Immunomodulatory effects of low dose chemotherapy and perspectives of combanation with immunotherapy

Nowadays cancer is one of the main causes of death and many efforts worldwide have been driven to find out new treatments and approaches in order to extinguish or reduce this group of disorder. Chemotherapy is the main treatment for cancer, however, conventional schedule based on maximum tolerated dose (MTD) show several side effects and frequently allow the development of drug resistance. In this review we present the evidence that metronomic chemotherapy, based on the frequent administration of low or intermediate doses of chemotherapeutics is as efficient as MTD and works better in some situations. Finally, we present some data indicating that noncytotoxic concentrations of antineoplastic agents are able to both up-regulate the immune system and increase the susceptibility of tumor cells to cytotoxic T lymphocytes. Taken together, data from the literature provide us the evidence that low concentrations of selected chemotherapeutics agents, rather than conventional high doses, should be chosen for combination with immunotherapy

Aplicação de fósforo e potássio na implantação de Corymbia citriodora (Hook.) K. D. Hill & L. A. S. Johnson

Pós-graduação em Agronomia (Produção Vegetal) - FCAV

Galectin-1 exerts inhibitory effects during DENV-1 infection

Dengue virus (DENV) is an enveloped RNA virus that is mosquito-transmitted and can infect a variety of immune and non-immune cells. Response to infection ranges from asymptomatic disease to a severe disorder known as dengue hemorrhagic fever. Despite efforts to control the disease, there are no effective treatments or vaccines. In our search for new antiviral compounds to combat infection by dengue virus type 1 (DENV-1), we investigated the role of galectin-1, a widely-expressed mammalian lectin with functions in cell-pathogen interactions and immunoregulatory properties. We found that DENV-1 infection of cells in vitro exhibited caused decreased expression of Gal-1 in several different human cell lines, suggesting that loss of Gal-1 is associated with virus production. In test of this hypothesis we found that exogenous addition of human recombinant Gal-1 (hrGal-1) inhibits the virus production in the three different cell types. This inhibitory effect was dependent on hrGal-1 dimerization and required its carbohydrate recognition domain. Importantly, the inhibition was specific for hrGal-1, since no effect was observed using recombinant human galectin-3. Interestingly, we found that hrGal-1 directly binds to dengue virus and acts, at least in part, during the early stages of DENV-1 infection, by inhibiting viral adsorption and its internalization to target cells. To test the in vivo role of Gal-1 in DENV infection, Gal-1-deficient-mice were used to demonstrate that the expression of endogenous Galectin-1 contributes to resistance of macrophages to in vitro-infection with DENV-1 and it is also important to physiological susceptibility of mice to in vivo infection with DENV-1. These results provide novel insights into the functions of Gal-1 in resistance to DENV infection and suggest that Gal-1 should be explored as a potential antiviral compound.

Galectin-1 exerts inhibitory effects during DENV-1 infection

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Local order and magnetic field effects on the electronic properties of disordered binary alloys in the quantum site percolation limit

Electronic properties of disordered binary alloys are studied via the calculation of the average Density of States (DOS) in two and three dimensions. We propose a new approximate scheme that allows for the inclusion of local order effects in finite geometries and extrapolates the behavior of infinite systems following finite-size scaling ideas. We particularly investigate the limit of the Quantum Site Percolation regime described by a tight-binding Hamiltonian. This limit was chosen to probe the role of short range order (SRO) properties under extreme conditions. The method is numerically highly efficient and asymptotically exact in important limits, predicting the correct DOS structure as a function of the SRO parameters. Magnetic field effects can also be included in our model to study the interplay of local order and the shifted quantum interference driven by the field. The average DOS is highly sensitive to changes in the SRO properties and striking effects are observed when a magnetic field is applied near the segregated regime. The new effects observed are twofold: there is a reduction of the band width and the formation of a gap in the middle of the band, both as a consequence of destructive interference of electronic paths and the loss of coherence for particular values of the magnetic field. The above phenomena are periodic in the magnetic flux. For other limits that imply strong localization, the magnetic field produces minor changes in the structure of the average DOS. © World Scientific Publishing Company.

Effects of β-(1→3,1→6)-d-glucan and density of diets on the blood profiles of immunologically challenged weaned piglets

An experiment was conducted to evaluate the effects of two levels of the β-(1→3,1→6)-d-glucan (0 and 500ppm) from yeast Saccharomyces cerevisiae and two levels of energy (3300 and 3450kcalMEkg(-1)) on the hematological, immunological and, biochemical profiles of thirty-six 21-days-old weaned piglets, challenged with 150μgkg(-1) of BW lipopolysaccharide (LPS) from Escherichia coli serotype 055:B5. The experimental design was a randomized complete block design in a 2×2 factorial arrangement with nine replicates per treatment and, one animal per experimental unit. The data were analyzed in accordance with the multivariate analysis procedure of SAS and, the treatment means of parametric and non-parametric data were compared by Bonferroni's test (P<0.05) and, by Dunn's test (P<0.05), respectively. The data of the blood profiles of alanine aminotransferase, alkaline phosphatase and, creatinine showed that LPS did not cause kidney or liver damage in the animals. The addition of beta-glucan in the diets did not prove the robustness of its effect and biological relevance when provided with low nutrient-density. However, its addition combined with the high-nutrient-density diets showed less marked hypoglobulinemia in piglets, which may have contributed to the decreasing of the synthesis of inflammatory mediators.

Differences in larval nutritional requirements and female oviposition preference reflect the order of fruit colonization of Zaprionus indianus and Drosophila simulans

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Phase transition from a d(x(2)-y(2)) to d(x(2)-y(2))+id(xy) superconductor

The temperature dependencies of specific heat and spin susceptibility of a coupled dx2-y2 + idxy superconductor in the presence of a weak dxy component are investigated in the tight-binding model (1) on square lattice and (2) on a lattice with orthorhombic distortion. As the temperature is lowered past the critical temperature Tc, first a less ordered dx2-y2 superconductor is created, which changes to a more ordered dx2-y2 + idxy superconductor at Tcl(< Tc). This manifests in two second order phase transitions identified by two jumps in specific heat at Tc and Tc1. The temperature dependencies of the superconducting observables exhibit a change from power-law to exponential behavior as temperature is lowered below Tc1 and confirm the new phase transition. © 1998 Published by Elsevier Science B.V. All rights reserved.

Analyse du processus d'inclusion d'un élève avec déficience physique en cours d'éducation physique: étude de cas

The aim of this study was to evaluate the effects of peer tutor teaching strategy, after a re-training, in relation to the inclusion process of a student with physical disability during physical education classes. The participants were: the student with physical disability, eight peer tutors, and a physical education teacher of a public school in Bauru, Brazil. As the students had previously experienced the tutoring training, a re-training was prepared, which enabled the reinforcement of some aspects of the tutoring and assistance strategies, in order to improve the tutor colleague action. To analyze, two observation instruments were used: System for Observing Fitness Instruction Time (SOFIT) and Souza Observation Protocol. Behavioral changes of the involved students were notable, due to the significant action of the re-training process. Thus, we highlight the importance of the periodic reinforcements of the training for the tutor colleagues, in order to preserve, or even improve the autonomy and self-esteem of the student with disability.

Efeitos de formulações e intervalos sem chuva na absorção, translocação e eficácia de Glyphosate e 2,4-D

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Effects in mechanical properties and structure of the soil after tillage with rotary paraplow

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Onset of Conduct Disorder, Use of Delinquent Subsistence Strategies, and Street Victimization among Homeless and Runaway Adolescents in the Midwest

This study examines the effects of childhood-onset conduct disorder on later antisocial behavior and street victimization among a group of homeless and runaway adolescents. Four hundred twenty-eight homeless and runaway youth were interviewed directly on the streets and in shelters from four Midwestern states. Key findings include the following. First, compared with those who exhibit adolescent-onset conduct disorder, youth with childhood onset are more likely to engage in a series of antisocial behaviors such as use of sexual and nonsexual survival strategies. Second, youth with childhood-onset conduct disorder are more likely to experience violent victimization; this association, however, is mostly through an intervening process such as engagement in deviant survival strategies.

Effects of different cryopreservation methods on post-thaw culture conditions of in vitro produced bovine embryos

The aim of this work was to evaluate the effect of cryopreservation protocols on subsequent development of in vitro produced bovine embryos under different culture conditions. Expanded in vitro produced blastocysts (n = 600) harvested on days 7-9 were submitted to controlled freezing [slow freezing group: 10% ethylene glycol (EG) for 10 min and 1.2 degrees C/min cryopreservation]; quick-freezing [rapid freezing group: 10% EG for 10 min, 20% EG + 20% glycerol (Gly) for 30 s]; or vitrification [vitrification group: 10% EG for 10 min, 25% EG + 25% Gly for 30 s] protocols. Control group embryos were not exposed to cryoprotectant or cryopreservation protocols and the hatching rate was evaluated on day 12 post-insemination. In order to evaluate development, frozen-thawed embryos were subjected to granulosa cell co-culture in TCM199 or SOFaa for 4 days. Data were analyzed by PROC MIXED model using SAS Systems for Windows (R). Values were significant at p < 0.05. The hatching rate of the control group was 46.09%. In embryos cultured in TCM199, slow freezing and vitrification group hatching rates were 44.65 +/- 5.94% and 9.43 +/- 6.77%, respectively. In embryos cultured in SOFaa, slow freezing and vitrification groups showed hatching rates of 11.65 +/- 3.37 and 8.67 +/- 4.47%, respectively. In contrast, the rapid freezing group embryos did not hatch, regardless of culture medium. The slow freezing group showed higher hatching rates than other cryopreservation groups. Under such conditions, controlled freezing (1.2 degrees C/min) can be an alternative to cryopreservation of in vitro produced bovine embryos.

Late Adverse Effects of the Coadministration of Valproate and Lamotrigine

Individuals treated with combined valproate-lamotrigine rarely present late adverse effects (unrelated to introduction and titration). We describe four patients in whom such effects occurred after continuous, long-term use of valproate-lamotrigine (at 9 months to 2 years after final antiepileptic drug adjustment). The patients presented heterogeneous disturbances, including ataxia, vertigo, and headache, and rare movement disorders, such as tics and abnormal eye movements. Although these effects are heterogeneous in their occurrence and timing, they can alert physicians to the possibility of late neurologic disturbances, and must be considered in order to avoid unnecessary ancillary tests. Treatment discontinuation is unnecessary, given that a small decrease in dose led to remission of these adverse effects. (c) 2012 Elsevier Inc. All rights reserved.

Gray Matter Volumes in Obsessive-Compulsive Disorder Before and After Fluoxetine or Cognitive-Behavior Therapy: A Randomized Clinical Trial

Serotonin reuptake inhibitors and cognitive-behavior therapy (CBT) are considered first-line treatments for obsessive-compulsive disorder (OCD). However, little is known about their modulatory effects on regional brain morphology in OCD patients. We sought to document structural brain abnormalities in treatment-naive OCD patients and to determine the effects of pharmacological and cognitive-behavioral treatments on regional brain volumes. Treatment-naive patients with OCD (n = 38) underwent structural magnetic resonance imaging scan before and after a 12-week randomized clinical trial with either fluoxetine or group CBT. Matched-healthy controls (n = 36) were also scanned at baseline. Voxel-based morphometry was used to compare regional gray matter (GM) volumes of regions of interest (ROIs) placed in the orbitofrontal, anterior cingulate and temporolimbic cortices, striatum, and thalamus. Treatment-naive OCD patients presented smaller GM volume in the left putamen, bilateral medial orbitofrontal, and left anterior cingulate cortices than did controls (p<0.05, corrected for multiple comparisons). After treatment with either fluoxetine or CBT (n = 26), GM volume abnormalities in the left putamen were no longer detectable relative to controls. ROI-based within-group comparisons revealed that GM volume in the left putamen significantly increased (p<0.012) in fluoxetine-treated patients (n = 13), whereas no significant GM volume changes were observed in CBT-treated patients (n = 13). This study supports the involvement of orbitofronto/cingulo-striatal loops in the pathophysiology of OCD and suggests that fluoxetine and CBT may have distinct neurobiological mechanisms of action. Neuropsychopharmacology (2012) 37, 734-745; doi: 10.1038/npp.2011.250; published online 26 October 2011