Cognitive, Mood, and Electroencephalographic Effects of Noninvasive Cortical Stimulation With Weak Electrical Currents

Objectives: The use of noninvasive cortical electrical stimulation with weak currents has significantly increased in basic and clinical human studies. Initial, preliminary studies with this technique have shown encouraging results; however, the safety and tolerability of this method of brain stimulation have not been sufficiently explored yet. The purpose of our study was to assess the effects of direct current (DC) and alternating current (AC) stimulation at different intensities in order to measure their effects on cognition, mood, and electroencephalogram. Methods: Eighty-two healthy, right-handed subjects received active and sham stimulation in a randomized order. We conducted 164 ninety-minute sessions of electrical stimulation in 4 different protocols to assess safety of (1) anodal DC of the dorsolateral prefrontal cortex (DLPFC); (2) cathodal DC of the DLPFC; (3) intermittent anodal DC of the DLPFC and; (4) AC on the zygomatic process. We used weak currents of 1 to 2 mA (for DC experiments) or 0.1 to 0.2 mA (for AC experiment). Results: We found no significant changes in electroencephalogram, cognition, mood, and pain between groups and a low prevalence of mild adverse effects (0.11% and 0.08% in the active and sham stimulation groups, respectively), mainly, sleepiness and mild headache that were equally distributed between groups. Conclusions: Here, we show no neurophysiological or behavioral signs that transcranial DC stimulation or AC stimulation with weak currents induce deleterious changes when comparing active and sham groups. This study provides therefore additional information for researchers and ethics committees, adding important results to the safety pool of studies assessing the effects of cortical stimulation using weak electrical currents. Further studies in patients with neuropsychiatric disorders are warranted.

The neuroimmune changes induced by cohabitation with an Ehrlich tumor-bearing cage mate rely on olfactory information

Cohabitation for 14 days with Ehrlich tumor-bearing mice was shown to increase locomotor activity, to decrease hypothalamic noradrenaline (NA) levels, to increase NA turnover and to decrease innate immune responses and decrease the animals' resistance to tumor growth. Cage mates of a B16F10 melanoma-bearer mice were also reported to show neuroimmune changes. Chemosignals released by Ehrlich tumor-bearing mice have been reported to be relevant for the neutrophil activity changes induced by cohabitation. The present experiment was designed to further analyze the effects of odor cues on neuroimmune changes induced by cohabitation with a sick cage mate. Specifically, the relevance of chemosignals released by an Ehrlich tumor-bearing mouse was assessed on the following: behavior (open-field and plus maze); hypothalamic NA levels and turnover; adrenaline (A) and NA plasmatic levels; and host resistance induced by tumor growth. To comply with such objectives, devices specifically constructed to analyze the influence of chemosignals released from tumor-bearing mice were employed. The results show that deprivation of odor cues released by Ehrlich tumor-bearing mice reversed the behavioral, neurochemical and immune changes induced by cohabitation. Mice use scents for intraspecies communication in many social contexts. Tumors produce volatile organic compounds released into the atmosphere through breath, sweat, and urine. Our results strongly suggest that volatile compounds released by Ehrlich tumor-injected mice are perceived by their conspecifics, inducing the neuroimmune changes reported for cohabitation with a sick companion. (C) 2011 Elsevier Inc. All rights reserved.

Fish Oil Supplementation Reduces Cachexia and Tumor Growth While Improving Renal Function in Tumor-Bearing Rats

The objective of the present work was to study the renal function of healthy and tumor-bearing rats chronically supplemented with fish oil (FO), a source of n-3 polyunsaturated fatty acids. Weanling male rats were divided in two groups, one control (C) and another orally supplemented for 70 days with FO (1 g/kg body weight). After this time, half the animals of each group were injected in the right flank with a suspension of Walker 256 tumor cells (W and WFO). The W group had less proteinemia reflecting cachectic proteolysis, FO reversed this fact. Tumor weight gain was also reduced in WFO. Glomerular filtration rate (GFR) was not different in FO or W compared to C, but was higher in WFO. Renal plasma flow (RPF) was higher in the FO supplemented groups. The W group had lower plasma osmolality than the C group, but FO supplementation resulted in normalization of this parameter. Fractional sodium excretion (FENa+) of FO rats was similar to C. Proximal Na+ reabsorption, evaluated by lithium clearance, was similar among the groups. Urinary thromboxane B-2 (TXB2) excretion was lower in the supplemented groups. The number of macrophages in renal tissue was higher in W compared to C rats, but was lower in WFO rats compared to W rats. In conclusion, FO supplementation resulted in less tumor growth and cachexia, and appeared to be renoprotective, as suggested by higher RPF and GFR.

Use of recent geoid models to estimate mean dynamic topography and geostrophic currents in South Atlantic and Brazil Malvinas confluence

The use of geoid models to estimate the Mean Dynamic Topography was stimulated with the launching of the GRACE satellite system, since its models present unprecedented precision and space-time resolution. In the present study, besides the DNSC08 mean sea level model, the following geoid models were used with the objective of computing the MDTs: EGM96, EIGEN-5C and EGM2008. In the method adopted, geostrophic currents for the South Atlantic were computed based on the MDTs. In this study it was found that the degree and order of the geoid models affect the determination of TDM and currents directly. The presence of noise in the MDT requires the use of efficient filtering techniques, such as the filter based on Singular Spectrum Analysis, which presents significant advantages in relation to conventional filters. Geostrophic currents resulting from geoid models were compared with the HYCOM hydrodynamic numerical model. In conclusion, results show that MDTs and respective geostrophic currents calculated with EIGEN-5C and EGM2008 models are similar to the results of the numerical model, especially regarding the main large scale features such as boundary currents and the retroflection at the Brazil-Malvinas Confluence.

Boron uptake in normal melanocytes and melanoma cells and boron biodistribution study in mice bearing B16F10 melanoma for boron neutron capture therapy

Information on B-10 distribution in normal tissues is crucial to any further development of boron neutron capture therapy (BNCT). The goal of this study was to investigate the in vitro and in vivo boron biodistribution in B16F10 murine melanoma and normal tissues as a model for human melanoma treatment by a simple and rapid colorimetric method, which was validated by HR-ICP-MS. The B16F10 melanoma cell line showed higher melanin content than human melanocytes, demonstrating a greater potential for boronophenylalanine uptake. The melanocytes showed a moderate viability decrease in the first few minutes after BNCT application, stabilizing after 75 min, whereas the B16F10 melanoma showed the greatest intracellular boron concentration at 150 min after application, indicating a different boron uptake of melanoma cells compared to normal melanocytes. Moreover, at this time, the increase in boron uptake in melanoma cells was approximately 1.6 times higher than that in normal melanocytes. The B-10 concentration in the blood of mice bearing B16F10 melanoma increased until 90 min after BNCT application and then decreased after 120 min, and remained low until the 240th minute. On the other hand, the B-10 concentration in tumors was increased from 90 min and maximal at 150 min after application, thus confirming the in vitro results. Therefore, the present in vitro and in vivo study of B-10 uptake in normal and tumor cells revealed important data that could enable BNCT to be possibly used as a treatment for melanoma, a chemoresistant cancer associated with high mortality.

Reversible polymerization of novel monomers bearing furan and plant oil moieties: a double click exploitation of renewable resources

Monomers based on plant oil derivatives bearing furan heterocycles appended through thiol-ene click chemistry were prepared and, subsequently, polymerized via a second type of click reaction, i. e. the Diels-Alder (DA) polycondensation between furan and maleimide complementary moieties. Two basic approaches were considered for these DA polymerizations, namely (i) the use of monomers with two terminal furan rings in conjunction with bismaleimides (AA + BB systems) and (ii) the use of a protected AB monomer incorporating both furan and maleimide end groups. This study clearly showed that both strategies were successful, albeit with different outcomes, in terms of the nature of the ensuing products. The application of the retro-DA reaction to these polymers confirmed their thermoreversible character, i. e. the clean-cut return to their respective starting monomers, opening the way to original macromolecular materials with interesting applications, like mendability and recyclability.

Synthetic phosphoethanolamine a precursor of membrane phospholipids reduce tumor growth in mice bearing melanoma B16-F10 and in vitro induce apoptosis and arrest in G2/M phase

Phosphoethanolamine (Pho-s) is a compound involved in phospholipid turnover, acting as a substrate for many phospholipids of the cell membranes, especially phosphatidylcholine. We recently reported that synthetic Pho-s has potent effects on a wide variety of tumor cells. To determine if Pho-s has a potential antitumor activity, in this study we evaluated the activity of Pho-s against the B16-F10 melanoma both in vitro and in mice bearing a dorsal tumor. The treatment of B16F10 cells with Pho-s resulted in a dose-dependent inhibition of cell proliferation. At low concentrations, this activity appears to be involved in the arrest of the cell cycle at G2/M, while at high concentrations Pho-s induces apoptosis. In accordance with these results, the loss of mitochondrial potential and increased caspase-3 activity suggest that Phos has dual antitumor effects; i.e. it induces apoptosis at high concentrations and modulates the cell cycle at lower concentrations. In vivo, we evaluated the effect of Pho-s in mice bearing B16-F10 melanoma. The results show that Pho-s reduces the tumoral volume increasing survival rate. Furthermore, the tumor doubling time and tumor delays were substantially reduced when compared with untreated mice. Histological analyses reveal that Pho-s induces changes in cell morphology, typical characteristics of apoptosis, in addition the large areas of necrosis correlating with a reduction of tumor size. The results presented here support the hypothesis that Pho-s has antitumor effects by the induction of apoptosis as well as the inhibition of cell proliferation by arrest at G2/M. Thus, Pho-s can be regarded as a promising agent for the treatment of melanoma. Published by Elsevier Masson SAS.

Theophylline is able to partially revert cachexia in tumour-bearing rats

Abstract Background and aims The aim of the present investigation was to examine the anti-wasting effects of theophylline (a methylxantine present in tea leaves) on a rat model of cancer cachexia. Methods The in vitro effects of the nutraceuticals on proteolysis were examined on muscle cell cultures submitted to hyperthermia. Individual muscle weights, muscle gene expression, body composition and cardiac function were measured in rats bearing the Yoshida AH-130 ascites hepatoma, following theophylline treatment. Results Theophylline treatment inhibited proteolysis in C2C12 cell line and resulted in an anti-proteolytic effect on muscle tissue (soleus and heart), which was associated with a decrease in circulating TNF-alpha levels and with a decreased proteolytic systems gene expression. Treatment with the nutraceutical also resulted in an improvement in body composition and cardiac function. Conclusion Theophylline - alone or in combination with drugs - may be a candidate molecule for the treatment of cancer cachexia.

Use of recent geoid models to estimate mean dynamic topography and geostrophic currents in South Atlantic and Brazil Malvinas confluence

The use of geoid models to estimate the Mean Dynamic Topography was stimulated with the launching of the GRACE satellite system, since its models present unprecedented precision and space-time resolution. In the present study, besides the DNSC08 mean sea level model, the following geoid models were used with the objective of computing the MDTs: EGM96, EIGEN-5C and EGM2008. In the method adopted, geostrophic currents for the South Atlantic were computed based on the MDTs. In this study it was found that the degree and order of the geoid models affect the determination of TDM and currents directly. The presence of noise in the MDT requires the use of efficient filtering techniques, such as the filter based on Singular Spectrum Analysis, which presents significant advantages in relation to conventional filters. Geostrophic currents resulting from geoid models were compared with the HYCOM hydrodynamic numerical model. In conclusion, results show that MDTs and respective geostrophic currents calculated with EIGEN-5C and EGM2008 models are similar to the results of the numerical model, especially regarding the main large scale features such as boundary currents and the retroflection at the Brazil-Malvinas Confluence.

Cement-base bearing pads mortar for connections in the precast concrete: study of surface roughness

Bearing pads are used in precast concrete connections to avoid concentrated stresses in the contact area between the precast elements. In the present research, the bearing pads are Portland cement mortar with styrene-butadiene latex (SB), lightweight aggregate (expanded vermiculite-term) and short fibers (polypropylene, glass and PVA), in order to obtain a material with low modulus of elasticity and high tenacity, compared with normal Portland cement mortar. The objective of this paper is to analyze the influence of surface roughness on the pads and test other types of polypropylene fibers. Tests were carried out to characterize the composite and test on bearing pads. Characterization tests show compressive strength of 41MPa and modulus of elasticity of 12.8GPa. The bearing pads tests present 30% reduction of stiffness in relation to a reference mortar. The bearing pads with roughness on both sides present a reduction up to 30% in stiffness and an increase in accumulated deformation of more than 120%, regarding bearing pads with both sides smooth.

Currents controlling sedimentation, deposits recording palaeo-hydrodynamics – lessons from the continental shelf-slope system off SE South America

The continental margin off SE South America hosts one of the world’s most energetic hydrodynamic regimes but also the second largest drainage system of the continent. Both, the ocean current system as well as the fluvial runoff are strongly controlled by the atmospheric circulation modes over the region. The distribution pattern of particular types of sediments on shelf and slope and the long-term built-up of depositional elements within the overall margin architecture are, thus, the product of both, seasonal to millennial variability as well as long-term environmental trends. This talk presents how the combination of different methodological approaches can be used to obtain a comprehensive picture of the variability of a shelf and upper-slope hydrodynamic system during Holocene times. The particular methods applied are: (a) Margin-wide stratigraphic information to elucidate the role of sea level for the oceanographic and sedimentary systems since the last glacial maximum; (b) Palaeoceanographic sediment proxies combined with palaeo-temperature indicating isotopes of bivalve shells to trace lateral shifts in the coastal oceanography (particularly of the shelf front) during the Holocene; (c) Neodymium isotopes to identify the shelf sediment transport routes resulting from the current regime; (d) Sedimentological/geochemical data to show the efficient mechanism of sand export from the shelf to the open ocean; (e) Diatom assemblages and sediment element distributions indicating palaeo-salinity and the changing marine influence to illustrate the Plata runoff history. Sea level has not only controlled the overall configuration of the shelf but also the position of the main sediment routes from the continent towards the ocean. The shelf front has shifted frequently since the last glacial times probably resulting from both, changes in the Westerly Winds intensity and in the shelf width itself. Remarkable is a southward shift of this front during the past two centuries possibly related to anthropogenic influences on the atmosphere. The oceanographic regime with its prominent hydrographic boundaries led to a clear separation of sedimentary provinces since shelf drowning. It is especially the shelf front which enhances shelf sediment export through a continuous high sand supply to the uppermost slope. Finally, the Plata River does not continuously provide sediment to the shelf but shows significant climate-related changes in discharge during the past centuries. Starting from these findings, three major fields of research should, in general, be further developed in future: (i) The immediate interaction of the hydrodynamic and sedimentary systems to close the gaps between deposit information and modern oceanographic dynamics; (ii) Material budget calculations for the marginal ocean system in terms of material fluxes, storage/retention capacities, and critical thresholds; (iii) The role of human activity on the atmospheric, oceanographic and solid material systems to unravel natural vs. anthropogenic effects and feedback mechanisms