Evaluation of the genotoxic and anti-genotoxic activities of Silybin in human hepatoma cells (HepG2)

Silybin (SB), a constituent of the medicinal plant Silybum marianum, is reported to be a potent hepatoprotective agent, but little is currently known regarding its genotoxicity, mutagenicity and potential chemopreventive properties. In this study, we evaluated the ability of SB to induce DNA migration and micronuclei (MN) formation in human hepatoma cells (HepG2). Also, possible preventive effects of SB on MN formation induced by three different mutagens, bleomycin (BLEO), benzo[a] pyrene (B[alpha] P) and aflatoxin B(1) (AFB(1)), were studied. To clarify the possible mechanism of SB antimutagenicity, three treatment protocols were applied: pretreatment, in which SB was added before the application of the mutagens; simultaneous treatment, in which SB was added during treatment and post-treatment, in which SB was added after the application of the mutagens. At concentrations up to 100 mu M, SB was non-genotoxic, while at a concentration of 200 mu M, SB induced DNA migration, generated oxidized DNA bases, reduced cell viability, decreased the replicative index of the cells and induced oxidative stress. It is noteworthy that SB was able to reduce the genotoxic effect induced by B[alpha] P, BLEO and AFB1 in pretreatment and simultaneous treatments but had no significant effect on DNA damage induction in post-treatment. Taken together, our findings indicate that SB presents anti-genotoxic activity in vitro, which suggests potential use as a chemopreventive agent.

Systemic Model for Diagnosis of the Micro, Small and Medium Enterprises from Two Cities from the Countryside of the State of So Paulo in Brazil

This article presents a proposal of a systemic model composed for the micro and small companies (MSE) of the region of Ribeiro Preto and the agents which influenced their environment. The proposed model was based on Stafford Beer`s (Diagnosing the system for organizations. Chichester, Wiley, 1985) systemic methodologies VSM (Viable System Model) and on Werner Ulrich`s (1983) CSH (Critical Systems Heuristics). The VSM is a model for the diagnosis of the structure of an organization and of its flows of information through the application of the cybernetics concepts (Narvarte, In El Modelo del Sistema Viable-MSV: experiencias de su aplicacin en Chile. Proyecto Cerebro Colectivo del IAS, Santiago, 2001). On the other hand, CSH focus on the context of the social group applied to the systemic vision as a counterpoint to the organizational management view considered by the VSM. MSE of Ribeiro Preto and Sertozinho had been analyzed as organizations inserted in systems that relate and integrate with other systems concerning the public administration, entities of representation and promotion agencies. The research questions: which are the bonds of interaction among the subsystems in this process and who are the agents involved? The systemic approach not only diagnosed a social group, formed by MSE of Ribeiro Preto and Sertozinho, public authorities and support entities, but could also delineate answers that aimed the clarification of obscure questions generating financial assistance to the formularization of efficient actions for the development of this system.

EEG-based Brain-Computer Interfaces: An Overview of Basic Concepts and Clinical Applications in Neurorehabilitation

Some patients are no longer able to communicate effectively or even interact with the outside world in ways that most of us take for granted. In the most severe cases, tetraplegic or post-stroke patients are literally `locked in` their bodies, unable to exert any motor control after, for example, a spinal cord injury or a brainstem stroke, requiring alternative methods of communication and control. But we suggest that, in the near future, their brains may offer them a way out. Non-invasive electroencephalogram (EEG)-based brain-computer interfaces (BCD can be characterized by the technique used to measure brain activity and by the way that different brain signals are translated into commands that control an effector (e.g., controlling a computer cursor for word processing and accessing the internet). This review focuses on the basic concepts of EEG-based BC!, the main advances in communication, motor control restoration and the down-regulation of cortical activity, and the mirror neuron system (MNS) in the context of BCI. The latter appears to be relevant for clinical applications in the coming years, particularly for severely limited patients. Hypothetically, MNS could provide a robust way to map neural activity to behavior, representing the high-level information about goals and intentions of these patients. Non-invasive EEG-based BCIs allow brain-derived communication in patients with amyotrophic lateral sclerosis and motor control restoration in patients after spinal cord injury and stroke. Epilepsy and attention deficit and hyperactive disorder patients were able to down-regulate their cortical activity. Given the rapid progression of EEG-based BCI research over the last few years and the swift ascent of computer processing speeds and signal analysis techniques, we suggest that emerging ideas (e.g., MNS in the context of BC!) related to clinical neuro-rehabilitation of severely limited patients will generate viable clinical applications in the near future.

Development of an animal model for allergic conjunctivitis: influence of genetic factors and allergen concentration on immune response

Purpose: Animal models of diseases are extremely important in the study of the physiopathogenesis of human diseases and for testing novel therapeutic interventions. The present study aimed to develop an animal model that simulates human allergic conjunctivitis and to study how allergic response may be influenced by the allergen dose used for immunization and by genetic factors. Methods: Sixty C57Bl/6 mice and 60 BALB/c mice were immunized with placebo, or 5 mu g or 500 mu g of allergen derived from Dermatophagoides pteronyssinus. After ocular challenge, the mice were examined in order to clinically verify the occurrence or not of conjunctivitis. Material obtained from animals was used for total and specific IgE and IgG1 dosage, for assays of Der p-specific lymphocyte proliferation and supernatant cytokine dosage, and for histopathological evaluation of conjunctiva. Results: We developed a murine model of allergic conjunctivitis induced by D. pteronyssinus. The model is similar to human disease both clinically and according to laboratory findings. In mouse, conjunctivitis was associated with a Th2 cytokine profile. However, IL-10 appeared to be involved with disease blockade. Mice of different strains have distinct immune responses, depending on the sensitization dose. Conclusions: The murine model developed is suitable for the study of immunopathogenesis and as a template for future therapies. Using BALB/c and C57BL/6 mice, we demonstrated that genetic factors play a role in determining susceptibility and resistance, as well as in establishing the allergen concentration needed to induce or to block disease development.

Early and Late Results of Topical Diltiazem and Bethanechol for Chronic Anal Fissure: A Comparative Study

Background/Aims: Late efficacy of medical treatment of chronic anal fissure remains controversial due to high recurrence. This study aimed at analyzing safety and efficacy of topical diltiazem and bethanechol regarding healing and symptoms relief, safety, recurrence, and need for surgery. Methodology: This was a single-center non-randomized trial. Outcomes of 30 patients with chronic anal fissure treated with 2% diltiazem were compared to 30 patients treated with 0.1% bethanechol, both for eight weeks. Patients were assessed after seven days and eight weeks. Results: In diltiazem group, after seven days, 31% were symptomatic; after bethanechol, 71% (p=0.06). After seven days, fissure healing occurred in 19% after diltiazem and in 11% after bethanechol. After eight weeks, in both groups, 64% were asymptomatic; after diltiazem, 53% healed; after bethanechol, 50% (p=0.80). Success was the same for both groups: 63.3%. Groups were similar regarding complications. After diltiazem, 9 (30%) patients were operated on; and 11 (36.7%) after bethanechol (p=0.60). Recurrence occurred in 4 (13.3%) patients in both groups. Median time to recurrence after diltiazem was 15 (10-24) months and 7.5 (2-15) after bethanechol - p=0.15. Conclusions: Both treatments are safe and effective. Diltiazem may be associated to earlier relief and more sustained response.

Test-retest reliability of isokinetic strength and endurance tests in patients with intermittent claudication

The objective was to determine the reliability of isokinetic strength and endurance testing in the ankle joints of patients with intermittent claudication. Twenty-three patients with peripheral artery disease (PAD) and symptoms of intermittent claudication participated in the study. Isokinetic strength and endurance testing of the ankle joint were performed in symptomatic and asymptomatic legs on 3 separate days. Intraclass coefficient correlation of peak torque (PT) and total work (TW) ranged from 0.77 to 0.92 and 0.89 to 0.96, respectively. PT and TW increased significantly and similarly in both legs from day 1 to day 2 (PT: +42 +/- 84% in the symptomatic leg and +33 +/- 51% in the asymptomatic leg, p < 0.05;TW: +38 +/- 26% in the symptomatic leg and +26 +/- 50% in the asymptomatic leg, p < 0.05). In conclusion, isokinetic strength and endurance testing in the ankle joints of patients with PAD presents reliability coefficients ranging from 0.77 to 0.96. However, strength and endurance increased between the first and the other test sessions performed on separate days, suggesting that two test sessions are necessary for the accurate evaluation of strength and endurance in patients with PAD.

Impact of pressure profile and duration of recruitment maneuvers on morphofunctional and biochemical variables in experimental lung injury

Objective: To investigate the effects of the rate of airway pressure increase and duration of recruitment maneuvers on lung function and activation of inflammation, fibrogenesis, and apoptosis in experimental acute lung injury. Design: Prospective, randomized, controlled experimental study. Setting: University research laboratory. Subjects: Thirty-five Wistar rats submitted to acute lung injury induced by cecal ligation and puncture. Interventions: After 48 hrs, animals were randomly distributed into five groups (seven animals each): 1) nonrecruited (NR); 2) recruitment maneuvers (RMs) with continuous positive airway pressure (CPAP) for 15 secs (CPAP15); 3) RMs with CPAP for 30 secs (CPAP30); 4) RMs with stepwise increase in airway pressure (STEP) to targeted maximum within 15 secs (STEP15); and 5) RMs with STEP within 30 secs (STEP30). To perform STEP RMs, the ventilator was switched to a CPAP mode and positive end-expiratory pressure level was increased stepwise. At each step, airway pressure was held constant. RMs were targeted to 30 cm H(2)O. Animals were then ventilated for 1 hr with tidal volume of 6 mL/kg and positive end-expiratory pressure of 5 cm H(2)O. Measurements and Main Results: Blood gases, lung mechanics, histology (light and electronic microscopy), interleukin-6, caspase 3, and type 3 procollagen mRNA expressions in lung tissue. All RMs improved oxygenation and lung static elastance and reduced alveolar collapse compared to NR. STEP30 resulted in optimal performance, with: 1) improved lung static elastance vs. NR, CPAP15, and STEP15; 2) reduced alveolar-capillary membrane detachment and type 2 epithelial and endothelial cell injury scores vs. CPAP15 (p < .05); and 3) reduced gene expression of interleukin-6, type 3 procollagen, and caspase 3 in lung tissue vs. other RMs. Conclusions: Longer-duration RMs with slower airway pressure increase efficiently improved lung function, while minimizing the biological impact on lungs. (Crit Care Med 2011; 39:1074-1081)

The Essential Oil of Eucalyptus tereticornis and its Constituents, alpha- and beta-Pinene, Show Accelerative Properties on Rat Gastrointestinal Transit

The essential oil of Eucalyptus tereticornis (EOET) has pharmacological activities but their effects on the gastrointestinal tract are yet unknown. It possesses alpha- and beta-pinene as minor constituents, isomers largely used as food or drink additives. In this work, we studied their actions on gut motility. After feeding with a liquid test meal, conscious rats received perorally EOET, alpha-, or beta-pinene, and the fractional dye retention was determined. EOET and its constituents decreased the gastric retention. In anesthetized rats, pinenes increased gastric tonus, while enhancing the meal progression in the small intestine of conscious rats. Both alpha- and beta-pinene contracted gastric strips in vitro but relaxed the duodenum. Conversely, EOET relaxed both the gastric and duodenal strips. In conclusion, EOET accelerates the gastric emptying of liquid, and part of its action is attributed to the contrasting effects induced by alpha- and beta-pinene on the gut.

Validation of the National Institutes of Health Stroke Scale, Modified Rankin Scale and Barthel Index in Brazil: The Role of Cultural Adaptation and Structured Interviewing

Background: We aimed to validate three widely used scales in stroke research in a multiethnic Brazilian population. Methods: The National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Barthel Index (BI) were translated, culturally adapted and applied by two independent investigators. The mRS was applied with or without a previously validated structured interview. Interobserver agreement (kappa statistics) and intraclass correlation coefficients were calculated. Results: 84 patients underwent mRS (56 with and 28 without a structured interview), 57 BI and 62 NIHSS scoring. Intraclass correlation coefficient was 0.902 for NIHSS and 0.967 for BI. For BI, interobserver agreement was good (kappa = 0.70). For mRS, the structured interview improved interobserver agreement (kappa = 0.34 without a structured interview; 0.75 with a structured interview). Conclusion: The NIHSS, BI and mRS show good validity when translated and culturally adapted. Using a structured interview for the mRS improves interobserver concordance rates. Copyright (C) 2008 S. Karger AG, Basel

Rabies virus in insectivorous bats: Implications of the diversity of the nucleoprotein and glycoprotein genes for molecular epidemiology

Insectivorous bats are the main reservoirs of rabies virus (RABV) in various regions of the world. The aims of this study were to (a) establish genealogies for RABV strains from different species of Brazilian insectivorous bats based on the nucleoprotein (N) and glycoprotein (G) genes, (b) investigate specific RABV lineages associated with certain genera of bats and (c) identify molecular markers that can distinguish between these lineages. The genealogic analysis of N and G from 57 RABV strains revealed seven genus-specific clusters related to the insectivorous bats Myotis, Eptesicus, Nyctinomops, Molossus, Tadarida, Histiotus and Lasiurus. Molecular markers in the amino acid sequences were identified which were specific to the seven clusters. These results, which constitute a novel finding for this pathogen, show that there are at least seven independent epidemiological rabies cycles maintained by seven genera of insectivorous bats in Brazil. (C) 2010 Elsevier Inc. All rights reserved.

Downward longwave radiation estimates for clear and all-sky conditions in the Sertozinho region of So Paulo, Brazil

The accurate estimate of the surface longwave fluxes contribution is important for the calculation of the surface radiation budget, which in turn controls all the components of the surface energy budget, such as evaporation and the sensible heat fluxes. This study evaluates the performance of the various downward longwave radiation parameterizations for clear and all-sky days applied to the Sertozinho region in So Paulo, Brazil. Equations have been adjusted to the observations of longwave radiation. The adjusted equations were evaluated for every hour throughout the day and the results showed good fits for most of the day, except near dawn and sunset, followed by nighttime. The seasonal variation was studied by comparing the dry period against the rainy period in the dataset. The least square linear regressions resulted in coefficients equal to the coefficients found for the complete period, both in the dry period and in the rainy period. It is expected that the best fit equation to the observed data for this site be used to produce estimates in other regions of the State of So Paulo, where such information is not available.

Agribusiness Opportunity Costs and Environmental Legal Protection: Investigating Trade-Off on Hotspot Preservation in the State of So Paulo, Brazil

Prior to deforestation, So Paulo State had 79,000 km(2) covered by Cerrado (Brazilian savanna) physiognomies, but today less than 8.5% of this biodiversity hotspot remains, mostly in private lands. The global demand for agricultural goods has imposed strong pressure on natural areas, and the economic decisions of agribusiness managers are crucial to the fate of Cerrado domain remaining areas (CDRA) in Brazil. Our aim was to investigate the effectiveness of Brazilian private protected areas policy, and to propose a feasible alternative to promote CDRA protection. This article assessed the main agribusiness opportunity costs for natural areas preservation: the land use profitability and the arable land price. The CDRA percentage and the opportunity costs were estimated for 349 municipal districts of So Paulo State through secondary spatial data and profitability values of 38 main agricultural products. We found that Brazilian private protected areas policy fails to preserve CDRA, although the values of non-compliance fines were higher than average opportunity costs. The scenario with very restrictive laws on private protected areas and historical high interest rates allowed us to conceive a feasible cross compliance proposal to improve environmental and agricultural policies.

Embryonic Development of Ampheres leucopheus and lporangaia pustulosa (Arachnida: Opiliones: Gonyleptidae)

The first studies concerning the embryonic development of harvestmen started in the late 19th century, and focused mostly on holarctic species, and only three species of the suborder Laniatores (the largest, among the four suborders considered presently) were studied. Moreover, the last studies on embryology of harvestmen were made during the late 1970s. This study focused on the embryonic development of Ampheres leucopheus (Gonyleptidae, Caelopyginae) and Iporangaia pustulosa (Gonyleptidae, Progonyleptoidellinae). The embryonic development was followed in the field, by taking daily photographs of different eggs during about 2 months. When laid, eggs of A. leucopheus and I pustulosa have approximately 1.13 and 1.30 mm in diameter, respectively, and the second is embedded in a large amount of mucus. The eggs grow, mainly due to water absorption at the beginning of the process, and they reach a diameter of about 1.35 and 1.59 mm, respectively, close to hatching. It took, respectively, 29-56 days and 35-66 days from egg laying to hatching. For the description of the embryonic development, we use photographs from the field, SEM micrographs, and histological analysis. This allowed us, for instance, to document the progression of structures and pigmentation directly from live embryos in the field, and to record microstructures, such as the presence of perforations in the cuticle of the embryo in the place where eyes are developing. Yet, contrary to what was expected in the literature, we record an egg tooth in one of the studied laniatoreans. J. Exp. Zool. (Mol. Dev. Evol) 314B:489-502, 2010. (C) 2010 Wiley-Liss, Inc.

A single-step procedure for the preparation of palladium nanoparticles and a phosphine-functionalized support as catalyst for Suzuki cross-coupling reactions

We here report the preparation of supported palladium nanoparticles (NPs) stabilized by pendant phosphine groups by reacting a palladium complex containing the ligand 2-(diphenylphosphino)benzaldehyde with an amino-functionalized silica surface The Pd nanocatalyst is active for Suzuki cross-coupling reaction avoiding any addition of other sources of phosphine ligands The Pd intermediates and Pd NPs were characterized by solid-state nuclear magnetic resonance and transmission electron microscopy techniques The synthetic method was also applied to prepare magnetically recoverable Pd NPs leading to a catalyst that could be reused for up to 10 recycles In summary we gathered the advantages of heterogeneous catalysis magnetic separation and enhanced catalytic activity of palladium promoted by phosphine ligands to synthesize a new catalyst for Suzuki cross-coupling reactions The Pd NP catalyst prepared on the phosphine-functionalized support was more active and selective than a similar Pd NP catalyst prepared on an amino-functionalized support (C) 2010 Elsevier Inc All rights reserved

Effect of SO(2) on the Transport Properties of an Imidazolium Ionic Liquid and Its Lithium Solution

Transport coefficients have been measured as a function of the concentration of sulfur dioxide, SO(2), dissolved in 1-butyl-2,3-dimethylimidazolium bis(trifluoromethylsulfonyl)-imide, [BMMI][Tf(2)N], as well as in its lithium salt solution, Li[Tf(2)N]. The SO(2) reduces viscosity and density and increases conductivity and diffusion coefficients in both the neat [BMMI] [Tf(2)N] and the [BMMI][Tf(2)N]-Li[Tf(2)N] solution. The conductivity enhancement is not assigned to a simple viscosity effect; the weakening of ionic interactions upon SO(2) addition also plays a role. Microscopic details of the SO(2) effect were unraveled using Raman spectroscopy and molecular dynamics (MD) simulations. The Raman spectra suggest that the Li(+)-[Tf(2)N] interaction is barely affected by SO(2), and the SO(2)-[Tf(2)N] interaction is weaker than previously observed in an investigation of an ionic liquid containing the bromide anion. Transport coefficients calculated by MD simulations show the same trend as the experimental data with respect to SO(2) content. The MD simulations provide structural information on SO(2) molecules around [Tf(2)N], in particular the interaction of the sulfur atom of SO(2) with oxygen and fluorine atoms of the anion. The SO(2)-[BMMI] interaction is also important because the [BMMI] cations with above-average mobility have a larger number of nearest-neighbor SO(2) molecules.