Increased oxygen radical and high-dietary-carbohydrate pancreatic damage.

These data suggest that an improved understanding of the relationship between high dietary carbohydrate and the rate of lipid peroxidation may give some insight into possible treatment modalities for pancreatic damages and may shed light on molecular mechanisms underlying certain pathological processes. High dietary carbohydrate lesions are age related and induced alterations on ceruloplasmin, phospholipids, total proteins, copper and zinc serum levels. Significantly increased serum and pancreatic amylase, and lipoperoxide determinations were observed in 20 month old rats. Cu-Zn superoxide dismutase was decreased in these animals. Daily injection of Cu-Zn superoxide dismutase conjugated with polyethylene glycol (SOD-PEG) prevented the serum and pancreatic changes, indicating that superoxide radical is an important intermediate to high dietary carbohydrate lesion.

Ebselen and cytokine-induced nitric oxide synthase expression in insulin-producing cells

Interleukin-1 (IL-1) may be a mediator of β-cell damage in insulin-dependent diabetes mellitus (IDDM). The IL-1 mechanism of action on insulin-producing cells probably includes activation of the transcription nuclear factor κB (NF-κB), increased transcription of the inducible form of nitric oxide synthase (iNOS) and the subsequent production of nitric oxide (NO). Reactive oxygen intermediates, particularly H2O2, have been proposed as second messengers for NF-κB activation. In the present study, we tested whether ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), a glutathione peroxidase mimicking compound, could counteract the effects of IL-1β, H2O2 and alloxan in rat pancreatic islets and in the rat insulinoma cell line RINm5F (RIN cells). Some of these experiments were also reproduced in human pancreatic islets. Ebselen (20 μM) prevented the increase in nitrite production by rat islets exposed to IL-1β for 6 hr and induced significant protection against the acute inhibitory effects of alloxan or H2O2 exposure, as judged by the preserved glucose oxidation rates. However, ebselen failed to prevent the increase in nitrite production and the decrease in glucose oxidation and insulin release by rat islets exposed to IL-1β for 24 hr. Ebselen prevented the increase in nitrite production by human islets exposed for 14 hr to a combination of cytokines (IL-1β, tumor necrosis factor-α and interferon-γ). In RIN cells, ebselen counteracted both the expression of iNOS mRNA and the increase in nitrite production induced by 6 hr exposure to IL-β but failed to block IL-1β-induced iNOS expression following 24 hr exposure to the cytokine. Moreover, ebselen did not prevent IL-1β-induced NF-κB activation. As a whole, these data indicate that ebselen partially counteracts cytokine-induced NOS activation in pancreatic β-cells, an effect not associated with inhibition of NF-κB activation.

A lung computed tomographic assessment of positive end-expiratory pressure-induced lung overdistension

The aim of this study was to assess positive end-expiratory pressure (PEEP)-induced lung overdistension and alveolar recruitment in six patients with acute lung injury (ALI) using a computed tomographic (CT) scan method. Lung overdistension was first determined in six healthy volunteers in whom CT sections were obtained at FRC and at TLC with a positive airway pressure of 30 cm H2O. In patients, lung volumes were quantified by the analysis of the frequency distribution of CT numbers on the entire lung at zero end-expiratory pressure (ZEEP) and PEEP. In healthy volunteers at FRC, the distribution of the density histograms was monophasic with a peak at -791 ± 12 Hounsfield units (HU). The lowest CT number observed was -912 HU. At TLC, lung volume increased by 79 ± 35% and the peak CT number decreased to -886 ± 26 HU. More than 70% of the increase in lung volume was located below -900 HU, suggesting that this value can be considered as the threshold separating normal aeration from overdistension. In patients with ALI, at ZEEP the distribution of density histograms was either monophasic (n = 3) or biphasic (n = 3). The mean CT number was -319 ± 34 HU. At PEEP 13 ± 3 cm H2O, lung volume increased by 47 ± 19% whereas mean CT number decreased to -538 ± 171 HU. PEEP induced a mean alveolar recruitment of 320 ± 160 ml and a mean lung overdistension of 238 ± 320 ml. In conclusion, overdistended lung parenchyma of healthy volunteers is characterized by a CT number below -900 HU. This threshold can be used in patients with ALI for differentiating PEEP-induced alveolar recruitment from lung overdistension.

Electromyographic fatigue threshold of the biceps brachii muscle during dynamic contraction

The purpose of this study was to identify the Electromyographic Fatigue Threshold (EMG FT) of the biceps brachii muscle bilaterally during the elbow flexion in tests performed in different times: 30 second test, 1 minute test and fatiguing test, in concentric (CC) and eccentric (EC) phases. Nine healthy young men performed the elbow flexion with loads corresponding at 25%, 35% and 45% of the one repetition maximum (1-RM) in separate days. The results indicated that the test applied for the biceps brachii muscle during elbow flexion induced a progressive increment of EMG activity with time indicating muscle fatigue and allowed the identification of the EMG FT. The three tests presented no difference of EMG FT between CC and EC phases bilaterally.

Antimicrobial endodontic compounds do not modulate alkylation-induced genotoxicity and oxidative stress in vitro

Objective: To investigate if formocresol, paramonochlorophenol, or calcium hydroxide modulate the genotoxic effects induced by the oxidatively damaging agent hydrogen peroxide (H 2O 2) or the alkylating agent methyl methanesulfonate (MMS) in vitro by using single cell gel (comet) assay. Study design: Chinese hamster ovary (CHO) cells in culture were exposed directly to formocresol, paramonochlorophenol, or calcium hydroxide (adjusted to 100 μg/mL) for 1 hour at 37°C. Subsequently the cultures were incubated with increasing concentrations (0-10 μmol/L) of MMS in phosphate-buffered solution (PBS) for 15 minutes at 37°C or of H 2O 2 at increasing concentrations (0-100 μmol/L) in distilled water for 5 minutes on ice. The negative control cells were treated with PBS for 1 hour at 37°C. The parameter from the comet assay (tail moment) was assessed by the Kruskal-Wallis nonparametric test followed by a post hoc analysis (Dunn test). Results: Clear concentration-related effects were observed for the genotoxin-exposed CHO cells. Increase of MMS-induced DNA damage was not significantly altered by the presence of the compounds tested. Similarly, no significant changes were observed when hydrogen peroxide was used with the endodontic compounds evaluated. Conclusion: Formocresol, paramonochlorophenol, and calcium hydroxide are not able to modulate alkylation-induced genotoxicity or oxidative DNA damage as depicted by the single cell gel (comet) assay. © 2006 Mosby, Inc. All rights reserved.

Assessment of DNA damage by extracts and fractions of Strychnos pseudoquina, a Brazilian medicinal plant with antiulcerogenic activity

Strychnos pseudoquina St. Hil. is a native plant of the Brazilian Savannah, used in popular medicine to treat a number of conditions. Since it contains large quantities of alkaloids with proven antiulcer activity, we tested the genotoxic potential of crude extracts and fractions containing alkaloids and flavonoids from the leaves of this plant, on Salmonella typhimurium and performed the micronucleus test on peripheral blood cells of mice treated in vivo. The results showed that the methanol extract of the leaves of S. pseudoquina is mutagenic to the TA98 (-S9) and TA100 (+S9, -S9) strains of Salmonella. The dichloromethane extract was not mutagenic to any of the tested strains. Fractions enriched with alkaloids or flavonoids were not mutagenic. In vivo tests were done on the crude methanol extract in albino Swiss mice, which were treated, by gavage, with three different doses of the extract. The highest dose tested (1800 mg/kg b.w.) induced micronuclei after acute treatment, confirming the mutagenic potential of the methanol extract of the leaves of S. pseudoquina. In high doses, constituents of S. pseudoquina compounds act on DNA, causing breaks and giving rise to micronuclei in the blood cells of treated animals. © 2006 Elsevier Ltd. All rights reserved.

Damage detection in a benchmark structure using AR-ARX models and statistical pattern recognition

Structural health monitoring (SHM) is related to the ability of monitoring the state and deciding the level of damage or deterioration within aerospace, civil and mechanical systems. In this sense, this paper deals with the application of a two-step auto-regressive and auto-regressive with exogenous inputs (AR-ARX) model for linear prediction of damage diagnosis in structural systems. This damage detection algorithm is based on the. monitoring of residual error as damage-sensitive indexes, obtained through vibration response measurements. In complex structures there are. many positions under observation and a large amount of data to be handed, making difficult the visualization of the signals. This paper also investigates data compression by using principal component analysis. In order to establish a threshold value, a fuzzy c-means clustering is taken to quantify the damage-sensitive index in an unsupervised learning mode. Tests are made in a benchmark problem, as proposed by IASC-ASCE with different damage patterns. The diagnosis that was obtained showed high correlation with the actual integrity state of the structure. Copyright © 2007 by ABCM.

DNA damage and nitric oxide synthesis in experimentally infected Balb/c mice with Trypanosoma cruzi

This study aimed to evaluate whether experimental Chagas disease in acute phase under benznidazole therapy can cause DNA damage in peripheral blood, liver, heart, and spleen cells or induce nitric oxide synthesis in spleen cells. Twenty Balb/c mice were distributed into four groups: control (non-infected animals); Trypanosoma cruzi infected; T. cruzi infected and submitted to benznidazole therapy; and only treated with benznidazole. The results obtained with the single cell gel (comet) assay showed that T. cruzi was able induce DNA damage in heart cells of both benznidazole treated or untreated infected mice. Similarly, T. cruzi infected animals showed an increase of DNA lesions in spleen cells. Regarding nitric oxide synthesis, statistically significant differences (p < 0.05) were observed in all experimental groups compared to negative control, the strongest effect observed in the T. cruzi infected group. Taken together, these results indicate that T. cruzi may increase the level of DNA damage in mice heart and spleen cells. Probably, nitric oxide plays an important role in DNA damaging whereas benznidazole was able to minimize induced T. cruzi genotoxic effects in spleen cells. © 2006 Elsevier Inc. All rights reserved.

Anthracycline-induced cardiotoxicity

The anthracyclines constitute a group of drugs widely used for the treatment of a variety of human tumors. However, the development of irreversible cardiotoxicity has limited their use. Anthracycline-induced cardiotoxicity can persist for years with no clinical symptoms. However, its prognosis becomes poor after the development of overt heart failure, possibly even worse than ischemic or idiopathic dilated cardiomyopathies. Due to the successful action of anthracyclines as chemotherapic agents, several strategies have been tried to prevent/ attenuate their side effects. Although anthracycline-induced injury appears to be multifactorial, a common denominator among most of the proposed mechanisms is cellular damage mediated by reactive oxygen species. However, it remains controversial as to whether antioxidants can prevent such side effects given that different mechanisms may be involved in acute versus chronic toxicity. The present review applies a multisided approach to the critical evaluation of various hypotheses proposed over the last decade on the role of oxidative stress in cardiotoxicity induced by doxorubicin, the most used anthracycline agent. The clinical diagnosis and treatment is also discussed. © 2008 Bentham Science Publishers Ltd.

Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility status

Background: Amifostine is an efficient cytoprotector against toxicity caused by some chemotherapeutic drugs. Doxorubicin, a potent anticancer anthracycline, is known to produce spermatogenic damage even in low doses. Although some studies have suggested that amifostine does not confer protection to doxorubicin-induced testicular damage, schedules and age of treatment have different approach depending on the protocol. Thus, we proposed to investigate the potential cytoprotective action of amifostine against the damage provoked by doxorubicin to prepubertal rat testes (30-day-old) by assessing some macro and microscopic morphometric parameters 15, 30 and 60 days after the treatment; for fertility evaluation, quantitative analyses of sperm parameters and reproductive competence in the adult phase were also carried out.Methods: Thirty-day-old male rats were distributed into four groups: Doxorubicin (5 mg/kg), Amifostine (400 mg/kg), Amifostine/Doxorubicin (amifostine 15 minutes before doxorubicin) and Sham Control (0.9% saline solution). Standard One Way Anova parametric and Anova on Ranks non-parametric tests were applied according to the behavior of the obtained data; significant differences were considered when p < 0.05.Results: The rats killed 30 and 60 days after doxorubicin treatment showed diminution of seminiferous epithelium height and reduction on the frequency of tubular sections containing at least one type of differentiated spermatogonia; reduction of sperm concentration and motility and an increase of sperm anomalous forms where observed in doxorubicin-treated animals. All these parameters were improved in the Amifostine/Doxorubicin group only when compared to Doxorubicin group. Such reduction, however, still remained below the values obtained from the Sham Control group. Nevertheless, the reproductive competence of doxorubicin-treated rats was not improved by amifostine pre-administration.Conclusions: These results suggest that amifostine promotes a significant reduction of the doxorubicin long-term side effects on the seminiferous epithelium of prepubertal rats, which is reflected in the epidydimal fluid parameters in the adult phase. However, fertility status results suggest that such protection may not be effective against sperm DNA content damage. Further investigation of sperm DNA integrity must be carried out using amifostine and doxorubicin-treated experimental models. © 2010 Vendramini et al; licensee BioMed Central Ltd.

Effects of 12-week overground walking training at ventilatory threshold velocity in type 2 diabetic women

This study analyzed the effects of overground walking training at ventilatory threshold (VT) velocity on glycaemic control, body composition, physical fitness and lipid profile in DM2 women. Nineteen sedentary patients were randomly assigned to a control group (CG; n=10, 55.9±2.2 years) or a trained group (TG; n=9, 53.4±2.3 years). Both groups were subjected to anthropometric measures, a 12-h fasting blood sampling and a graded treadmill exercise test at baseline and after a 12-week period, during which TG followed a training program involving overground walking at VT velocity for 20-60min/session three times/week. Significant group×time interactions (P<0.05) in glycated hemoglobin (HbA1c), body mass, body mass index (BMI), peak oxygen uptake (VO 2peak) and exercise duration were observed as effects of training exercise, whereas intervention did not induced significant changes (P>0.05) in fasting blood glucose, submaximal fitness parameters and lipid profile. Our results suggest that overground walking training at VT velocity improves long term glycaemic control, body composition and exercise capacity, attesting for the relevance of this parameter as an effective strategy for the exercise intensity prescription in DM2 population. © 2011 Elsevier B.V.

Baccharis dracunculifolia, the main source of green propolis, exhibits potent antioxidant activity and prevents oxidative mitochondrial damage

Baccharis dracunculifolia DC (Asteraceae) is the main botanical source used by honeybees to produce Brazilian green propolis whose hepatoprotective properties have been already described. In this work we investigated the protective effects of the glycolic extract of B. dracunculifolia (GEBd) against oxidative stress in isolated rat liver mitochondria (RLM). The GEBd was prepared by fractionated percolation using propylene glycol as solvent. The total phenols and flavonoids, which are substances with recognized antioxidant action, were quantified in GEBd and the phytochemical analysis was carried out by HPLC. GEBd exhibited significant scavenger activity towards DPPH radicals and superoxide anions in a concentration-dependent manner, and also a Fe 2+ chelating activity. GEBd decreased the basal H 2O 2 generation and the Fe 2+- or t-BuOOH-induced ROS production in isolated mitochondria. Lipid oxidation of mitochondrial membranes, protein thiol groups and GSH oxidation were also prevented by GEBd. This shows that B. dracunculifolia exhibit potent antioxidant activity protecting liver mitochondria against oxidative damage and such action probably contribute to the antioxidant and hepatoprotective effects of green propolis. © 2011 Elsevier Ltd.

Field-induced length changes in the spin-liquid candidate κ-(BEDT-TTF) 2Cu 2(CN) 3

Measurements of the coefficient of thermal expansion on the spin-liquid candidate κ-(BEDT-TTF) 2Cu 2(CN) 3 have revealed distinct and strongly anisotropic lattice effects around 6 K - a possible spin liquid instability. In order to study the effects of a magnetic field on the low-temperature spin-liquid state, dilatometric measurements have been conducted both as a function of temperature at B = const. and as a function of field at T = const. While the 6 K anomaly is found to be insensitive to magnetic fields B ≤ 10 T, the maximum field applied, surprisingly strong B -induced effects are observed for magnetic fields applied along the in-plane b-axis. Above a threshold field of 0.5 T < B c ≤ 1 T, a jump-like anomaly is observed in the b-axis lattice parameter. This anomaly, which is located at 8.7 K at B = 1 T, grows in size and shifts to lower temperatures with increasing the magnetic field. Although the anomaly bears resemblance to a first-order phase transition, the lack of hysteresis suggests otherwise. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemoprotective activity of the isoflavones, genistein and daidzein on mutagenicity induced by direct and indirect mutagens in cultured HTC cells

Isoflavones are phenolic compounds widely distributed in plants and found in a high percentage in soybeans. They have important biological properties and are regarded as potential chemopreventive agents. The aim of this study was to verify the preventive effect of two soy isoflavones (genistein and daidzein) by a micronucleus assay, analysis of GST activity, and real-time RT-PCR analysis of GSTa2 gene expression. Mutagens of direct (doxorubicin) and indirect (2-aminoanthracene) DNA damage were used. Hepatoma cells (HTC) were treated with genistein or daidzein for 26 h at noncytotoxic concentrations; 10 μM when alone, and 0.1, 1.0 and 10 μM when combined with genotoxic agents. The micronucleus test demonstrated that both isoflavones alone had no genotoxic effect. Genistein showed antimutagenic effects at 10 μM with both direct and indirect DNA damage agents. On phase II enzyme regulation, the current study indicated an increase in total cytoplasmic GST activity in response to genistein and daidzein at 10 μM supplementation. However, the mRNA levels of GSTa2 isozymes were not differentially modulated by genistein or daidzein. The results point to an in vitro antimutagenic activity of genistein against direct and indirect DNA damage-induced mutagenicity. © 2012 Springer Science+Business Media B.V.

The natural absence of RPA1N domain did not impair Leishmania amazonensis RPA-1 participation in DNA damage response and telomere protection.

We have previously shown that the subunit 1 of Leishmania amazonensis RPA (LaRPA-1) alone binds the G-rich telomeric strand and is structurally different from other RPA-1. It is analogous to telomere end-binding proteins described in model eukaryotes whose homologues were not identified in the protozoan's genome. Here we show that LaRPA-1 is involved with damage response and telomere protection although it lacks the RPA1N domain involved with the binding with multiple checkpoint proteins. We induced DNA double-strand breaks (DSBs) in Leishmania using phleomycin. Damage was confirmed by TUNEL-positive nuclei and triggered a G1/S cell cycle arrest that was accompanied by nuclear accumulation of LaRPA-1 and RAD51 in the S phase of hydroxyurea-synchronized parasites. DSBs also increased the levels of RAD51 in non-synchronized parasites and of LaRPA-1 and RAD51 in the S phase of synchronized cells. More LaRPA-1 appeared immunoprecipitating telomeres in vivo and associated in a complex containing RAD51, although this interaction needs more investigation. RAD51 apparently co-localized with few telomeric clusters but it did not immunoprecipitate telomeric DNA. These findings suggest that LaRPA-1 and RAD51 work together in response to DNA DSBs and at telomeres, upon damage, LaRPA-1 works probably to prevent loss of single-stranded DNA and to assume a capping function.