Nuestros investigadores

Mortars with two different binders (Portland cement (PC) and high alumina cement (HAC)) were modified upon the bulk incorporation of nano-structured photocatalytic additives (bare TiO2, and TiO2 doped with either iron (Fe-TiO2) or vanadium (V-TiO2)). Plastic and hardened state properties of these mortars were assessed in order to study the influence of these nano-additives. Water demand was increased, slightly by bare TiO2 and Fe-TiO2, and strongly by V-TiO2, in agreement with the reduction of the particle size and the tendency to agglomerate. Isothermal calorimetry showed that hydration of the cementitious matrices was accelerated due to additional nucleation sites offered by the nano-additives. TiO2 and doped TiO2 did not show pozzolanic reactivity in the binding systems. Changes in the pore size distribution, mainly the filler effect of the nano-additives, accounted for the increase in compressive strengths measured for HAC mortars. A complex microstructure was seen in calcium aluminate cement mortars, strongly dependent on the curing conditions. Fe-TiO2 was found to be homogeneously distributed whereas the tendency of V-TiO2 to agglomerate was evidenced by elemental distribution maps. Water absorption capacity was not affected by the nano-additive incorporation in HAC mortars, which is a favourable feature for the application of these mortars.

Our data demonstrate that AAV8-AAT-ATP7B-mediated gene therapy provides long-term correction of copper metabolism in a clinically relevant animal model of WD providing support for future translational studies.

Polynaphtalenesulfonate (PNS) and lignosulfonate (LS) were tested as superplasticizers in pastes and mortars of pure air lime and air lime with a pozzolanic additive, nanosilica (NS). LS showed a better plasticizing effect than PNS: the flowability of the samples with LS as well as the slump retention over time was larger. LS strongly hindered carbonation due to its ability to form Ca2+ complexes. In mortars with NS, PNS was seen to interfere with the C-S-H formation, resulting in lower mechanical strengths. Adsorption isotherms and zeta potential showed that PNS was more adsorbed than LS onto lime and C-S-H particles. PNS acted mainly through electrostatic repulsion owing to its high anionic charge density and flat adsorption. However, LS was more efficient as superplasticizer in air lime media, steric hindrance being the main mechanism responsible for avoiding flocculation. Furthermore, LS yielded high compressive strengths in mortars with NS.

Photocatalytic activity of TiO2 was studied in two types of calcium aluminate cement (CAC) under two different curing regimes. The effect of the TiO2 addition on the setting time, consistency and mechanical properties of the CACs was evaluated. The abatement of gaseous pollutants (NOx) under UV irradiation was also assessed. These cementitious matrices were found to successfully retain NO2: more abundant presence of aluminates in white cement (w-CAC, iron-lean) helped to better adsorb NO2, thus improving the conversion performance of the catalyst resulting in a larger NOx removal under UV irradiation. As evidenced by XRD, SEM, EDAX and zeta potential analyses, the presence of ferrite in dark cement (d-CAC, iron-reach) induced a certain chemical interaction with TiO2. The experimental findings suggest the formation of new iron titanate phases, namely pseudobrookite. The reduced band-gap energy of these compounds compared with that of TiO2 accounts for the photocatalytic activity of these samples.

Oxaliplatin (L-OH), a platinum derivative with good tolerability is currently combined with Cetuximab (CTX), a monoclonal antibody (mAb), for the treatment of certain (wild-type KRAS) metastatic colorectal cancer (CRC) expressing epidermal growth factor receptor (EGFR). Improvement of L-OH pharmacokinetics (PK) can be provided by its encapsulation into liposomes, allowing a more selective accumulation and delivery to the tumor. Here, we aim to associate both agents in a novel liposomal targeted therapy by linking CTX to the drug-loaded liposomes. These EGFR-targeted liposomes potentially combine the therapeutic activity and selectivity of CTX with tumor-cell delivery of L-OH in a single therapeutic approach. L-OH liposomes carrying whole CTX or CTX-Fab¿ fragments on their surface were designed and characterized. Their functionality was tested in vitro using four human CRC cell lines, expressing different levels of EGFR to investigate the role of CTX-EGFR interactions in the cellular binding and uptake of the nanocarriers and encapsulated drug. Next, those formulations were evaluated in vivo in a colorectal cancer xenograft model with regard to tumor drug accumulation, toxicity and therapeutic activity. In EGFR-overexpressing cell lines, intracellular drug delivery by targeted liposomes increased with receptor density reaching up to 3-fold higher levels than with non-targeted liposomes. Receptor specific uptake was demonstrated by competition with free CTX, which reduced...

Topical therapy is the ideal outpatient treatment of cutaneous leishmaniasis (CL) because of the ease of administration and lower cost. It could be suitable as monotherapy for localized cutaneous leishmaniasis (LCL) or in combination with systemic therapies for more severe forms of the disease. Although paromomycin (PM) ointment can be recommended for the treatment of LCL caused by Leishmaniamajor, a more effective topical treatment should be achieved regarding the physicochemical properties of this aminoglucoside and its rather poor intrinsic antileishmanial activity, that hampers the accumulation of enough amount of drug in the dermis (where the infected macrophages home) to exert its activity. In this work, we determined a 50% effective dose of 5.6 ¿M for a novel compound, bis-4-aminophenyldiselenide, against L. major intracellular amastigotes. This compound and PM were formulated in chitosan hydrogels and ex vivo permeation and retention studies in the different skin layers were performed with pig ear skin in Franz diffusion cells. The results showed that less than 2¿4% of the diselenide drug penetrated and permeated through the skin. In contrast, the percentage of PM penetration was about 25¿60% without important retention in the skin. When topically applied to lesions of L. major infected BALB/c mice, the novel diselenide chitosan formulation was unable to slow lesion progression and reduce parasite burden. Considerations during the process of novel drug development and

The aim of this study was to investigate the potential modulators of erythrocyte glutathione peroxidase (GPx) activity in young and apparently healthy individuals. One hundred one individuals (53 women and 48 men) were evaluated for anthropometric measurements, biochemical markers, clinical, dietary, and endogenous and exogenous components of the antioxidant defense system. Statistical analysis was performed to detect differences among subjects by the median of GPx activity. A linear regression model and Spearman correlation coefficients were used to screen the associations between GPx activity and interest variables. Individuals with higher GPx enzymatic activity were older and higher circulating levels of oxidized low-density lipoprotein (ox-LDL) values, but conversely lower nail concentrations of selenium and copper (P<0.05). The GPx activity was positively correlated to truncal fat percentage values (r=0.24, P=0.016), circulating levels of ox-LDL (r=0.28, P=0.004), and daily vitamin C intake (r=0.28, P=0.007), and negatively correlated to the nail concentration of selenium (r=-0.24, P=0.026). Interesting, it was noticed that the truncal fat percentage and circulating levels of ox-LDL explained 5.9 and 7.4% of the GPx enzymatic activity. Thus, preventive measures such as adequate antioxidant intake and proper fat percentage would be a priority in the nutritional care of young and apparently healthy individuals.

The oxidative stability of seven oils with different fatty acid profiles was assessed. Oxidation at 0, 2 and 4 h at 180 °C was monitored by measuring the absorbance of thiobarbituric acid reactive substances (TBARS) along the absorption spectrum (300¿600 nm), the volatile aldehydes (HS-SPME¿GC¿MS) and the fatty acid profile (FID-GC). TBARS absorption spectrum behavior depended on the lipid composition of heated oils. Higher absorbance increments during heating were noticed at 390 nm compared to 532 nm (from 2 to 21 fold higher depending on the oil), pointing to its better sensitivity to detect oxidation. Furthermore, a close relationship between ABS390, the loss of polyunsaturated fatty acids and their corresponding oxidation compounds (volatile aldehydes) was revealed by Principal Component Analysis. Multiparametric equations allowed predicting the formation of volatile aldehydes of heated oils by measuring only two parameters: TBARS390 during their heating, and the lipid profile in unheated oils (MUFA, ¿-3 and ¿-6). Results pointed out the interest of choosing ABS390 when the oxidative evolution of vegetable oils under heating is assessed by the TBARS test

Two polycarboxylate ether copolymers were assessed as superplasticizers (SPs) for hydrated lime pastes modified with two reactive compounds, nanosilica (NS) and ceramic metakaolin (MK). Characterization of the molecular structure of the SPs by Size Exclusion Chromatography, XRD, FTIR and MALDI-TOF (Matrix Assisted Laser Desorption Ionization Time-of-Flight) mass spectrometry was performed. The structures of the polymers were seen to be star- and worm-like shapes. A close relationship was found between the molecular architecture and the flowability of the pastes, being the star-shaped plasticizer the most efficient. Zeta potential assessment allowed us to elucidate a steric hindrance as the main action mechanism for these polymers. The large specific surface area of nanosilica led to a large SPs consumption as compared with metakaolin with lower surface area. However, SPs in MK¿lime samples were attached favourably on the C¿S¿H and aluminate hydrates, so that the dispersing action was greater with respect to NS¿lime suspensions.

Polyphosphate-modified calcium aluminate cement matrices were prepared by using aqueous solutions polluted with toxic metals as mixing water to obtain waste-containing solid blocks with improved management and disposal. Synthetically contaminated waters containing either Pb or Cu or Zn were incorporated into phosphoaluminate cement mortars and the effects of the metal¿s presence on setting time and mechanical performance were assessed. Sorption and leaching tests were also executed and both retention and release patterns were investigated. For all three metals, high uptake capacities as well as percentages of retention larger than 99.9% were measured. Both Pb and Cu were seen to be largely compatible with this cementitious matrix, rendering the obtained blocks suitable for landfilling or for building purposes. However, Zn spoilt the compressive strength values because of its reaction with hydrogen phosphate anions, hindering the development of the binding matrix.

BACKGROUND: A combined technological approach was applied in the development of healthier dry fermented sausages: a partial substitution of the pork back fat by pre-emulsified linseed oil and a partial replacement of sodium chloride with calcium ascorbate at two different levels, leading to low amounts of salt (14gSalt and 10gSalt, with 14 g and 10 g NaCl per kg of mixture, respectively). RESULTS: The developed products (14gSalt and 10gSalt) showed adequate results for aw (0.85 and 0.87) and pH (4.98 and 5.21), and low lipid oxidation values (1.4 x 104 and 1.5 x 105 g malondialdehyde (MDA) kg1). The lipid modification led to a significantly higher supply of -3 (23.3 g kg1) compared to the control (3.2 g kg1). Simultaneously, reductions of 38% and 50% in sodium content and a calcium supply of 4 and 5.2 g kg1 were achieved in the 14gSalt and 10gSalt formulations, respectively, compared to the control products (26 g salt and 0.87 g kg1 Ca). Instrumental analysis of colour and texture and sensory studies demonstrated that the organoleptic quality of the new formulations was similar to that of traditional products. CONCLUSIONS: The developed dry fermented sausages showed healthier properties than traditional ones owing to their reduced sodium and higher calcium content and a significant supply of -3 fatty acids. (c) 2012 Society of Chemical Industry

The effect of individual and combined addition of both nanosilica (NS) and polycarboxylate-ether plasticizer (PCE) admixtures on aerial lime mortars was studied. The sole incorporation of NS increased the water demand, as proved by the mini-spread flow test. An interaction between NS and hydrated lime particles was observed in fresh mixtures by means of particle size distribution studies, zeta potential measurements and optical microscopy, giving rise to agglomerates. On the other hand, the addition of PCE to a lime mortar increased the flowability and accelerated the setting process. PCE was shown to act in lime media as a deflocculating agent, reducing the particle size of the agglomerates through a steric hindrance mechanism. Mechanical strengths were improved in the presence of either NS or PCE, the optimum being attained in the combined presence of both admixtures that involved relevant microstructural modifications, as proved by pore size distributions and SEM observations.

Due to the fact that infants and children are especially sensitive to mercury and arsenic exposure, predominantly through diet, a strict control of the most widely consumed infant foods, especially infant cereals, is of paramount importance. Levels of both total mercury and arsenic in 91 different infant cereals from ten different manufacturers in Spain were determined by flow injection adapted to cold vapor and hydride generation atomic absorption spectrometry, respectively. Cereals were assessed in terms of the different types, the predominating cereal in the formulation, the added ingredients, and whether the cereal was organically or conventionally obtained. In general, the content of toxic elements (median (Q(1); Q(3))) found in infant cereals based on conventionally obtained raw materials (n = 74, Hg: 2.11 (0.42; 4.58), As: 21.0 (9.4; 50.9) mu g Kg(-1)) was lower than in cereals produced by organic methods (n = 17, Hg: 5.48 (4.54; 7.64), As: 96.3 (87.5; 152.3) mu g Kg(-1)). Mercury content in infant cereals shows the higher values in those formulations with ingredients susceptible to particulate contamination such as gluten-free or cacao-based cereals. The highest arsenic content appears in the rice-based cereals. The mercury and the inorganic arsenic dietary intakes for infants fed on the infant cereals studied were assessed, taking into account the different stages of growth. Organic infant cereals based on cocoa showed the highest risk intakes of mercury, very close to exceeding the intake reference. Just the opposite, 95% of the organically produced infant cereals and 70% of the conventional gluten-free infant cereals showed an inadmissible risk of arsenic intake. Thus, it seems prudent to call for continued efforts in standardizing routine quality control and in reducing arsenic levels in infant cereals; in addition it is essential that relevant legislation be established and regulated by EC regarding these two toxic elements.

The effect of storage temperature (65 degrees C, 48 h) on the oxidative stability of a food-grade water-in-oil-in-water (W/O/W) emulsion was studied by comparison with an oil-in-water (O/W) emulsion. The emulsions were prepared with linseed oil or olive oil, and in each case, two antioxidants were evaluated, an aqueous Melissa lyophilized extract and BHA. Emulsions were characterized using bright field light microscopy and the oxidation was monitored by measuring the lipid hydroperoxides, thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and trienes (CT), alpha-tocopherol and Lipophilic Oxygen Radical Absorbance Capacity (L-ORACFL) Assay. A great stability of olive oil emulsions was observed, without noticing differences between antioxidants or type of emulsion. This behavior was not observed in linseed oil emulsions. In this case the lipophilic antioxidant (BHA) seemed to be more efficient delaying the lipid oxidation in W/O/W emulsions than the water Melissa extract while the opposite occurs in the O/W emulsion. The type of antioxidant is a key factor in controlling oxidation in W/O/W and O/W emulsions which are prepared with highly polyunsaturated oils, but not in the case of highly monounsaturated ones.

Lead and cadmium have become highly toxic metallic elements. There is an obvious toxicological impact of these elements on infants since their intestinal absorption is significantly higher than in adults, thus it is desirable to quantify lead and cadmium levels in commonly consumed infant foods. Zeeman background correction, transversely-heated graphite furnace atomic absorption spectrometry, was used to determine both the lead and cadmium content of 91 Spanish infant cereals. Cereals were assessed in terms of different types, cereal predominant in formulation and whether it was obtained organically or conventionally. Preliminary analysis revealed a noticeably higher content of lead and cadmium (median, Q1-Q3) in organic cereals (n = 17, Pb: 26.07; 21.36-51.63; Cd: 18.52; 16.56-28.50 mu g kg(-1)) in relation to conventional ones (n = 74, Pb: 10.78; 6.43-19.33; Cd: 7.12; 4.40-11.77 mu g kg(-1)). Three formulations exceeded European lead maximum levels. Added ingredients (milk, cocoa, fruit and honey) to the cereal base provide lead enrichment. For cadmium, this pattern was observed by cereal based on cocoa, but also the raw materials contributed with a dilution phenomenon, decreasing the final cadmium concentration in infant cereal. Apart from several organically produced cereals, lead content showed a narrow variation, where gluten-free cereals provide lower cadmium content than formulations containing gluten. Dietary intakes of both elements were assessed in comparison with the reference intake values proposed by the EFSA Panel on Contaminants in the Food Chain. Organic infant cereals based on honey and cocoa supplied the highest risk intakes of lead and cadmium, respectively. In accordance with the actual state of knowledge on lead and cadmium toxicity and attending to the upper limits calculated from risk intake values set by EFSA, it seems prudent to call for a revision of both heavy metals content regulated by EC to set a maximum guideline values for infant cereal at 55 and 45 mu g kg(-1), respectively.

Cement mortars loaded with Cr, Pb and Zn were modified by polymeric admixtures [chitosans with low (LMWCH), medium (MMWCH) and high (HMWCH) molecular weight and hydroxypropylchitosan (HPCH)]. The influence of the simultaneous presence of the heavy metal and the polymeric additive on the fresh properties (consistency, water retention and setting time) and on the compressive strength of the mortars was assessed. Leaching patterns as well as properties of the cement mortars were related to the heavy metals-bearing solid phases. Chitosan admixtures lessened the effect of the addition of Cr and Pb on the setting time. In all instances, chitosans improved the compressive strength of the Zn-bearing mortars yielding values as high as 15 N mm¿2. A newly reported Zn phase, dietrichite (ZnAl2(SO4)4·22H2O) was identified under the presence of LMWCH: it was responsible for an improvement by 24% in Zn retention. Lead-bearing silicates, such as plumalsite (Pb4Al2(SiO3)7), were also identified by XRD confirming that Pb was mainly retained as a part of the silicate network after Ca ion exchange. Also, the presence of polymer induced the appearance and stabilization of some Pb(IV) species. Finally, diverse chromate species were identified and related to the larger leaching values of Cr(VI).

The incidence of aflatoxin M-1 (AFM(1)) in 69 different infant formulae marketed in Spain between 2007 and 2008 was studied and dietary intake estimated. Samples were analysed using an HPLC method coupled with fluorescence detection after immunoaffinity column clean-up. The toxin was detected in 26 formulae (37.7%) at levels below the permissible limit set by EC legislation, giving a range of 0.6-11.6 ng kg(-1) with a mean value of 3.1 ng kg(-1). Increasing occurrence was found in those formulae produced by the less complex manufacturing processes affecting casein/whey protein ratio: pre-term, 14.3%; starter, 35.3%; follow-up, 42.1%; toddler 87.6%; while hypoallergenic and lactose-free were totally exempt. Additionally, the influence of main protein source and physical state (powdered and ready-to-use formula) on AFM(1) occurrence was evaluated leading to similar conclusions. Dietary AFM1 weekly intake was observed to be stable around 1 ng kg(-1) bw for standard formula and 0.1 ng kg(-1) bw for pre-term feeding.

Biodegradable poly (lactic-co-glycolic) acid (PLGA) nanoparticles incorporating cisplatin have been developed to evaluate its in vivo efficacy in tumor-bearing mice. In vitro Study proved two mechanisms of action for cisplatin depending on the dose and the rate at which this dose is delivered. In vivo study, 5 mg/kg of cisplatin nanoparticles administered to mice, exhibited a tumour inhibition similar to free cisplatin, although the area under cisplatin concentration-time Curve between 0 and 21 days (AUC(0-21)) had lower Value for the formulation than for drug solution (P < 0.05). This result was associated with a higher activation of apoptosis in tumor, mediated by caspase-3, after nanoparticles administration. Toxicity measured as the change in body weight, and blood urea nitrogen (BUN) plasma levels showed that cisplatin nanoparticles treatment did not induce significant changes in both parameters compared to control, while for free drug, a statistical (P < 0.01) increase was observed. In addition, a good correlation was found between time profiles of tumor volume and vascular endothelial growth factor (VEGF) plasma levels, suggesting that its expression could help to follow the efficacy of the treatment. Therefore, the PLGA nanoparticles seem to provide a promising carrier for cisplatin administration avoiding its side effects without a reduction of the efficacy, which was consistent with a higher activation of apoptosis than free drug.

Aflatoxins (AFB1, AFB2, AFG1 and AFG2) are immunosuppressant, mutagenic, teratogenic and carcinogenic agents with a widespread presence in foodstuffs. Since human exposure to aflatoxins occurs primarily by contaminated food intake, and given the greater susceptibility of infants to their adverse effects, the quantification of these mycotoxins in infant food based on cereals is of relevance. Aflatoxin levels were determined in 91 Spanish infant cereals classified in terms of non- and organically produced and several types from 10 different manufacturers, using a extraction procedure followed by inmunoaffinity column clean-up step and HPLC with fluorescence detection (FLD) and post-column derivatisation (Kobra Cell system). Daily aflatoxin intake was also assessed. Preliminary analysis showed a valuable incidence of detected infant cereal samples at an upper concentration level than the detection limit for total aflatoxin (66%), corresponding to a 46, 40, 34 and 11% for AFB1, AFB2, AFG1 and AFG2, respectively. Lower aflatoxin values (median, Q1, Q3) in conventional infant cereal (n = 74, AFB1: LOD (n.d.; 0.02), AFB2: n.d. (n.d.; 0.01), AFG1: LOD (n.d.; 0.004), and AFG2: n.d. (n.d.; LOD) and total AF (AFtotal): 0.01 (LOD; 0.04 mu g kg-1) in comparison with infant cereal ecologically produced (n = 17, AFB1: 0.02 (0.02; 0.21), AFB2: n.d. (n.d.; 0.03), AFG1: 0.02 (0.01; 0.05), and AFG2: 0.007 (n.d.; 0.02) and AFtotal: 0.05 (0.03; 0.31 mu g kg-1) were found. In addition, five organic formulations (3.11, 1.98, 0.94, 0.47 and 0.21 mu g kg-1) exceeded European AFB1 legislation (0.10 mu g kg-1) versus two conventional cereals (0.35 and 0.12 mu g kg-1). According to the type of infant cereal, those with cocoa had the highest aflatoxin levels. Gluten-free and cereals with dehydrated fruits had an intermediate level and milk- or honey-based cereals and multi-cereals contained the lowest levels. With the exception of the non-compliant cocoa-based organic formulation, none of the infant cereals analyzed gave a higher intake of 1 ng kg-1 body weight per day, suggesting that infants fed on infant cereals are exposed to a low health hazard. Nevertheless, manufacturers are advised for continued efforts in routine monitoring and a more careful selection of raw material to minimize aflatoxin levels in these infant foods.

The obtaining of self-cleaning mortars is very interesting to apply them in Built Heritage. Atmospheric pollutants, mainly carbonaceous particles and gases like NOx and SO2 can lead to severe aesthetic and functional damages in artworks. In the case of mortars and renders, the use of photocatalysts -usually based on TiO2- can be worthy of consideration. Photocatalysts, after being activated by light, are able to oxidize pollutants avoiding their deposition onto building materials. In this work, different air lime mortars modified upon the addition of TiO2-based photocatalysts were obtained and studied. Photocatalysts can be incorporated in bulk and the changes in fresh state properties were studied as well as the effect of the presence of the photocatalysts on the pore structure and mechanical resistance. Finally, the photocatalytic efficiency of these materials was carried out by means of a NOx abatement test. Results showed that the presence of the photocatalysts had a positive impact on the preservation of the lime mortars characteristics.

This contribution dealt with the design of different air lime mortars and pastes by combining a nanostructured pozzolanic additive, nanosilica, and different dispersing agents, superplasticizers (two different polycarboxylate ethers (PCE), a polynaphthalene sulfonate-based polymer (PNS) and a lignosulfonate (LS)). In pure air lime systems, the highest effectiveness was shown by the PCE1, whereas the PNS was the less effective superplasticizer. In samples with nanosilica, the PCE1 was also the most effective superplasticizer. LS was seen to be effective at low dosages. In the presence of the pozzolanic additive, there was a high consumption of polycarboxylates. Nanosilica provided no ¿active¿ adsorption sites, resulting in a slight decrease of the zeta potential values. PCE1 showed low adsorbed amounts, better dispersing action and required lower dosage of plasticizing agent. There was a positive combination between lime mortars with nanosilica and polycarboxylates, which resulted in a mechanical strength improvement. Also the combined presence of nanosilica, for example, with PNS or with LS yielded better compressive strengths, being LS more effective than PNS: SEM images showed the better formation of C-S-H phases in LS-mortars.

The rationale is that polyphosphate-CAC matrices have shown interesting potential to solidify/stabilize heavy metals, owing to the aforementioned acid-base reaction that yields a compact and low porous matrix mainly composed of ACP - amorphous calcium phosphate -, which can be able to retain hazardous compounds. We aimed to take advantage of the reactivity of one of the sludge components: the sludges with relatively large concentrations of phosphate are expected to act themselves as reactants that, interacting with the CAC, could result in a very effective retaining system of the sludge constituents. Sludge samples from two locations have been incorporated in high proportion within the mix. We discussed the effects of the sludge on the CAC mortar and a possible interaction mechanism is provided.