946 resultados para BCG immunotherapy
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Nowadays, with the implantation of GNSS (Global Navigation Satellite System) reference station networks, several positioning techniques have been developed and/or improved. Using such kind of network data it is possible to model the GNSS distance dependent errors and to compute correction terms for the network region. Several methods have been developed to formulate the corrections terms from network stations data. A method that has been received a great attention is the Virtual Reference Station (VRS). The idea is that the VRS data resemble as much as possible a real receiver data placed in the same local. Therefore, the user has the possibility of using the VRS as if it were a real reference station in your proximities, and to accomplish the relative positioning with a single frequency receiver. In this paper it is described a different methodology applied to implement the VRS concept, using atmospheric models developed by Brazilian researchers. Besides, experiments for evaluating the quality of generated VRS are presented, showing the efficiency of the proposed method.
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Mice genetically selected for high (H) and low (L) antibody production (Selection IV-A) were used as murine experimental model. The aim of the present work was to evaluate the macrophagic activity and to characterize the immune response in Mycobacterium bovis-AN5 infected mice (3×10 7 bacteria). The response profile previously observed in such strains was not similar to that obtained during M. bovis infection; however, it corroborated works carried out using Selection I, which is very similar to Selection IV-A regarding infection by M. tuberculosis and Bacillus Calmette-Guérin (BCG). Considering bacterial recovery, LIV-A mice showed higher control of the infectious process in the lungs than in the spleen, whereas HIV-A mice presented more resistance in the spleen. With respect to macrophagic activity, hydrogen peroxide (H2O 2) was probably not involved in the infection control since there was an inhibition in the production of this metabolite. Nitric oxide (NO) and TNF-α production seemed to be important in the control of bacterial replication and varied according to the strain, period and organ. Evaluation of the antibody production indicated that the multi-specific effect commonly observed in these strains was not the same in the response to M. bovis. Antibody concentrations were higher in LIV-A than in HIV-A mice at the beginning of the infection, being similar afterwards. Such data were compared with delayed-type hypersensitivity (DTH), which was more intense in HIV-A than in LIV-A mice, indicating that antibody production is independent of the capability to trigger DTH reactions and that cellular and humoral responses to M. bovis antigens show a polygenic control and an independent quantitative genetic regulation. Differences were observed among organs and metabolites, suggesting that different mechanisms play an important role in this infection in natural heterogeneous populations, indicating that NO, TNF-α and Th1 cytokines are involved in the infection control.
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Background: Vaccination of neonates is generally difficult due to the immaturity of the immune system and consequent higher susceptibility to tolerance induction. Genetic immunization has been described as an alternative to trigger a stronger immune response in neonates, including significant Th1 polarization. In this investigation we analysed the potential use of a genetic vaccine containing the heat shock protein (hsp65) from Mycobacterium leprae (pVAXhsp65) against tuberculosis (TB) in neonate mice. Aspects as antigen production, genomic integration and immunogenicity were evaluated. Methods: Hsp65 message and genomic integration were evaluated by RT-PCR and Southern blot, respectively. Immunogenicity of pVAXhsp65 alone or combined with BCG was analysed by specific induction of antibodies and cytokines, both quantified by ELISA. Results: This DNA vaccine was transcribed by muscular cells of neonate mice without integration into the cellular genome. Even though this vaccine was not strongly immunogenic when entirely administered (three doses) during early animal's life, it was not tolerogenic. In addition, pVAXhsp65 and BCG were equally able to prime newborn mice for a strong and mixed immune response (Th1 + Th2) to pVAXhsp65 boosters administered later, at the adult life. Conclusion: These results suggest that pVAXhsp65 can be safely used as a priming stimulus in neonate animals in prime-boost similar strategies to control TB. However, priming with BCG or pVAXhsp65, directed the ensuing immune response triggered by an heterologous or homologous booster, to a mixed Th1/Th2 pattern of response. Measures as introduction of IL-12 or GM-CSF genes in the vaccine construct or even IL-4 neutralization, are probably required to increase the priming towards Th1 polarization to ensure control of tuberculosis infection. © 2007 Pelizon et al; licensee BioMed Central Ltd.
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The Brazilian Geodetic Network started to be established in the early 40's, employing classical surveying methods, such as triangulation and trilateration. With the introduction of satellite positioning systems, such as TRANSIT and GPS, that network was densified. That data was adjusted by employing a variety of methods, yielding distortions in the network that need to be understood. In this work, we analyze and interpret study cases in an attempt to understand the distortions in the Brazilian network. For each case, we performed the network adjustment employing the GHOST software suite. The results show that the distortion is least sensitive to the removal of invar baselines in the classical network. The network would be more affected by the inexistence of Laplace stations and Doppler control points, with differences up to 4.5 m.
Infantile epileptic encephalopathy with hypsarrhythmia (infantile spasms/west syndrome) and immunity
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West syndrome is a severe epilepsy, occurring in infancy, that comprises epileptic seizures known as spasms, in clusters, and a unique EEG pattern, hypsarrhythmia, with psychomotor regression. Maturation of the brain is a crucial component. The onset is within the first year of life, before 12 months of age. Patients are classified as cryptogenic (10 to 20%), when there are no known or diagnosed previous cerebral insults, and symptomatic (80 to 90%), when associated with pre-existing cerebral damages. The time interval from a brain insult to infantile spasms onset ranged from 6 weeks to 11 months. West syndrome has a time-limited natural evolutive course, usually disappearing by 3 or 4 years of age. In 62% of patients, there are transitions to another age-related epileptic encephalopathies, the Lennox-Gastaut Syndrome and severe epilepsy with multiple independent foci. Spontaneous remission and remission after viral infections may occur. Therapy with ACTH and corticosteroids are the most effective. Reports about intravenous immunoglobulins action deserve attention. There is also immune dysfunction, characterized mainly by anergy, impaired cell-mediated immunity, presence of immature thymocytes in peripheral blood, functional impairment of T lymphocytes induced by plasma inhibitory factors, and altered levels of immunoglobulins. Changes in B lymphocytes frequencies and increased levels of activated B cells have been reported. Sensitized lymphocytes to brain extract were also described. Infectious diseases are frequent and may, sometimes, cause fatal outcomes. Increase of pro-inflamatory cytokines in serum and cerebrospinal fluid of epileptic patients were reported. Association with specific HLA antigens was described by several authors (HLA-DR7, HLA-A7, HLA-DRw52, and HLA-DR5). Auto-antibodies to brain antigens, of several natures (N-methyl-d-aspartate glutamate receptor, gangliosides, brain tissue extract, synaptic membrane, and others), were described in epileptic patients and in epileptic syndromes. Experimental epilepsy studies with anti-brain antibodies demonstrated that epileptiform discharges can be obtained, producing hyperexcitability leading to epilepsy. We speculate that in genetically prone individuals, previous cerebral lesions may sensitize immune system and trigger an autoimmune disease. Antibody to brain antigens may be responsible for impairment of T cell function, due to plasma inhibitory effect and also cause epilepsy in immature brains. © 2008 Bentham Science Publishers Ltd.
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Background: Our group previously demonstrated that a DNA plasmid encoding the mycobacterial 65-kDa heat shock protein (DNA-HSP65) displayed prophylactic and therapeutic effect in a mice model for tuberculosis. This protection was attributed to induction of a strong cellular immunity against HSP65. As specific immunity to HSP60 family has been detected in arthritis, multiple sclerosis and diabetes, the vaccination procedure with DNA-HSP65 could induce a cross-reactive immune response that could trigger or worsen these autoimmune diseases. Methods: In this investigation was evaluated the effect of a previous vaccination with DNA-HSP65 on diabetes development induced by Streptozotocin (STZ). C57BL/6 mice received three vaccine doses or the corresponding empty vector and were then injected with multiple low doses of STZ. Results: DNA-HSP65 vaccination protected mice from STZ induced insulitis and this was associated with higher production of IL-10 in spleen and also in the islets. This protective effect was also concomitant with the appearance of a regulatory cell population in the spleen and a decreased infiltration of the islets by T CD8+ lymphocytes. The vector (DNAv) also determined immunomodulation but its protective effect against insulitis was very discrete. Conclusion: The data presented in this study encourages a further investigation in the regulatory potential of the DNA-HSP65 construct. Our findings have important implications for the development of new immune therapy strategies to combat autoimmune diseases. © 2009 Santos et al; licensee BioMed Central Ltd.
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In the Brazil, several have been the applications of GPS and with the introduction of the Law 10.267/2001 that among other dispositions, it treats of the georeferencing of the rural parcels. However, most of the commercial softwares of processing and adjustment of GPS data doesn't allow that the users may evaluate their results in a reliable way. For example, the constraints are normally used as absolute, which provides results with very optimists precisions. The adoption of additional analyses and the implementation of softwares can reduce these kinds of problems. Thus, it was developed a software for adjustment of GPS networks, aiming to assist in a reliable way the requirements of the Law 10.267/2001. In this context, in this work it is analyzed the adjustments of GPS networks, utilizing absolute and relative constraints. In the case of the last one, the adjustments were accomplished considering and not considering the correlations among the coordinate positions.
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GPS active networks are more and more used in geodetic surveying and scientific experiments, as water vapor monitoring in the atmosphere and lithosphere plate movement. Among the methods of GPS positioning, Precise Point Positioning (PPP) has provided very good results. A characteristic of PPP is related to the modeling and / or estimation of the errors involved in this method. The accuracy obtained for the coordinates can reach few millimeters. Seasonal effects can affect such accuracy if they are not consistent treated during the data processing. Coordinates time series analyses have been realized using Fourier or Harmonics spectral analyses, wavelets, least squares estimation among others. An approach is presented in this paper aiming to investigate the seasonal effects included in the stations coordinates time series. Experiments were carried out using data from stations Manaus (NAUS) and Fortaleza (BRFT) which belong to the Brazilian Continuous GPS Network (RBMC). The coordinates of these stations were estimated daily using PPP and were analyzed through wavelets for identification of the periods of the seasonal effects (annual and semi-annual) in each time series. These effects were removed by means of a filtering process applied in the series via the least squares adjustment (LSQ) of a periodic function. The results showed that the combination of these two mathematical tools, wavelets and LSQ, is an interesting and efficient technique for removal of seasonal effects in time series.
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Some modifying factors may determine the risk of brain tumors. Until now, it could not be attempted to identify people at risk and also to improve significantly disease progression. Current therapy consists of surgical resection, followed by radiation therapy and chemotherapy. Despite of these treatments, the prognosis for patients is poor. In this review, we highlight general aspects concerning genetic alterations in brain tumors, namely astrocytomas, glioblastomas, oligodendrogliomas, medulloblastomas and ependymomas. The influence of these genetic alterations in patients' prognosis is discussed. Mutagen sensivity is associated with cancer risk. The convincing studies that linked DNA damages and DNA repair alterations with brain tumors are also described. Another important modifying factor is immunity. General immune response against cancer, tumor microenvironment and immune response, mechanisms of tumor escape, CNS tumor immunology, immune defects that impair anti-tumor systemic immunity in brain tumor patients and local immunosuppressive factors within CNS are also reviewed. New hope to treatment perspectives, as dendritic-cell-based vaccines is summarized too. Concluding, it seems well established that there is association between brain tumor risk and mutagen sensivity, which is highly heritable. Primary brain tumors cause depression in systemic host immunity; local immunosuppressive factors and immunological characteristics of tumor cells may explain the poor prognosis and DNA damages responses can alert immune system. However, it is necessary to clarify if individuals with both constitutional defects in immune functions and genetic instability have higher risk of developing brain tumors. Cytogenetic prospective studies and gene copy number variations analysis also must be performed in peripheral lymphocytes from brain tumor patients. © 2011 Bentham Science Publishers Ltd.
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Albumin concentrations in female Bronze turkeys were compared using agarose gel electrophoresis (AGE) and the bromocresol green (BCG) dye-binding method. The correlation coefficient observed for albumin in the BCG and AGE methods was low, and statistical differences were observed at paired t test (p < 0. 0001). Compared with electrophoresis, the BCG-binding method yielded significantly lower albumin values for female turkeys during laying season. © 2011 Springer-Verlag London Limited.
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The purpose of this study was to compare albumin concentrations in ring-necked pheasants (Phasianus colchicus) using two different dye-binding methods: the bromocresol green (BCG) and bromocresol purple (BCP). High positive correlation was observed for albumin in BCG and BCP methods. Compared to BCP, the BCG-binding method yielded significantly higher (p < 0. 0001) albumin values for adult female ring-necked pheasants. © 2012 Springer-Verlag London Limited.
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In this study, we describe the cDNA cloning, sequencing, and 3-D structure of the allergen hyaluronidase from Polybia paulista venom (Pp-Hyal). Using a proteomic approach, the native form of Pp-Hyal was purified to homogeneity and used to produce a Pp-specific polyclonal antibody. The results revealed that Pp-Hyal can be classified as a glycosyl hydrolase and that the full-length Pp-Hyal cDNA (1315 bp; GI: 302201582) is similar (80-90%) to hyaluronidase from the venoms of endemic Northern wasp species. The isolated mature protein is comprised of 338 amino acids, with a theoretical pI of 8.77 and a molecular mass of 39,648.8 Da versus a pI of 8.13 and 43,277.0 Da indicated by MS. The Pp-Hyal 3D-structural model revealed a central core (α/β)7 barrel, two sulfide bonds (Cys 19-308 and Cys 185-197), and three putative glycosylation sites (Asn79, Asn187, and Asn325), two of which are also found in the rVes v 2 protein. Based on the model, residues Ser299, Asp107, and Glu109 interact with the substrate and potential epitopes (five conformational and seven linear) located at surface-exposed regions of the structure. Purified native Pp-Hyal showed high similarity (97%) with hyaluronidase from Polistes annularis venom (Q9U6V9). Immunoblotting analysis confirmed the specificity of the Pp-Hyal-specific antibody as it recognized the Pp-Hyal protein in both the purified fraction and P. paulista crude venom. No reaction was observed with the venoms of Apis mellifera, Solenopsis invicta, Agelaia pallipes pallipes, and Polistes lanio lanio, with the exception of immune cross-reactivity with venoms of the genus Polybia (sericea and ignobilis). Our results demonstrate cross-reactivity only between wasp venoms from the genus Polybia. The absence of cross-reactivity between the venoms of wasps and bees observed here is important because it allows identification of the insect responsible for sensitization, or at least of the phylogenetically closest insect, in order to facilitate effective immunotherapy in allergic patients. © 2013 Elsevier Ltd.
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A clinical epidemiological study was conducted among 34 rural properties located within the Brazilian Pantanal region and nearby areas between 2007 and 2010. The diagnosis of equine pythiosis was based on antibody detection (by enzyme-linked immunosorbent assay), polymerase chain reaction, histopathological analysis, and cultures positive for Pythium insidiosum. The majority of the affected animals (85%) were in the Pantanal biome, which had a higher disease prevalence (0.9%-66.7%) than that of the Cerrado (2.7%-33.3%). The disease was more prevalent in the rainy season (January-March), with an abrupt fall in the number of cases during the drought period (April-September; correlation of R 2 = 0.77; P < .01). Generally, the average prevalence of equine pythiosis in both regions was 5%, with mortality and lethality rates of 1.3% and 23.1%, respectively, in the Pantanal and 2.3% and 45.5%, respectively, in the Cerrado. However, the treatment with immunotherapy may have underestimated these numbers, especially in the Pantanal. Animals older than 1 year were 8.09 times more affected by the disease than younger animals in the same environment (P < .05). A correlation between the anatomical area of the lesion and the type of skin color was also observed. Approximately 73% of the lesions were found in dark-pigmented areas, and animals with a dark coat color were affected more frequently. These findings highlight the importance of hematophagous insects in the epidemiology of pythiosis because these areas are preferred for blood feeding. © 2013 Elsevier Inc. All rights reserved.
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This study investigated the immunotherapeutic potential of the protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride immuno-modulator (P-MAPA) on canine visceral leishmaniasis. Twenty mongrel dogs presenting clinical symptoms compatible with leishmaniasis and diagnosis confirmed by the detection of anti-leishmania antibodies were studied. Ten dogs received 15 doses of the immunomodulator (2.0mg/kg) intramuscularly, and 10 received saline as a placebo. Skin and peripheral blood samples were collected following administration of the immunomodulator. The groups were followed to observe for clinical signals of remission; parasite load in the skin biopsies using real-time PCR, the cytokines IL-2, IL-10 and IFN-γ in the supernatant of peripheral blood mononuclear cells stimulated in vitro with either total promastigote antigen or phytohemagglutinin measured by capture ELISA, and changes in CD4+ and CD8+ T cell subpopulations evaluated by flow cytometry. Comparison between the groups showed that treatment with the immunomodulator promoted improvement in clinical signs and a significant reduction in parasite load in the skin. In peripheral blood mononuclear cell cultures, supernatants showed a decrease in IL-10 levels and an increase in IL-2 and IFN-γ. An increase in CD8+ T cells was observed in peripheral blood. In addition, the in vitro leishmanicidal action of P-MAPA was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and no leishmanicidal activity was detected. These findings suggest that P-MAPA has potential as an immunotherapeutic drug in canine visceral leishmaniasis, since it assists in reestablishing partial immunocompetence of infected dogs. © 2013 Elsevier B.V.
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Type I diabetes is a disease caused by autoimmune destruction of the beta cells in the pancreas that leads to a deficiency in insulin production. The aim of this study was to evaluate the prophylactic potential of a prime-boost strategy involving bacille Calmette-Guérin (BCG) and the pVAXhsp65 vaccine (BCG/DNAhsp65) in diabetes induced by streptozotocin (STZ) in C57BL/6 mice and also in spontaneous type 1 diabetes in non-obese diabetic (NOD) mice. BCG/DNAhsp65 vaccination in NOD mice determined weight gain, protection against hyperglycaemia, decreased islet inflammation, higher levels of cytokine production by the spleen and a reduced number of regulatory T cells in the spleen compared with non-immunized NOD mice. In the STZ model, however, there was no significant difference in the clinical parameters. Although this vaccination strategy did not protect mice in the STZ model, it was very effective in NOD mice. This is the first report demonstrating that a prime-boost strategy could be explored as an immunomodulatory procedure in autoimmune diseases. © 2013 British Society for Immunology.