Mechanical properties and cytotoxicity of 3Y-TZP bioceramics reinforced with Al(2)O(3) particles

The influence of Al(2)O(3) addition and sintering parameters on the mechanical properties and cytotoxicity of tetragonal ZrO(2)-3 mol% Y(2)O(3) ceramics was evaluated. Samples containing 0, 10, 20 and 30 wt.% of Al(2)O(3) particles were prepared by cold uniaxial pressing (80 MPa) and sintered in air at 1500, 1550 and 1600 degrees C for 120 min. The effects of the sintering conditions on the microstructure were analyzed by X-ray diffraction analysis and scanning electron microscopy. Hardness and fracture toughness were determined by the Vickers indentation method and the mechanical resistance by four-point bending tests. As a preliminary biological evaluation, ""in vitro"" cytotoxicity tests were realized to determine the cytotoxic level of the ZrO(2)-Al(2)O(3) composites, using the neutral red uptake method with NCTC clones L929 from the American Type Culture Collection (ATCC) bank. Fully dense ceramic materials were obtained with a hardness ranging between 1340 HV and 1585 HV, depending on the amount of Al(2)O(3) in the ZrO(2) matrix. On the other hand, no significant influence of the Al(2)O(3) addition on fracture toughness was observed, exhibiting values near 8 MPa m(1/2) for all compositions and sintering conditions studied. The non-cytotoxic behavior, the elevated fracture toughness, the good bending strength (sigma(f) = 690 MPa) and the elevated Weibull`s modulus (m = 11) exhibited by the material, show that these ceramic composites are highly suitable biomaterials for dental implant applications. (C) 2008 Elsevier Ltd and Techna Group S.r.l. All rights reserved.

Dynamic Imaging in Electrical Impedance Tomography of the Human Chest With Online Transition Matrix Identification

One of the electrical impedance tomography objectives is to estimate the electrical resistivity distribution in a domain based only on electrical potential measurements at its boundary generated by an imposed electrical current distribution into the boundary. One of the methods used in dynamic estimation is the Kalman filter. In biomedical applications, the random walk model is frequently used as evolution model and, under this conditions, poor tracking ability of the extended Kalman filter (EKF) is achieved. An analytically developed evolution model is not feasible at this moment. The paper investigates the identification of the evolution model in parallel to the EKF and updating the evolution model with certain periodicity. The evolution model transition matrix is identified using the history of the estimated resistivity distribution obtained by a sensitivity matrix based algorithm and a Newton-Raphson algorithm. To numerically identify the linear evolution model, the Ibrahim time-domain method is used. The investigation is performed by numerical simulations of a domain with time-varying resistivity and by experimental data collected from the boundary of a human chest during normal breathing. The obtained dynamic resistivity values lie within the expected values for the tissues of a human chest. The EKF results suggest that the tracking ability is significantly improved with this approach.

Precipitation of Laves phase in a 28%Cr-4%Ni-2%Mo-Nb superferritic stainless steel

The main objective of the present work was to study the precipitation of the Laves phase in the X1 CrNiMoNb 28 4 2 (Werkstoff-Nr. DIN 1.4575) superferritic stainless steel employing several complementary techniques of microstructural analysis. The phase that precipitated in largest quantity in the DIN 1.4575 steel was the sigma (sigma) phase. However, along grain boundaries, after aging at 850 degrees C, a Laves phase of the MgZn2 type, with a hexagonal C14 crystal structure and chemical composition (Fe,Cr,Ni)(2)(Nb,Mo,Si), was also identified. Growth of the Laves phase is curtailed by exhaustion of niobium of the matrix and by the presence of the sigma phase, which also precipitates in the vicinity of the grain boundaries, however in larger amounts. No chi (chi) or austenite phases were detected in the temperature range studied. (C) 2007 Elsevier Inc. All rights reserved.

Age-related association of rDNA and telomeres with the nuclear matrix in mouse hepatocytes

Transcribed sequences have been suggested to be associated with the nuclear matrix, differing from non-transcribing sequences, which have been reported to be contained in DNA loops. However, although a dozen of genes have their expression level affected by aging, data on chromatin-nuclear matrix interactions under this physiological condition are still scarce. In the present study, liver imprints from young, adult and old mice were subjected to FISH (fluorescence in situ hybridization) for 45S rDNA and telomeric sequences, with or without a lysis treatment to produce extended chromatin fibres. There was an increased amount of 45S rDNA sequences located in DNA loops as the animals grow older, while telomeric sequences were always observed in DNA loops irrespective of the animal age. We assume that active rRNA genes associate with the nuclear matrix, while DNA loops contain silent sequences. Transcription of each 45S rDNA repeat unit is suggested to be dependent on its interaction with the nuclear matrix.

Standardization and determination of photostability of leaf extracts of Pothomorphe umbellata L. Miq (pariparoba) and evaluation of the inhibition in vitro of metalloproteinases 2 and 9 in skin

Most researches that have been done until today about the beneficial effects of hariparoha (Pothomorphe umbellata L. Miq) have been done with root extract of this species, but the use in large scale would compromise the sustainable exploration of this natutral resource. In this sense, the utilization of pariparoha leaves, substituting the roots, in the cosmetic industry does not put in risk the existence of the species. In this work the concentration of 4-nerolidyl-cathecol (4-NC) in leaf extract was determined by the analytical methodology validated in our laboratory. The concentration of 4-NC in leaf extract was around 30% less than that of root extract, obtained in the same way. Concerning the study of the photostability of a leaves extract solution containing 4-NC did not demonstrate meaningful alterations in the spectrometry, profile after 2 hours of exposure under UVB radiation, showing its stability under this conditions. Metalloproteinases (MMPs) cure endopeptidases that are zinc-dependent, involved in remodeling extracellular matrix (ECM), that are important in the appearance of typical photoaging wrinkles. In this work the capacity of leaf extract of P. umbellata to inhibit MMP-2 and 9 activities of hairless mouse skin in vitro by zymography gel was also evalutated. The leaf extract (0,1 mg/mL) inhibit in 80% activity of this enzymes, according to the densitometric zymography evaluation.

Impedimetric immunosensor for electronegative low density lipoprotein (LDL(-)) based on monoclonal antibody adsorbed on (polyvinyl formal)-gold nanoparticles matrix

Monoclonal antibodies (MAb) have been commonly applied to measure LDL in vivo and to characterize modifications of the lipids and apoprotein of the LDL particles. The electronegative low density lipoprotein (LDL(-)) has an apolipoprotein B-100 modified at oxidized events in vivo. In this work, a novel LDL-electrochemical biosensor was developed by adsorption of anti-LDL(-) MAb on an (polyvinyl formal)-gold nanoparticles (PVF-AuNPs)-modified gold electrode. Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) were used to characterize the recognition of LDL-. The interaction between MAb-LDL(-) leads to a blockage in the electron transfer of the [Fe(CN)(6)](4-)/K(4)[Fe(CN)(6)](3-) redox couple, which may could result in high change in the electron transfer resistance (R(CT)) and decrease in the amperometric responses in CV analysis. The compact antibody-antigen complex introduces the insulating layer on the assembled surface, which increases the diameter of the semicircle, resulting in a high R(CT), and the charge transferring rate constant k(0) decreases from 18.2 x 10(-6) m/s to 4.6 x 10(-6) m/s. Our results suggest that the interaction between MAb and lipoprotein can be quantitatively assessed by the modified electrode. The PVF-AuNPs-MAb system exhibited a sensitive response to LDL(-), which could be used as a biosensor to quantify plasmatic levels of LDL(-). (C) 2011 Elsevier B.V. All rights reserved.

Influence of gamma radiation onto polymeric matrix with papain

Papain is a proteolytic enzyme that has been widely used as debridement agent for scars and wound healing treatment. However, papain presents low stability, which limits its use to extemporaneous or short shelf-life formulations. The purpose of this study was to entrap papain into a polymeric matrix in order to obtain a drug delivery system that could be used as medical device. Since these systems must be sterile, gamma radiation is an interesting option and presents advantages in relation to conventional agents: no radioactive residues are formed: the product can be sterilized inside the final packaging and has an excellent reliability. The normative reference for the establishment of the sterilizing dose determines 25 kGy as the inactivation dose for viable microorganisms. A silicone dispersion was selected to prepare membranes containing 2% (w/w) papain. Irradiated and non-irradiated membranes were simultaneously assessed in order to verify whether gamma radiation interferes with the drug-releasing profile. Results showed that irradiation does not affect significantly papain release and its activity. Therefore papain shows radioresistance in the irradiation conditions applied. In conclusion, gamma radiation can be easily used as sterilizing agent without affecting the papain release profile and its activity onto the biocompatible device is studied. (C) 2009 Elsevier Ltd. All rights reserved.

Development and In Vitro Evaluation of Propranolol Hydrochloride Controlled Release Tablets Using HPMC as Matrix Former

The purpose of this paper was to produce controlled-release matrices with 120 mg of propranolol hydrochloride (PHCl) employing hydroxypropyl methylcellulose (HPMC, Methocel (R) K100) as the gel forming barrier. Although this class of polymers has been commonly used for direct compression, with the intent of use reduced polymer concentrations to achieve controlled drug release, in this study tablets were produced by the wet granulation process. HPMC percentages ranged from 15-34 % and both soluble and non soluble diluents were tested in the 10 proposed tablet compositions. Dissolution testing of matrices was performed over a 12 h period in 1.2 pH medium (the first 2 h) and in pH 6.8 (10 h). Dissolution kinetic analysis was performed by applying Zero-order, First-order and Higuchi models with the aim of elucidating the drug release mechanism. All physical-chemical characteristics such as average weight, friability, hardness, diameter, height, and drug content were in accordance to the pharmacopeial specifications. Taking into account that PHCl is a very soluble drug, low concentrations (15 %) of HPMC were sufficient to reduce the drug release and to promote controlled release of PHCl, presenting good dissolution efficiencies, between 50 % and 63 %. The Higuchi model has presented the best fit to the 15 % HPMC formulations, indicating that the main release mechanism was diffusion. It could be concluded that the application of the wet granulation method reduced matrices erosion and promoted controlled release of the drug at low HPMC percentages.

On the mechanisms of phenothiazine-induced mitochondrial permeability transition: Thiol oxidation, strict Ca(2+) dependence, and cyt c release

Phenothiazines (PTZ) are drugs widely used in the treatment of schizophrenia. Trifluoperazine, a piperazinic PTZ derivative, has been described as inhibitor of the mitochondrial permeability transition (MPT). We reported previously the antioxidant activity of thioridazine at relatively low concentrations associated to the inhibition of the MPT (Brit. J. Pharmacol., 2002;136:136-142). In this study, it was investigated the induction of MPT by PTZ derivatives at concentrations higher than 10 mu M focusing on the molecular mechanism involved. PTZ promoted a dose-response mitochondrial swelling accompanied by mitochondrial transmembrane potential dissipation and calcium release, being thioridazine the most potent derivative. PTZ-induced MPT was partially inhibited by CsA or Mg(2+) and completely abolished by the abstraction of calcium. The oxidation of reduced thiol group of mitochondrial membrane proteins by PTZ was upstream the VIP opening and it was not sufficient to promote the opening of PTP that only occurred when calcium was present in the mitochondrial matrix. EPR experiments using DMPO as spin trapping excluded the participation of reactive oxygen species on the PTZ-induced MPT. Since 117 give rise to cation radicals chemically by the action of peroxidases and cyanide inhibited the PTZ-induced swelling, we propose that VIZ bury in the inner mitochondrial membrane and the chemically generated 117 cation radicals modify specific thiol groups that in the presence of Ca(2+) result in MPT associated to cytochrome c release. These findings contribute for the understanding of mechanisms of MET induction and may have implications for the cell death induced by PTZ. (C) 2010 Elsevier Inc. All rights reserved.

Impact of adenosine nucleotide translocase (ANT) proline isomerization on Ca(2+)-induced cysteine relative mobility/mitochondrial permeability transition pore

Mitochondrial membrane carriers containing proline and cysteine, such as adenine nucleotide translocase (ANT), are potential targets of cyclophilin D (CyP-D) and potential Ca(2+)-induced permeability transition pore (PTP) components or regulators; CyP-D, a mitochondrial peptidyl-prolyl cis-trans isomerase, is the probable target of the PTP inhibitor cyclosporine A (CsA). In the present study, the impact of proline isomerization (from trans to cis) on the mitochondrial membrane carriers containing proline and cysteine was addressed using ANT as model. For this purpose, two different approaches were used: (i) Molecular dynamic (MD) analysis of ANT-Cys(56) relative mobility and (ii) light scattering techniques employing rat liver isolated mitochondria to assess both Ca(2+)-induced ANT conformational change and mitochondrial swelling. ANT-Pro(61) isomerization increased ANT-Cys(56) relative mobility and, moreover, desensitized ANT to the prevention of this effect by ADP. In addition, Ca(2+) induced ANT ""c"" conformation and opened PTP; while the first effect was fully inhibited, the second was only attenuated by CsA or ADP. Atractyloside (ATR), in turn, stabilized Ca(2+)-induced ANT ""c"" conformation, rendering the ANT conformational change and PTP opening less sensitive to the inhibition by CsA or ADP. These results suggest that Ca(2+) induces the ANT ""c"" conformation, apparently associated with PTP opening, but requires the CyP-D peptidyl-prolyl cis-trans isomerase activity for sustaining both effects.

BthMP: a new weakly hemorrhagic metalloproteinase from Bothrops moojeni snake venom

In this work, a new weakly hemorrhagic metalloproteinase (BthMP) was purified from Bothrops moojeni snake venom. This enzyme was homogeneous by native and SDS-PAGE. It showed a polypeptide chain of 23.5 kDa, pI=7.1, and N-terminal blocked. BthMP is comprised of high proteolytic activity on casein, fibrin and bovine fibrinogen, with no coagulating, esterase or phospholipase A(2) activities; it was inhibited by EDTA, EGTA and 1,10-phenanthroline and maintained its activity on pH from 7.0 to 9.0 and temperature from 5-40 degrees C. Assays with metal ions showed that Ca(2+) is an activator, whereas Zn(2+) and Hg(2+) inhibited about 50 and 80% of its activity, respectively. The edema evidenced the important role of the toxin in the inflammatory activity of the venom. BthMP also caused unclotting, and provoked histological alterations in the gastrocnemius muscle of mice inducing hemorrhage, necrosis and leukocytic infiltrate. The molecular mass and the inhibition assays suggest that the metal loproteinase BthMP belongs to class P-I of SVMPs. (c) 2008 Elsevier Ltd. All rights reserved.

Isolation and structural characterization of a new fibrin(ogen)olytic metalloproteinase from Bothrops moojeni snake venom

A proteinase, named BmooMP alpha-I, from the venom of Bothrops moojeni, was purified by DEAE-Sephacel, Sephadex G-75 and heparin-agarose column chromatography. The enzyme was purified to homogeneity as judged by its migration profile in SDS-PAGE stained with coomassie blue, and showed a molecular mass of about 24.5 kDa. Its complete cDNA was obtained by RT-PCR and the 615 bp codified for a mature protein of 205 amino acid residues. The multiple alignment of its deduced amino acid sequence and those of other snake venom metalloproteinases showed a high structural similarly, mainly among class P-IB proteases. The enzyme cleaves the A alpha-chain of fibrinogen first, followed by the B beta-chain, and shows no effects on the gamma-chain. On fibrin, the enzyme hydrolyzed only the beta-chain, leaving the gamma-dimer apparently untouched. It was devoid of phospholipase A(2), hemorrhagic and thrombin-like activities. Like many venom enzymes, it is stable at pH values between 4 and 10 and stable at 70 degrees C for 15 min. The inhibitory effects of EDTA on the fibrinogenolytic activity suggest that BmooMP alpha-I is a metalloproteinase and inhibition by beta-mercaptoethanol revealed the important role of the disulfide bonds in the stabilization of the native structure. Aprotinin and benzamidine, specific serine proteinase inhibitors, had no effect on BmooMP alpha-I activity. Since the BmooMP alpha-I enzyme was found to cause defibrinogenation when administered i.p. on mice, it is expected that it may be of medical interest as a therapeutic agent in the treatment and prevention of arterial thrombosis. (C) 2007 Elsevier Ltd. All rights reserved.

The game to play: expanding the co-opetition proposal through the strategic games matrix

Purpose - Using Brandenburger and Nalebuff`s 1995 co-opetition model as a reference, the purpose of this paper is to seek to develop a tool that, based on the tenets of classical game theory, would enable scholars and managers to identify which games may be played in response to the different conflict of interest situations faced by companies in their business environments. Design/methodology/approach - The literature on game theory and business strategy are reviewed and a conceptual model, the strategic games matrix (SGM), is developed. Two novel games are described and modeled. Findings - The co-opetition model is not sufficient to realistically represent most of the conflict of interest situations faced by companies. It seeks to address this problem through development of the SGM, which expands upon Brandenburger and Nalebuff`s model by providing a broader perspective, through incorporation of an additional dimension (power ratio between players) and three novel, respectively, (rival, individualistic, and associative). Practical implications - This proposed model, based on the concepts of game theory, should be used to train decision- and policy-makers to better understand, interpret and formulate conflict management strategies. Originality/value - A practical and original tool to use game models in conflict of interest situations is generated. Basic classical games, such as Nash, Stackelberg, Pareto, and Minimax, are mapped on the SGM to suggest in which situations they Could be useful. Two innovative games are described to fit four different types of conflict situations that so far have no corresponding game in the literature. A test application of the SGM to a classic Intel Corporation strategic management case, in the complex personal computer industry, shows that the proposed method is able to describe, to interpret, to analyze, and to prescribe optimal competitive and/or cooperative strategies for each conflict of interest situation.

Development of novel bioanodes for ethanol biofuel cell using PAMAM dendrimers as matrix for enzyme immobilization

This paper describes the preparation and application of a novel bioanode for use in ethanol/O(2) biofuel cells based upon immobilization of alcohol dehydrogenase (ADH) and polyamidoamine (PAMAM) dendrimers onto carbon cloth platforms. The power density measurements indicated a direct relationship between the amount of anchored ADH and the anode power values, which increased upon enzyme loading. The power density values ranged from 0.04 to 0.28 mW cm(-2), and the highest power density was achieved with the bioanode prepared with 28 U of ADH, which provided a power density of 0.28 mW cm(-2) at 0.3 V. The latter power output values were the maximum observed, even for higher enzyme concentrations. Stability of the bioanodes was quite satisfactory, since there was no appreciable reduction of enzymatic activity during the measurements. The method of bioanode preparation described here has proven to be very effective. The PAMAM dendrimer represents a friendly environment for the immobilization of enzymes, and it is stable and capable of generating high power density compared to other immobilization methods. (C) 2010 Elsevier B.V. All rights reserved.

Spectroelectrochemical Properties and Lithium Ion Storage in Self-Assembled Nanocomposites from TiO(2)

Layer-by-layer (LbL) nanocomposite films from TiO(2) nanoparticles and tungsten-based oxides (WO(x)H(y)), as well as dip-coating films of TiO(2) nano particles, were prepared and investigated by electrochemical techniques under visible light beams, aiming to evaluate the lithium ion storage and chromogenic properties. Atomic force microscopy (AFM) images were obtained for morphological characterization of the Surface of the materials, which have similar roughness. Cyclic voltammetry and chronoamperometry measurements indicated high storage capacity of lithium ions in the LbL nanocomposite compared with the dip-coating film, which was attributed to the faster lithium ion diffusion rate within the self-assembled matrix. On the basis of the data obtained from galvanostatic intermittent titration technique (GITT), the values of lithium ion diffusion coefficient (D(Li)) for TiO(2)/WO(x)H(y) were larger compared with those for TiO(2). The rate of the coloration front in the matrices was investigated using a spectroelectrochemical method based oil GITT, allowing the determination of the ""optical"" diffusion coefficient (D(op)) as a function of the amount of lithium ions previously inserted into the matrices. The Values of D(Li) and D(op) suggested the existence of phases with distinct contribution to lithium ion diffusion rates and electrochromic efficiency. Moreover, these results aided a better understanding of the temporal change of current density and absorbance during the ionic electro-insertion, which is important for the possible application of these materials in lithium ion batteries and electrohromic devices.