathy secondary to perinatal asphyxia in the first critical hours is important for clinical decision-making and yet still remains a challenge. This work strives for the evaluation of a panel of metabolic biomarkers that have been associated with the hypoxic-ischemic insult in the perinatal period. Plasma and urine samples from a consolidated newborn piglet model of hypoxia and withdrawn before and at different time points after a hypoxic insult were analyzed and compared to a control group. Time-dependent metabolic biomarker profiles were studied and observed patterns were similar to those of lactate levels, which are currently considered the gold standard for assessing hypoxia. Class prediction performance could be improved by the use of a combination of the whole panel of determined metabolites in plasma as compared to lactate values. Using a multivariate model including lactate together with the studied metabolic biomarkers allowed to improve the prediction performance of duration of hypoxia time, which correlates with the degree of brain damage. The present study evidences the usefulness of choline and related metabolites for improving the early assessment of the severity of the hypoxic insult.


PubMed | Health Research Institute Hospital La Fe, Leitat Technological Center and University of Oslo
Type: Journal Article | Journal: Pediatric research | Year: 2016

Perinatal hypoxic-ischemic brain damage is a major cause of mortality and morbidity in the neonatal period. Currently, limited ranges of biochemical tests assessing the intensity and duration of hypoxia are ready for clinical use. However, the need to initiate hypothermia therapy early after the clinical suspicion of hypoxic-ischemic encephalopathy requires the availability of early and reliable hypoxia markers. We have sought these biomarkers in an experimental model of hypoxia reoxygenation.Hypoxia and hypotension were induced in newborn piglets following a standardized model and reoxygenation was carried out using room air (RA). An untargeted liquid chromatography-time of flight mass spectrometry (LC-TOFMS) approach was used to assess changes in the metabolomic profile of plasma samples after intense hypoxia and upon reoxygenation.At the end of hypoxia, the plasma metabolome showed an increased plasma concentration of analytes reflecting a metabolic adaptation to prolonged anaerobiosis. However, after resuscitation, metabolite levels returned to the starting values.Severe hypoxia induces early, significant, and transient changes of specific metabolites in the plasma metabolome, which represent a snapshot of the biochemical adaptation of mammals to intense hypoxia. These metabolites could have applicability in predicting the severity of hypoxia in the clinical setting.


Beskers T.F.,Karlsruhe Institute of Technology | Beskers T.F.,PSS Polymer Standards Service GmbH | Brandstetter M.,Vienna University of Technology | Kuligowski J.,Health Research Institute Hospital la Fe | And 3 more authors.
Analyst | Year: 2014

This work introduces a tunable mid-infrared (mid-IR) external cavity quantum cascade laser (EC-QCL) as a new molecular specific detector in liquid chromatography. An EC-QCL with a maximum tunability of 200 cm-1 (1030-1230 cm-1) was coupled to isocratic high performance liquid chromatography (HPLC) for the separation of sugars with a cation exchange column (counter ion: Ca2+) and distilled water as the mobile phase. Transmission measurements in a 165 μm thick flow cell allowed for on-line coupling and independent quantification of glucose, fructose and sucrose in the concentration range from 5 mg mL-1 to 100 mg mL-1 in several beverages. The results obtained with the EC-QCL detector were found to be in good agreement with those obtained using a differential refractive index detector as a reference. The standard deviation of the method for the linear calibration was better than 5 mg mL-1 for all sugars and reached a minimum of 1.9 mg mL-1, while the DRI detector reached a minimum of 1 mg mL-1. Besides the quantification of sugars for which a calibration was performed, also chromatographic peaks of other components could be identified on the basis of their IR absorption spectra. This includes taurine, ethanol, and sorbitol. This journal is © the Partner Organisations 2014.


Perez-Guaita D.,University of Valencia | Kuligowski J.,University of Valencia | Quintas G.,Leitat Technological Center | Garrigues S.,University of Valencia | Guardia M.d.l.,University of Valencia
Talanta | Year: 2013

Locally weighted partial least squares regression (LW-PLSR) has been applied to the determination of four clinical parameters in human serum samples (total protein, triglyceride, glucose and urea contents) by Fourier transform infrared (FTIR) spectroscopy. Classical LW-PLSR models were constructed using different spectral regions. For the selection of parameters by LW-PLSR modeling, a multi-parametric study was carried out employing the minimum root-mean square error of cross validation (RMSCV) as objective function. In order to overcome the effect of strong matrix interferences on the predictive accuracy of LW-PLSR models, this work focuses on sample selection. Accordingly, a novel strategy for the development of local models is proposed. It was based on the use of: (i) principal component analysis (PCA) performed on an analyte specific spectral region for identifying most similar sample spectra and (ii) partial least squares regression (PLSR) constructed using the whole spectrum. Results found by using this strategy were compared to those provided by PLSR using the same spectral intervals as for LW-PLSR. Prediction errors found by both, classical and modified LW-PLSR improved those obtained by PLSR. Hence, both proposed approaches were useful for the determination of analytes present in a complex matrix as in the case of human serum samples. © 2013 Elsevier B.V. All rights reserved.


Kuligowski J.,University of Valencia | Quintas G.,Leitat Technological Center | Herwig C.,Vienna University of Technology | Lendl B.,Vienna University of Technology
Talanta | Year: 2012

This paper shows the ease of application and usefulness of mid-IR measurements for the investigation of orthogonal cell states on the example of the analysis of Pichia pastoris cells. A rapid method for the discrimination of entire yeast cells grown under carbon and nitrogen-limited conditions based on the direct acquisition of mid-IR spectra and partial least squares discriminant analysis (PLS-DA) is described. The obtained PLS-DA model was extensively validated employing two different validation strategies: (i) statistical validation employing a method based on permutation testing and (ii) external validation splitting the available data into two independent sub-sets. The Variable Importance in Projection scores of the PLS-DA model provided deeper insight into the differences between the two investigated states. Hence, we demonstrate the feasibility of a method which uses IR spectra from intact cells that may be employed in a second step as an in-line tool in process development and process control along Quality by Design principles. © 2012 Elsevier B.V.


Kuligowski J.,University of Valencia | Quintas G.,Leitat Technological Center | Tauler R.,CSIC - Institute of Chemical and Environmental Research | Lendl B.,Vienna University of Technology | De La Guardia M.,University of Valencia
Analytical Chemistry | Year: 2011

The use of multivariate curve resolution-alternating least-squares (MCR-ALS) in liquid chromatography-infrared detection (LC-IR) is troublesome due to the intense background absorption changes during gradient elution. Its use has been facilitated by previous removal of a significant part of the solvent background IR contributions due to common mobile phase systems employed during reversed phase gradient applications. Two straightforward background correction approaches based on simple-to-use interactive self-modeling mixture analysis (SIMPLISMA) and principal component analysis (PCA) are proposed and evaluated on reversed phase gradient LC-IR data sets obtained during the analysis of carbohydrate and nitrophenol mixtures. After subtraction of the calculated background signal, MCR-ALS provided improved signal-to-noise ratios, removed remaining mobile phase and background signal contributions, and resolved overlapping chromatographic peaks. The present approach tends to enable easy-to-use background correction to facilitate the use of MCR-ALS in online LC-IR, even in challenging situations when gradient conditions are employed and only poor chromatographic resolution is achieved. It, therefore, shows great potential to facilitate the full exploitation of the advantages of simultaneous quantification and identification of a vast amount of analytes employing online IR detection, making new exciting applications more accessible. © 2011 American Chemical Society.


Salvans S.,Hospital del Mar | Salvans S.,Colorectal Cancer Research Group | Mayol X.,Colorectal Cancer Research Group | Alonso S.,Hospital del Mar | And 9 more authors.
Annals of Surgery | Year: 2014

Objective: The aim of this study was to investigate the effect of postoperative peritoneal infection on proliferation, migration, and invasion capacities of cancer cells lines in vitro after surgery for colorectal cancer. Background: Anastomotic leakage is associated with higher rates of recurrence after surgery for colorectal cancer. However, the mechanisms responsible are unknown. We hypothesized that the infection-induced inflammatory response may enhance tumor progression features of residual cancer cells. Methods: Prospective matched cohort study. Patients undergoing surgery for colorectal cancer with curative intent (January 2008-March 2012) were included. Patients who had an anastomotic leak or intra-abdominal abscess were included in the infection group (n = 47). For each case patient, another patient with an uncomplicated postoperative course was selected for the control group (n = 47). In vitro treatments on cancer cell lines (MDA-MB-231 and SW620) were performed using baseline and postoperative serumand peritoneal fluid samples to determine cell proliferation and cell migration/invasion activities. Results: Postoperative peritoneal fluid from infected patients enhanced both cell migration (infection: 140 ± 85 vs control: 94 ± 30; P = 0.016) and cell invasion (infection: 117 ± 31 vs control: 103 ± 16; P = 0.024) capacities of cancer cell lines.With serum samples, these effects were only observed in cell migration assays (infection: 98 ± 28 vs control: 87 ± 17; P = 0.005). Some minor activation of cell proliferation was observed by treatment with serum from infection group. Two-year cumulative disease-free survival was significantly lower in patients with postoperative peritoneal infection (infection: 77.6% vs control: 90.6%; P = 0.032). Conclusions: Our results suggest that postoperative peritoneal infection enhances the invasive capacity of residual tumor cells after surgery, thus facilitating their growth to recurrent tumors. Copyright © 2014 by Lippincott Williams & Wilkins.


Camara R.M.,Technical University of Madrid | Crespo E.,Leitat Technological Center | Portela R.,ICP | Suarez S.,CIEMAT | And 3 more authors.
Catalysis Today | Year: 2014

Organic polymers are excellent substrates for photocatalytic applications of TiO2 thin films, which can be easily prepared by sol-gel synthesis followed by dip coating. However, the wettability of the hydrophobic surface of polymers should be improved. In this work, commercial poly(vinyl chloride) (PVC), poly(methyl methacrylate) (PMMA) and polystyrene (PS) were selected according to their high transmittance in the TiO2 activation range for the immobilization of the semiconductor. Low pressure (LPP) and atmospheric pressure (APP) plasma were used to modify the surface properties of the organic polymers to improve the affinity for TiO2 aqueous sols and solutions. The characterization of the materials was performed by atomic force microscopy (AFM), UV-Vis spectroscopy, and contact angle and surface tension measurements, employed to evaluate wettability of the samples. The effect of the power of discharge and treatment time on the induced surface properties was analyzed. LPP at 300 W during 600 s was found as adequate treatment to promote the hydrophilicity of all samples without damage to the bulk. The adhesion of TiO2 thin films on the polymers was improved with the plasma pre-treatment due to the generation of roughness and specific polar functional groups. Accordingly, the photocatalytic performance increased with respect to the non-treated substrates, reaching similar conversion values than the reference photocatalyst where glass, a hydrophilyc substrate, was used as support. © 2013 Elsevier B.V.


Kenzaoui B.H.,University of Lausanne | Vila M.R.,Leitat Technological Center | Miquel J.M.,Leitat Technological Center | Cengelli F.,University of Lausanne | Juillerat-Jeanneret L.,University of Lausanne
International Journal of Nanomedicine | Year: 2012

Nanoparticles (NPs) are in clinical use or under development for therapeutic imaging and drug delivery. However, relatively little information exists concerning the uptake and transport of NPs across human colon cell layers, or their potential to invade three-dimensional models of human colon cells that better mimic the tissue structures of normal and tumoral colon. In order to gain such information, the interactions of biocompatible ultrasmall superparamagnetic iron oxide nanoparticles (USPIO NPs) (iron oxide core 9-10 nm) coated with either cationic polyvinylamine (aminoPVA) or anionic oleic acid with human HT-29 and Caco-2 colon cells was determined. The uptake of the cationic USPIO NPs was much higher than the uptake of the anionic USPIO NPs. The intracellular localization of aminoPVA USPIO NPs was confirmed in HT-29 cells by transmission electron microscopy that detected the iron oxide core. AminoPVA USPIO NPs invaded three-dimensional spheroids of both HT-29 and Caco-2 cells, whereas oleic acid-coated USPIO NPs could only invade Caco-2 spheroids. Neither cationic aminoPVA USPIO NPs nor anionic oleic acid-coated USPIO NPs were transported at detectable levels across the tight CacoReady™ intestinal barrier model or the more permeable mucus-secreting CacoGoblet™ model. © 2012 Halamoda Kenzaoui et al, publisher and licensee Dove Medical Press Ltd.

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