Contributions of Microdialysis to New Alternative Therapeutics for Hepatic Encephalopathy

Hepatic encephalopathy (HE) is a common complication of cirrhosis, of largely reversible impairment of brain function occurring in patients with acute or chronic liver failure or when the liver is bypassed by portosystemic shunts. The mechanisms causing this brain dysfunction are still largely unclear. The need to avoid complications caused by late diagnosis has attracted interest to understand the mechanisms underlying neuronal damage in order to find markers that will allow timely diagnosis and to propose new therapeutic alternatives to improve the care of patients. One of the experimental approaches to study HE is microdialysis; this technique allows evaluation of different chemical substances in several organs through the recollection of samples in specific places by semi-permeable membranes. In this review we will discuss the contributions of microdialysis in the understanding of the physiological alterations in human hepatic encephalopathy and experimental models and the studies to find novel alternative therapies for this disease.     

Safety models incorporating graph theory based transit indicators

There is a considerable need for tools to enable the evaluation of the safety of transit networks at the planning stage. One interesting approach for the planning of public transportation systems is the study of networks. Network techniques involve the analysis of systems by viewing them as a graph composed of a set of vertices (nodes) and edges (links). Once the transport system is visualized as a graph, various network properties can be evaluated based on the relationships between the network elements. Several indicators can be calculated including connectivity, coverage, directness and complexity, among others. The main objective of this study is to investigate the relationship between network-based transit indicators and safety. The study develops macro-level collision prediction models that explicitly incorporate transit physical and operational elements and transit network indicators as explanatory variables. Several macro-level (zonal) collision prediction models were developed using a generalized linear regression technique, assuming a negative binomial error structure. The models were grouped into four main themes: transit infrastructure, transit network topology, transit route design, and transit performance and operations. The safety models showed that collisions were significantly associated with transit network properties such as: connectivity, coverage, overlapping degree and the Local Index of Transit Availability. As well, the models showed a significant relationship between collisions and some transit physical and operational attributes such as the number of routes, frequency of routes, bus density, length of bus and 3+ priority lanes.     

A model of cadmium accumulation in the liver and kidney of sheep derived from soil and dietary characteristics

BACKGROUND: Cadmium accumulates in sheep tissues and often approaches the legal limit for human consumption in kidneys. Previous models have focused on transfer from plants to sheep but have restricted value due to seasonal and species variation in plant cadmium concentration. We created a model for the accumulation of cadmium in sheep using empirical relationships previously derived for accumulation in sheep kidney and liver from feeds, together with equations for accumulation in feeds derived from soil characteristics. The combined model relates soil cadmium to liver and kidney concentrations. RESULTS: Sensitivity analysis demonstrated that the kidney accumulated cadmium faster than the liver and the greatest influence was the total cadmium concentration in the soil. The weight gain of the sheep and soil pH where the feed was grown had relatively minor influences on cadmium concentration in liver or kidney. CONCLUSION: A combined model of soil, plant and sheep kidney and liver characteristics enables concentrations of cadmium in sheep liver and kidney to be predicted from soil characteristics. This will enable the long‐term risks of specific sites to be predicted with greater accuracy than if just plant cadmium concentrations were utilized. Copyright © 2010 Society of Chemical Industry     

Amination of Polymeric Braid Structures to Improve Tendon Healing: An Experimental Comparison

Several polymers are researched for tendon repair as polyethylene terephthalate (PET) and polylactic acid (PLA). These are biocompatible and useful in scaffolding repair though with minimal success due to long-term failure. There is a need to improve such scaffolds' design and physical–chemical nature. This work concerns surface functionalization of polymeric braids (PET and PLA) that fulfill the high mechanical demands of tissues such as tendons. The functionalization aims to incorporate amine groups in the braids' surface, improve cell adhesion, and consequently, the poor healing rate of these tissues and the biointegration of the braids. Two approaches are compared: the direct application of NH₃ plasma and the surface grafting of EDA after O₂ plasma activation. X-ray photoelectron spectroscopy (XPS) shows that amine groups are effectively introduced onto the samples' surfaces. Besides, the plasma parameters chosen do not compromise the topography and tensile behavior of the braids. Resazurin assay and scanning electron microscopy show that the NH₃ treatment improves cell–biomaterial interaction as improved cell adhesion and proliferation are observed. Both approaches are safe for biomedical applications. The NH₃ plasma approach is more environmentally friendly, faster, and easier to scale-up, showing potential for application in the final hybrid medical device.     

Poly(3-methylthiophene)/MnO2 composite electrodes as electrochemical capacitors

Composite electrodes prepared by electrodeposition of manganese oxide on titanium substrates modified with poly(3-methylthiophene) (PMeT) were investigated and compared with Ti/MnO₂ electrodes. The polymer films were prepared by galvanostatic deposition at 2 mA cm⁻² with different deposition charges (250 and 1500 mC cm⁻²). The electrodes were characterized by cyclic voltammetry in 1 mol L⁻¹ Na₂SO₄ and by scanning electron microscopy. The results show a very significant improvement in the specific capacitance of the oxide due the presence of the polymer coating. For Ti/MnO₂ the specific capacitance was of 122 F g⁻¹, while Ti/PMeT₂₅₀/MnO₂ and Ti/PMeT₁₅₀₀/MnO₂ displayed values of 218 and 66 F g⁻¹, respectively. If only oxide mass is considered, the capacitances of the composite electrode increases to 381 and 153 F g⁻¹, respectively. The micrographs of samples show that the polymer coating leads to very significant changes in the morphology of the oxide deposit, which in consequence, generate the improvement observed in the charge storage property.     

Lactobacilli isolated from kefir grains: evidence of the presence of S-layer proteins

In the present study we report for the first time the presence of S-layer proteins in Lactobacillus kefir and Lactobacillus parakefir isolated from kefir grains. Soluble whole-cell protein profile obtained either by mechanical disruption (X-press) or by a combined treatment with lysozyme and SDS on whole cells, showed a significant band of apparent molecular mass of 66-71 kDa as measured by SDS-PAGE. The intensity of this band was considerably reduced when cells were treated with 5 M-LiCl. The above mentioned proteins were recovered in the LiCl extracts. After dialysis and concentration, the proteins extracted were able to reassemble in a regular array. Negative staining of these protein preparations were analysed by transmission electron microscopy and a paracrystalline arrangement was seen. Thin sections of bacteria analysed by transmission electron micrographs showed an outermost layer over the bacterial cell wall, that was lost after the LiCl treatment. The production of this surface structure under different culture conditions was also evaluated. Finally, the relationship between the presence of S-layer proteins and surface properties (e.g. adhesion to Caco-2 cells, autoaggregation, and hemagglutination) was investigated.     

Antifungal activity of natural and enzymatically-modified flavonoids isolated from citrus species

The antifungal activity of isolated flavonoids from Citrus species, such as naringin, hesperidin and neohesperidin, and enzymatically-modified derivatives of these compounds, was studied on four fungi often found as food contaminants: Aspergillus parasiticus, Aspergillus flavus, Fusarium semitectum and Penicillium expansum. Although all the flavonoids showed antifungal activity, the intensity of this activity depended on the type of fungus and compound used. The hesperetin glucoside laurate strongly inhibited the mycelial growth of P. expansum, while prunin decanoate was the most inhibiting flavonoid for A. flavus, A. parasiticus, and F. semitectum.     

Morphological characterization of the growing front of Rhizopus oligosporus in solid media

Rhizopus oligosporus is used to prepare tempeh and is formed by hyphae which grow as a complex branched structure with irregular borders. The objective of this research was to characterize the macro and micro structural development of R. oligosporus colonies growing on solid media in Petri dishes through image processing and fractal dimension. Stereomicroscope images of the colony were used to detecting the zone in which the fractal dimension (FDE) of the edge (growing front) of the colony represented 97% of the maximum FDE for the 80% of the image of the border. Evaluated characteristics were: radial growth, number of tips in the growing front and the average length of hypha. Two simultaneous events of different and oscillating magnitude were detected in the growing front: branching and increase of the average hypha length. Biomass had a good correlation with radius of the colony, fractal dimension of texture (FDT) and number of tips in the border.     

Particulate matter air pollution disrupts endothelial cell barrier via calpain-mediated tight junction protein degradation

ABSTRACT: BACKGROUND: : Exposure to particulate matter (PM) is a significant risk factor for increased cardiopulmonary morbidity and mortality. The mechanism of PM-mediated pathophysiology remains unknown. However, PM is proinflammatory to the endothelium and increases vascular permeability in vitro and in vivo via ROS generation. OBJECTIVES: We explored the role of tight junction proteins as targets for PM-induced loss of lung endothelial cell (EC) barrier integrity and enhanced cardiopulmonary dysfunction. METHOD: S: Changes in human lung EC monolayer permeability were assessed by Transendothelial Electrical Resistance (TER) in response to PM challenge (collected from Ft. McHenry Tunnel, Baltimore, MD, particle size >0.1 um). Biochemical assessment of ROS generation and Ca2+ mobilization were also measured. RESULTS: : PM exposure induced tight junction protein ZO-1 relocation from the cell periphery, which was accompanied by significant reductions in ZO-1 protein levels but not in adherens junction proteins (VE-cadherin and beta-catenin). N-acetyl-cysteine (NAC, 5mM) reduced PM-induced ROS generation in ECs, which further prevented TER decreases and atteneuated ZO-1 degradation. PM also mediated intracellular calcium mobilization via the transient receptor potential cation channel M2 (TRPM2), in a ROS-dependent manner with subsequent activation of the Ca2+-dependent protease calpain. PM-activated calpain is responsible for ZO-1 degradation and EC barrier disruption. Overexpression of ZO-1 attenuated PM-induced endothelial barrier disruption and vascular hyperpermeability in vivo and in vitro. CONCLUSIONS: : These results demonstrate that PM induces marked increases in vascular permeability via ROS-mediated calcium leakage via activated TRPM2, and via ZO-1 degradation by activated calpain. These findings support a novel mechanism for PM-induced lung damage and adverse cardiovascular outcomes.