Effect of surface treatment on fatigue behavior of metal/carbon fiber laminates

The tension-tension fatigue behavior of metal/fiber laminates (MFLs) has been investigated. These MFLs were produced with carbon fiber and by treating the aluminum foil to promote adhesion bonding by two methods: sulfuric-boric-oxalic acid anodization (SBOA) and chromic acid anodization (CAA). The surface treatments were evaluated by scanning electron microscopy (SEM) techniques and roughness measurements. It was observed that MFL specimens produced with SBOA treatments presents comparable mechanical results when compared with MFLs produced with CAA treatment. Microstructural observations of the fracture surfaces by SEM show hackle formation is the predominant damage mechanism.

The slippery slope - Critical perspectives on in vitro research methodologies

Objectives. This paper attempts to provide critical perspectives on common in vitro research methodologies, including shear bond testing, wear testing, and load-to-failure tests. Origins of interest in high-quality laboratory data is reviewed, in vitro data is categorized into property and simulation protocols, and two approaches are suggested for establishing clinical validity. It is hoped that these insights will encourage further progress toward development of in vitro tests that are validated against clinical performance and/or by producing clinically validated failure or damage mechanisms.Materials and methods. Published shear and tensile bond data (macro and micro) is examined in light of published finite element analyses (FEA). This data is subjected to a Weibull scaling analysis to ascertain whether scaling is consistent with failure from the bonded interface or not. Wear tests results are presented in light of the damage mechanism(s) operating. Quantitative wear data is re-examined as being dependent upon contact pressure. Load-to-failure test results are re-analyzed by calculating contact stresses at failure for 119 tests from 54 publications over more than 25 years.Results. FEA analyses and reported failure modes (adhesive, mixed, cohesive) are consistent with failure not involving interfacial "shear stresses" as calculated in published work. Weibull scaling clearly suggests failure involving external surfaces of specimens, not interfacial origins. Contact stresses (pressures) are clearly an important variable in wear testing and are not well-controlled in published work. Load-to-failure tests create damage not seen clinically due to excessively high contact stresses. Most contact stresses in the 119 tests examined were calculated to be between 1000 MPa and 5000 MPa, whereas clinical contact stresses at wear facets have been measured not to exceed 40 MPa.Conclusions. Our community can do a much better job of designing in vitro tests that more closely simulate clinical conditions, especially when contact is involved. Journals are encouraged to thoughtfully consider a ban on publishing papers using bond tests and load-to-failure methods that are seriously flawed and have no clinical relevance. (C) 2011 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

A SequenceSpace analysis of Lys49 phospholipases A2: Clues towards identification of residues involved in a novel mechanism of membrane damage and in myotoxicity

'SequenceSpace' analysis is a novel approach which has been used to identify unique amino acids within a subfamily of phospholipases A2 (PLA2) in which the highly conserved active site residue Asp49 is substituted by Lys (Lys49-PLA2s). Although Lys49-PLA2s do not bind the catalytic co-factor Ca2+ and possess extremely low catalytic activity, they demonstrate a Ca2+-independent membrane damaging activity through a poorly understood mechanism, which does not involve lipid hydrolysis. Additionally, Lys49-PLA2s possess combined myotoxic, oedema forming and cardiotoxic pharmacological activities, however the structural basis of these varied functions is largely unknown. Using the 'SequenceSpace' analysis we have identified nine residues highly unique to the Lys49-PLA2 sub-family, which are grouped in three amino acid clusters in the active site, hydrophobic substrate binding channel and homodimer interface regions. These three highly specific residue clusters may have relevance for the Ca2+-independent membrane damaging activity. Of a further 15 less stringently conserved residues, nine are located in two additional clusters which are well isolated from the active site region. The less strictly conserved clusters have been used in predictive sequence searches to correlate amino acid patterns in other venom PLA2s with their pharmacological activities, and motifs for presynaptic and combined toxicities are proposed.

DNA damage in peripheral blood mononuclear cells of patients undergoing anti-tuberculosis treatment

Tuberculosis (TB), a chronic infectious disease, is a major cause of morbidity and mortality worldwide. Expression of iNOS and consequent production of NO during the inflammatory process is an important defense mechanism against TB bacteria. We have tested whether pulmonary TB patients undergoing anti-tuberculosis treatment present DNA damage, and whether this damage is related to oxidative stress, by evaluating total hydrophilic antioxidant capacity and iNOS expression. DNA damage in peripheral blood mononuclear cells from patients and healthy tuberculin test (PPD) positive controls was evaluated by single-cell gel electrophoresis (comet assay), and iNOS expression was measured by qPCR. We also evaluated total hydrophilic antioxidant capacity in plasma from patients and controls. Compared to controls, pulmonary TB patients under treatment presented increased DNA damage, which diminished during treatment. Also, the antioxidant capacity of these individuals was increased at the start of treatment, and reduced during treatment. TB patients showed lower iNOS expression, but expression tended to increase during treatment. Our results indicate that pulmonary TB patients under anti-TB treatment exhibit elevated DNA damage in peripheral blood mononuclear cells. This damage was not related to nitric oxide but may be due to other free radicals. (C) 2012 Elsevier B.V. All rights reserved.

Antioxidant activity of indigo and its preventive effect against ethanol-induced DNA damage in rat gastric mucosa

Ethanol-induced oxidative damage is commonly associated with the generation of reactive oxygen molecules, leading to oxidative stress. Considering that antioxidant activity is an important mechanism of action involved in cytoprotection, the aim of this work was to evaluate the antioxidant properties of the alkaloid indigo (1) (2 mg/kg, p. o.), obtained from the leaves of Indigofera truxillensis Kunth (Fabaceae), on rat gastric mucosa submitted to ethanol-induced (100%, 1 mL, p.o.) gastric ulcer. Enzymatic assays and DNA fragmentation analysis were performed. When ethanol was administered to the control group, the sulfhydryl content (SH) and the glutathione peroxidase (GPx) activity decreased by 41% and 50%, respectively; in contrast, superoxide dismutase (SOD) and glutathione reductase (GR) activities increased by 56% and 67%, respectively. Additionally, myeloperoxidase (MPO) activity, a marker for free radical generation caused by polymorphonuclear neutrophil (PMN) tissue infiltration, also increased 4.5-fold after ethanol treatment. Rat gastric mucosa exposed to ethanol showed DNA fragmentation. Indigo alkaloid pretreatment protected rats from ethanol-induced gastric lesions. This effect was determined by the ulcerative lesion area (ULA), indicating an inhibition of around 80% at 2 mg/kg. This alkaloid also diminished GPx activity, which was higher than that observed with ethanol alone. However, this effect was counterbalanced by increased GR activity. Indigo was unable to restore alterations in SOD activity promoted by ethanol. After indigo pretreatment, SH levels and MPO activity remained normal and gastric mucosa DNA damage caused by ethanol was also partially prevented by indigo. These results suggest that the gastroprotective mechanisms of indigo include non-enzymatic antioxidant effects and the inhibition of PMN infiltration which, in combination, partially protect the gastric mucosa against ethanol-induced DNA damage.

Anti-clastogenic effect of beta-glucan extracted from barley towards chemically induced DNA damage in rodent cells

beta-Glucan (BG) was tested in vitro to determine its potential clastogenic and/or anti-clastogenic activity, and attempts were made to elucidate its possible mechanism of action by using combinations with an inhibitor of DNA polymerase. The study was carried out on cells deficient (CHO-k1) and cells proficient (HTC) in phases I and II enzymes, and the DNA damage was assessed by the chromosomal aberration assay. BG did not show a clastogenic effect, but was anti-clastogenic in both cell lines used, and at all concentrations tested (2.5, 5 and 10 mg/mL) in combination with damage inducing agents (methylmethane sulfonate in cell line CHO-k1, and methylmethane sulfonate or 2-aminoanthracene in cell line HTC). BG also showed a protective effect in the presence of a DNA polymerase beta inhibitor (cytosine arabinoside-3-phosphate, Ara-C), demonstrating that BG does not act through an anti-mutagenic mechanism of action involving DNA polymerase beta.

Protective effect of beta-glucan extracted from Saccharomyces cerevisiae, against DNA damage and cytotoxicity in wild-type (k1) and repair-deficient (xrs5) CHO cells

A large number of functional foods, including those that contain P-glucan, have been shown to prevent the development of cancer and other chronic diseases. The aim of the present study was to elucidate its mechanism of action, as well as to understand its effects as an antigenotoxic, anticlastogenic agent, and to determine its capacity to preserve cell viability. The investigation was carried out in the CHO-k1 and CHO-xrs5 cell lines. The cytokinesis-blocked micronucleus assay indicated that the different doses of beta-glucan examined (5, 10, 20 and 40 mu g/ml) did not show clastogenic effects. In the CHO-k1 cell line, a chemopreventive effect could be observed in all the protocols tested: pre-treatment (% reduction of 35.0-57.3), simultaneous treatment (simple - 5 reduction of 19.7-55.6 and with pre-incubation - of 42.7-56.4) and post-treatment (% reduction of 17.9-37.6). This finding indicates mechanisms of action involving desmutagenesis and bio-antimutagenesis, albeit the latter having a lesser role. However, in the repair-deficient CHO-xrs5 cells, beta-glucan did not show a protective effect with post-treatment (% reduction of 2.96), thus supporting the involvement of bioantimutagenesis. The comet assay in CHO-k1 cells demonstrated that beta-glucan has neither a genotoxic nor an antigenotoxic effect. Cell viability tests indicated that beta-glucan preserves cell viability in both cell lines, preventing apoptotic events. These findings suggest that beta-glucan, when present in foods, could provide them with nutraceutical characteristics and act as a dietary supplement, or that P-glucan could be used in new drug development. (c) 2006 Elsevier Ltd. All rights reserved.

Brown Recluse Spider Venom: Proteomic Analysis and Proposal of a Putative Mechanism of Action

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Protective effects of beta-glucan extracted from barley against benzo[a]pyrene-induced DNA damage in hepatic cell HepG2

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Annexin 1 peptides protect against experimental myocardial ischemia-reperfusion: analysis of their mechanism of action

Myocardial reperfusion injury is associated with the infiltration of blood-borne polymorphonuclear leukocytes. We have previous described the protection afforded by annexin 1 (ANXA1) in an experimental model of rat myocardial ischemia-reperfusion (IR) injury. We examined the 1) amino acid region of ANXA1 that retained the protective effect in a model of rat heart IR; 2) changes in endogenous ANXA1 in relation to the IR induced damage and after pharmacological modulation; and 3) potential involvement of the formyl peptide receptor (FPR) in the protective action displayed by ANXA1 peptides. Administration of peptide Ac2-26 at 0, 30, and 60 min postreperfusion produced a significant protection against IR injury, and this was associated with reduced myeloperoxidase activity and IL-1 beta levels in the infarcted heart. Western blotting and electron microscopy analyses showed that IR heart had increased ANXA1 expression in the injured tissue, associated mainly with the infiltrated leukocytes. Finally, an antagonist to the FPR receptor selectively inhibited the protective action of peptide ANXA1 and its derived peptides against IR injury. Altogether, these data provide further insight into the protective effect of ANXA1 and its mimetics and a rationale for a clinical use for drugs developed from this line of research.

Mechanism of micronuclei formation in polyploidizated cells of Allium cepa exposed to trifluralin herbicide

The trifluralin is an agent that promotes a cellular damage due to its direct action on the microtubules. This action leads to a decontrol in the cellular division, bringing about polyploid cells. In this work, we show the evidences that the exceeding genetical material of theses polyploidizated cells tends to be eliminated from the nucleus in the form of micronucleus. Our analyses prove this fact, both by the presence of a number of cells carrying micronucleus, and by the evidences of the elimination of the exceeding material itself, after exposition of the Allium cepa root tips tested with several concentration of trifluralin herbicide. It was noticed that the residual concentration induced a number of polyploid cells, micronuclei and mini cells. Inferences about the implications of the elimination of genetic material from micronuclei, such as cell viability and apoptosis, are also presented. (c) 2007 Elsevier B.V. All rights reserved.

Calcium-Independent Membrane Damage by Venom Phospholipases A(2)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Toxic mechanism of nickel exposure on cardiac tissue

The incidence of cardiovascular disease has increased in the general population, and cardiac damage is indicated as one important cause of mortality. In addition, pollution and metal exposure have increased in recent years. For this reason, toxic effects of metals, such as nickel, and their relation to cardiac damage should be urgently established. Although free radical-mediated cellular damage and reactive oxygen species have been theorized as contributing to the nickel mechanism of toxicity, recent investigations have established that free radicals may be important contributors to cardiac dysfunction. However, there is little information on the effect of nickel exposure on markers of oxidative stress in cardiac tissue. Nickel exposure (Ni2+ 100 mg L-1 from NiSO4) significantly increased lipoperoxide and total lipid concentrations in cardiac tissue. We also observed increased serum levels of cholesterol (59%), lactate dehydrogenase (LDH-64%), and alanine transaminase (ALT-30%) in study animals. The biochemical parameters recovered to the control values with tocopherol intake (0.2 mg 200 g-1). Vitamin E alone significantly decreased the lipoperoxide concentration and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the heart. Since no alterations were observed in catalase and GSH-Px activities by nickel exposure while SOD activities were decreased, we conclude that superoxide radical (O2 -) generated by nickel exposure is of primary importance in the pathogenesis of cardiac damage. Tocopherol, by its antioxidant activity, decreased the toxic effects of nickel exposure on heart of rats.

Toxic mechanism of cadmium exposure on cardiac tissue

The presence of toxic substances in the workplace environment requires systematic evaluation of exposure and health status in exposed subjects. Cadmium is a highly toxic element found in water. Although free mediated cellular damage and reactive oxygen species (ROS), had been theorized as contributing to the cadmium mechanism of toxicity, and recent investigations have established that free radicals may be important contributors to cardiac dysfunction, there is little information on the effect of cadmium exposure on markers of oxidative stress in cardiac tissue. Cadmium exposure (Cd2+ - 100 mg/1-from CdCl2) in drinking water, during 15 days, significantly increased lipoperoxide and decreased the activities of superoxide dismutase and glutathione peroxidase. No alterations were observed in catalase activity in heart of rats with cadmium exposure. We also observed decreased glycogen and glucose concentration and increased total lipid content in cardiac tissue of rats with cadmium exposure. The decreased activities of alanine transaminase and aspartate transaminase reflected decreased metabolic protein degradation, and increased lactate dehydrogenase activity was related with increases in capacity of glycolysis. Since the metabolic pathways were altered by cadmium exposure, we can conclude that Cd2+ exposure induced ROS and initiate some series of events that occur in the heart and resulted in metabolic pathways alterations.

Advanced ceramics: Evaluation of the mechanism of stock removal and ground surface quality

The aim of this work is to evaluate the mechanism of stock removal and the ground surface quality of advanced ceramics machined by a surface grinding process using diamond grinding wheels. The analysis of the grinding performance was done regarding the cutting surface wear behavior of the grinding wheel for ceramic workpieces. The ground surface was evaluated using Scanning Electron Microscopy (SEM). As a result it can be said that the mechanism of material removal in the grinding of ceramic is largely one of brittle fracture. The increase of the hmax can reduce the tangential force required by the process. Although, it results in an increase in the surface damage, reducing the mechanical properties of the ground component.