Cytotoxicity of CeO2 nanoparticles using in vitro assay with Mytilus galloprovincialis hemocytes: Relevance of zeta potential, shape and biocorona formation.

Over the last decades, the growth in nanotechnology has provoked an increase in the number of its applications and consumer products that incorporate nanomaterials in their formulation. Metal nanoparticles are released to the marine environment and they can interact with cells by colloids forces establish a nano-bio interface. This interface can be compatible or generate bioadverse effects to cells. The daily use of CeO2 nanoparticles (CeO2 NPs) in industrial catalysis, sunscreen, fuel cells, fuel additives and biomedicine and their potential release into aquatic environments has turned them into a new emerging pollutant of concern. It is necessary to assess of effects of CeO2 NPs in aquatic organisms and understand the potential mechanisms of action of CeO2 NP toxicity to improve our knowledge about the intrinsic and extrinsic characteristic of CeO2 NPs and the interaction of CeO2 NPs with biomolecules in different environment and biological fluids. The conserved innate immune system of bivalves represents a useful tool for studying immunoregulatory responses when cells are exposed to NPs. In this context, the effects of two different CeO2 NPs with different physico-chemical characteristics (size, shape, zeta potential and Ce+3/Ce+4 ratio) and different behavior with biomolecules in plasma fluid were studied in a series of in vitro assays using primary hemocytes from Mytilus galloprovincialis. Different cellular responses such as lysosome membrane stability, phagocytosis capacity and extracellular reactive oxygen species (ROS) production were evaluated. Our results indicate that the agglomeration state of CeO2 NPs in the exposure media did not appear to have a substantial role in particle effects, while differences in shape, zeta potential and biocorona formation in NPs appear to be important in provoking negative impacts on hemocytes. The negative charge and the rounded shape of CeO2 NPs, which formed Cu, Zn-SOD biocorona in hemolymph serum (HS), triggered higher changes in the biomarker of stress (LMS) and immunological parameters (ROS and phagocytosis capacity). On the other hand, the almost neutral surface charge and well-faceted shape of CeO2 NPs did not show either biocorona formation in HS under tested conditions or significant responses. According to the results, the most relevant conclusion of this work is that not only the physicochemical characterization of CeO2 NPs plays an important role in NPs toxicity but also the study of the interaction of NPs with biological fluids is essential to know it behavior and toxicity at cellular level.

Toxicity of TiO2, in nanoparticle or bulk form to freshwater and marine microalgae under visible light and UV-A radiation.

Use of titanium dioxide nanoparticles (TiO2 NPs) has become a part of our daily life and the high environmental concentrations predicted to accumulate in aquatic ecosystems are cause for concern. Although TiO2 has only limited reactivity, at the nanoscale level its physico-chemical properties and toxicity are different compared with bulk material. Phytoplankton is a key trophic level in fresh and marine ecosystems, and the toxicity provoked by these nanoparticles can affect the structure and functioning of ecosystems. Two microalgae species, one freshwater (Chlamydomonas reinhardtii) and the other marine (Phaeodactylum tricornutum), have been selected for testing the toxicity of TiO2 in NP and conventional bulk form and, given its photo-catalytic properties, the effect of UV-A was also checked. Growth inhibition, quantum yield reduction, increase of intracellular ROS production, membrane cell damage and production of exo-polymeric substances (EPS) were selected as variables to measure. TiO2 NPs and bulk TiO2 show a relationship between the size of agglomerates and time in freshwater and saltwater, but not in ultrapure water. Under two treatments, UV-A (6 h per day) and no UV-A exposure, NPs triggered stronger cytotoxic responses than bulk material. TiO2 NPs were also associated with greater production of reactive oxygen species and damage to membrane. However, microalgae exposed to TiO2 NPs and bulk TiO2 under UV-A were found to be more sensitive than in the visible light condition. The marine species (P. tricornutum) was more sensitive than the freshwater species, and higher Ti internalization was measured. Exopolymeric substances (EPS) were released from microalgae in the culture media, in the presence of TiO2 in both forms. This may be a possible defense mechanism by these cells, which would enhance processes of homoagglomeration and settling, and thus reduce bioavailability.

Direct and indirect effects of silver nanoparticles on freshwater and marine microalgae (Chlamydomonas reinhardtii and Phaeodactylum tricornutum).

The last decade has seen a considerable increase in the use of silver nanoparticles (AgNPs), which are found in many every-day consumer products including textiles, plastics, cosmetics, household sprays and paints. The release of those AgNPs into aquatic environments could be causing ecological damage. In this study we assess the toxicity of AgNPs of different sizes to two species of microalgae, from freshwater and marine environment (Chlamydomonas reinhardtii and Phaeodactylum tricornutum respectively). Dissolution processes affect the form and concentration of AgNPs in both environments. Dissolution of Ag from AgNPs was around 25 times higher in marine water. Nevertheless, dissolution of AgNPs in both culture media seems to be related to the small size and higher surface area of NPs. In marine water, the main chemical species were AgCl2- (53.7%) and AgCl3-2 (45.2%). In contrast, for freshwater, the main chemical species were Ag+ (26.7%) and AgCl- (4.3%). The assessment of toxicological responses, specifically growth, cell size, cell complexity, chlorophyll a, reactive oxygen species, cell membrane damage and effective quantum yield of PSII, corroborated the existence of different toxicity mechanisms for microalgae. Indirect effects, notably dissolved Ag ions, seem to control toxicity to freshwater microalgae, whereas direct effects, notably attachment onto the cell surface and the internalization of AgNPs inside cells, seem to determine toxicity to the marine species studied. This research contributes to knowledge on the role of intrinsic and extrinsic factors in determining the behavior of NPs in different aquatic environments and the interaction with microalgae.

Homoagglomeration and heteroagglomeration of TiO2, in nanoparticle and bulk form, onto freshwater and marine microalgae.

TiO2 nanoparticles (TiO2 NPs) are employed in many products (paints, personal care products, especially sunscreens, plastics, paper, water potabilization and food products) and are then released into the environment from these products. These nanoparticles present potential risk to freshwater and marine microalgae. The primary toxicity mechanism is adsorption between NPs and microalgae (heteroagglomeration); however, studies of interactions of this kind are scarce. We investigated the heteroagglomeration process that occurs between two forms of TiO2 material, nanoparticles and bulk, and three different microalgae species, and under different environmental conditions (freshwater and marine water), in order to assess the influence of pH and ionic strength (IS). The heteroagglomeration process was examined by means of co-settling experiments and the Derjaguin-Landau-Verwey-Overbeek (DLVO) approach. The homoagglomeration process (only NPs to NPs) did not show differences between culture media (freshwater and marine water). However, in the heteroagglomeration process between NPs and cells, IS played an important role. Ions can compress the electro-double layer between NPs and microalgae, allowing a heteroagglomeration process to take place, as shown by settling experiments. TiO2 NPs presented a settling rate higher than bulk TiO2. The DLVO theory could only partially explain heteroagglomeration because, in this model, it is not considered that NP-NP and Cell-Cell homoagglomeration co-occur. In this study neither the role of exopolymeric substances in the interaction between NPs and cells nor detoxification are considered. The authors suggest that the interaction between NPs and microalgae could be considered as the first stage in the process by which nanoparticles affect microalgae.

CeO2 NPs, toxic or protective to phytoplankton? Charge of nanoparticles and cell wall as factors which cause changes in cell complexity.

CeO2 nanoparticles (CeO2 NPs) are well-known for their catalytic properties and antioxidant potential. Recent uses in therapy are based on the Ce+3 ions released by CeO2 NPs. Reactions involving redox cycles between Ce+3 and Ce+4 oxidation stage seem to promote scavenging of reactive oxygen species (ROS), thus protecting cells from oxygen damage. However, the internalization of CeO2 NPs and release of Ce+3 could be responsible for a toxic effect on cells. The literature reports controversial results on the toxicity of CeO2 NPs to phytoplankton. Therefore, we have tested the potential toxic effect of two CeO2 NPs (with positive and negative zeta potential) and bulk CeO2 (at 0.1, 1, 10, 100 and 200mg·L-1) on three species of microalgae from different environments: marine diatom (Phaeodactylum tricornutum), marine chlorophyte (Nannochloris atomus) and freshwater chlorophyte (Chlamydomonas reinhardtii) over 72h in batch cultures. Responses measured in the microalgae population are: growth, chlorophyll a, cell size, cell complexity, percentage of ROS, and percentage of cell membrane damage. Positive zeta potential CeO2 NPs provoked greater cell complexity (up to 78, 172 and 23 times more cell complexity than in controls found for C. reinhardtii, P. tricornutum and N. atomus respectively) than negative zeta potential CeO2 NPs. The SSC signal detected by flow cytometry measured increases of particles entering cells, and this is related to cell viability and levels of intracellular ROS (correlation between SSC and percentage of ROS of 0.72 and 0.97 found for C. reinhardtii and P. tricornutum). When increased cellular complexity over controls is between 2 and 6 times greater, CeO2 (in bulk or nanoparticulate form) seems to protect against ROS. When increased cellular complexity is from 7 to 23 times greater, CeO2 does not provoke toxic responses; however, when increased cellular complexity over controls is very high, from 61 to 172 times, increased ROS production and toxic responses are found. Results show that two factors, the charge of CeO2 NPs and cell wall structure, constitute the primary barrier to the possible accumulation of CeO2 NPs within phytoplankton cytosol.

Temporal and spatial assessment of microbial communities in commercial silages from bunker silos.

Ensiling is a feed preservation method of moist forage crops that generally depends on naturally developing lactic acid bacteria to convert water-soluble carbohydrates into organic acids. While bacterial community dynamics have been previously assessed in bench-scale and pilot ensiling facilities, almost no studies have assessed the microbiomes of large-scale silage facilities. This study analyzed bacterial community composition in mature silage from bunker silos in three commercial production centers as related to pH, organic matter, volatile fatty acid composition, and spatial distribution within the ensiling bunker. It revealed significant physicochemical differences between "preserved" regions situated in the center and along the walls of the silage bunkers that were characterized by high concentrations of lactic acid and other volatiles and pH values below 5, and "spoiled" regions in the corners (shoulders) of the bunkers that had low lactic acid concentrations and high pH values. Preserved silage was dominated (>90 %) by lactic acid bacteria and characterized by high similarity and low taxonomic diversity, whereas spoiled silage had highly diverse microbiomes with low abundances of lactic acid bacteria (<5 %) that were sometimes characterized by high levels of Enterobacteriaceae. Spatial position had a much stronger impact on the microbial community composition than feedstock type, sampling date, or production center location supporting previous studies demonstrating that ecology and not geography is a major driver of environmental microbiomes.

Bases genéticas y moleculares del cáncer colorrectal / Genetic and molecular basis in colorectal cancer

El cáncer colorrectal (CCR) es la tercera neoplasia más frecuente a un nivel mundial. El riesgo de CCR depende de factores genéticos y ambientales que interactúan en el proceso de carcinogénesis mediante mecanismos epigenéticos. Aunque sólo el 25 % de los CCR presenta agregación familiar, en todos los casos de CCR entre los que se incluyen los esporádicos se producen mutaciones genéticas que desencadenan tres tipos distintos de vías moleculares de carcinogénesis que influyen en un comportamiento tumoral diferente. El conocimiento de los genes y las vías moleculares implicados en el desarrollo del CCR tiene unas aplicaciones clínicas debido a que ayuda a definir el pronóstico, a elaborar un consejo genético en caso de síndromehereditario y a diseñar un plan terapéutico más específico de acuerdo a las características moleculares del tumor. Por otro lado, según la teoría de las células madre, una célula madre del epitelio colónico con una acumulación de aberraciones genéticas puede ser la célula origen del CCR. El diseño de nuevos fármacos dirigidos contra marcadores de las células madre del CCR pueden potenciar la respuesta de la quimioterapia convencional y disminuir las recurrencias locales y metástasis a distancia (AU)

Colorectal cancer is the third most common cancer wordlwide. Relative CRC risk is defined by genetic and environmental factors contributing to carcinogenesis by epigenetic mechanisms. Though only a 25 % CRC has been determined to have a familiar agregation with an important genetic component, all cases of CRC including sporadic ones present genetic aberrations that initiate three distinct molecular pathways of carcinogenesis implicating in different tumoral behaviours. Investigations about genes and molecular pathways implicated in the development of CRC have clinic aplications due to it could contribute to determine prognosis, elaborate a genetic conseling in case of familiar agregation and design therapeutic strategies according with molecular characteristics of tumor. On the other hand, A stem cell located in colonic epithelium with an acumulation of genetic mutations could be the cell that initiates the origin of CRC. The design of stem cell-targeted drugs could enhance reponsiveness to traditional therapeutic strategies and reduce local recurrence and metástasis (AU)

An analytical model for rotator cuff repairs.

BACKGROUND: Currently, natural and synthetic scaffolds are being explored as augmentation devices for rotator cuff repair. When used in this manner, these devices are believed to offer some degree of load sharing; however, no studies have quantified this effect. Furthermore, the manner in which loads on an augmented rotator cuff repair are distributed among the various components of the repair is not known, nor is the relative biomechanical importance of each component. The objectives of this study are to (1) develop quasi-static analytical models of simplified rotator cuff repairs, (2) validate the models, and (3) predict the degree of load sharing provided by an augmentation scaffold. METHODS: The individual components of the repair constructs were modeled as non-linear springs, and the model equations were formulated based on the physics of springs in series and parallel. The model was validated and used to predict the degree of load sharing provided by a scaffold. Parametric sensitivity analysis was used to identify which of the component(s)/parameter(s) most influenced the mechanical behavior of the augmented repair models. FINDINGS: The validated models predict that load will be distributed approximately 70-80% to the tendon repair and approximately 20-30% to the augmentation component. The sensitivity analysis suggests that the greatest improvements in the force carrying capacity of a tendon repair may be achieved by improving the properties of the bone-suture-tendon interface. Future studies will perform parametric simulation to illustrate the manner in which changes to the individual components of the repair, representing different surgical techniques and scaffold devices, may influence the biomechanics of the repair construct.

Easy extrusion of honeycomb-shaped monoliths using Moroccan natural clays and investigation of their dynamic adsorptive behavior towards VOCs.

In the present work, honeycomb-shaped monoliths were easily extruded using local natural clays without the need of chemical binders. This finding allows significant cost reduction, in terms of not only additives and solvents but also the energy consumption required for their elimination by thermal treatment. The extruded monoliths were subject to mechanical strength testing in addition to the study of their thermal behavior, structural and textural properties. Moreover, one of their potential uses as VOCs adsorbents was evaluated in comparison with conventional packed bed by investigating their dynamic adsorptive and desorption behavior towards a model VOC of o-xylene type.

Effect of alternate energy substrates on mammalian brain metabolism during ischemic events.

Regulation of brain metabolism and cerebral blood flow involves complex control systems with several interacting variables at both cellular and organ levels. Quantitative understanding of the spatially and temporally heterogeneous brain control mechanisms during internal and external stimuli requires the development and validation of a computational (mathematical) model of metabolic processes in brain. This paper describes a computational model of cellular metabolism in blood-perfused brain tissue, which considers the astrocyte-neuron lactate-shuttle (ANLS) hypothesis. The model structure consists of neurons, astrocytes, extra-cellular space, and a surrounding capillary network. Each cell is further compartmentalized into cytosol and mitochondria. Inter-compartment interaction is accounted in the form of passive and carrier-mediated transport. Our model was validated against experimental data reported by Crumrine and LaManna, who studied the effect of ischemia and its recovery on various intra-cellular tissue substrates under standard diet conditions. The effect of ketone bodies on brain metabolism was also examined under ischemic conditions following cardiac resuscitation through our model simulations. The influence of ketone bodies on lactate dynamics on mammalian brain following ischemia is studied incorporating experimental data.

[Spontaneous retroperitoneal hematoma. Report of one case]. / Hematoma retroperitoneal espontáneo. Caso clínico.

Spontaneous retroperitoneal hematoma is a rare condition. We report a 78 year-old man with progressive pain in his right thigh and hip lasting one week. The pain subsequently was associated with abdominal pain in the right lower quadrant. Physical examination revealed pain to deep palpation of the area, associated with a diffuse positive rebound pain. An abdominal and pelvis CT scan showed an extensive mesenteric hematoma. During surgery, a large retroperitoneal encapsulated hematoma, without evidence of active bleeding, was found and drained. Pathology confirmed the diagnosis and was negative for cancer.

Hematoma retroperitoneal espontáneo: Caso clínico / Spontaneous retroperitoneal hematoma: Report of one case

Spontaneous retroperitoneal hematoma is a rare condition. We report a 78 year-old man with progressive pain in his right thigh and hip lasting one week. The pain subsequently was associated with abdominal pain in the right lower quadrant. Physical examination revealed pain to deep palpation of the area, associated with a diffuse positive rebound pain. An abdominal and pelvis CT scan showed an extensive mesenteric hematoma. During surgery, a large retroperitoneal encapsulated hematoma, without evidence of active bleeding, was found and drained. Pathology confirmed the diagnosis and was negative for cancer.

[Thrombosed cavernous hemangioma of the anterior mediastinum. A report of one case]. / Hemangioma cavernoso trombosado de mediastino anterior. A propósito de un caso.

Mediastinum hemangioma is a rare benign tumor. We performed surgery and present the first reported case in Chile. The patient is a 24-year-old symptomatic woman, referred to our hospital from a rural health center. The patient had all routine preoperative studies, chest radiographs and computed tomography of the thorax. We performed a median sternotomy with a complete resection of the mass. During the 36-month follow-up, she was well, asymptomatic and without relapse evidence. A review of the most outstanding characteristics of this rare tumor is presented.

Reactivation of aged model Pd/Ce0.68Zr0.32O2 three-way catalyst by high temperature oxidising treatment.

A deactivated (aged under redox-cycled model TWC feed-stream) Pd/Ce(0.68)Zr(0.32)O(2) catalyst is remarkably reactivated when subjected to a high temperature oxidising treatment whereas this effect is only marginal for Pd/Al(2)O(3), which indicates the key role of such treatment in restoring the Pd-Ce(0.68)Zr(0.32)O(2) interactions leading to highly active catalysts.

Loss of hepatitis A virus (HAV) antibodies after peripheral stem cell transplantation (PSCT).

The majority of patients with hepatitis A have a benign course, but some may develop fulminant hepatitis and hematological complications. Peripheral stem cell transplantation (PSCT) is associated with loss of immunity. There are no data regarding loss of HAV antibodies (anti-HAV) after PSCT. We retrospectively evaluated the persistence of anti-HAV in a nonvaccinated population that underwent PSCT. Serum detection of anti-HAV was determined before and after PSCT using a qualitative commercially available enzyme immunoassay. From January 1997 to March 2001, 136 (68%) of 201 patients tested (+) for anti-HAV prior to PSCT. Subsequent investigation of anti-HAV was possible in 36 of these patients at a median of 12 months after PSCT. The median age of patients was 47 years old; they had diagnoses of hematological malignancies (33) and solid tumors (three), and underwent autologous (31) and allogenic (five) PSCT. A total of 31 (86%) of 36 patients remained anti-HAV (+) and five (14%) became (-) after PSCT. The variables age, sex, diagnosis, type of PSCT, time of testing, and number of CD34 cells infused were not predictors of loss of anti-HAV. In conclusion, 14% of 36 nonvaccinated anti-HAV (+) patients lost their antibodies at a median of 12 months after PSCT.

Molecular cloning and characterization of a rat homolog of CAP, the adenylyl cyclase-associated protein from Saccharomyces cerevisiae.

We have isolated a rat cDNA whose expression suppresses the physiological consequences of the chromosomal disruption of CAP, the gene encoding the adenylyl cyclase-associated protein of Saccharomyces cerevisiae. Yeast CAP is a bifunctional protein: the NH2 terminus is necessary and sufficient for cellular responsiveness to activated RAS proteins, while the COOH terminus is required for normal cellular morphology and growth control. The rat MCH1 cDNA encodes a protein of 474 amino acids that is 36% identical to S. cerevisiae CAP and is capable of suppressing the loss of the COOH-terminal functions of CAP when expressed in yeast. The MCH1 protein therefore appears to be a structural and functional homolog of the yeast cyclase-associated proteins. Northern analysis of MCH1 gene expression shows it to be constitutively expressed in all cell and tissue types examined. The cloning of a rat homolog of CAP, in addition to the cloning of a human CAP homolog by Matviw et al. (Matviw, H., Yu, G., and Young, D. (1992) Mol. Cell. Biol. 12, 5033-5040), demonstrates that both cyclase-associated proteins and their functions may have evolved with mammalian cells.

Etiologia de otitis media aguda purulenta en lactantes. / Etiology of acute suppurative otitis media in infants

Se estudiaran 41 lactantes con el diagnostico de otitis media aguda. Streptococcus pneumoniae fue el agente mas frecuente aislado (48,8%). Haemophilus influenzae se aislo como segunda etilogia. La parecentesis esta indicada en casos muy especificos y el pediatra general puede prescindir de ella en la mayoria de ellos. Conociendo las posibilidades etiologicas del cuadro se puede elegir una terapia adecuada