976 resultados para ENCODING OATP1B1
Resumo:
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Resumo:
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Resumo:
For any finite commutative ring B with an identity there is a strict inclusion B[X; Z(0)] subset of B[X; Z(0)] subset of B[X; 1/2(2)Z(0)] of commutative semigroup rings. This work is a continuation of Shah et al. (2011) [8], in which we extend the study of Andrade and Palazzo (2005) [7] for cyclic codes through the semigroup ring B[X; 1/2; Z(0)] In this study we developed a construction technique of cyclic codes through a semigroup ring B[X; 1/2(2)Z(0)] instead of a polynomial ring. However in the second phase we independently considered BCH, alternant, Goppa, Srivastava codes through a semigroup ring B[X; 1/2(2)Z(0)]. Hence we improved several results of Shah et al. (2011) [8] and Andrade and Palazzo (2005) [7] in a broader sense. Published by Elsevier Ltd
Resumo:
With the aim of further understanding the structure/function relationships in the membrane-damaging activity of the Lys(49) phospholipase A(2) (Lys(49)-PLA(2)) sub-family, we used PCR (polymerase chain reaction) on total venom gland cDNAs from Bothrops jararacussu with degenerate oligodeoxyribonucleotides encoding the N- and C-termini of myotoxin II, a Lys(49)-PLA(2) from Bothrops asper. A 350-bp cDNA coding for bothropstoxin I (BtxtxI) was amplified. Sequencing of the amplified fragment shows that BtxtxI has a Lys(49), and comparison with the known structure of myotoxin II showed that the amino acids involved in the formation of a novel dimeric structure in this protein were also conserved.
Resumo:
The high incidence of tuberculosis around the world and the inability of BCG to protect certain populations clearly indicate that an improved vaccine against tuberculosis is needed. A single antigen, the mycobacterial heat shock protein hsp65, is sufficient to protect BALB/c mice against challenge infection when administered as DNA vaccine in a three-dose-based schedule. In order to simplify the vaccination schedule, we coencapsulated hsp65-DNA and trehalose dimicolate (TDM) into biodegradable poly(DL-lactide-co-glycolide) (PLGA) microspheres. BALB/c mice immunized with a single dose of DNA-hsp65/TDM-1oaded microspheres produced high levels of IgG2a subtype antibody and high amounts of IFN-gamma in the supernatant of spleen cell cultures. DNA-hsp65/TDM-loaded microspheres were also able to induce high IFN-gamma production in bulk lung cells from challenged mice and confer protection as effective as that attained after three doses of naked DNA administration. This new formulation also allowed a ten-fold reduction in the DNA dose when compared to naked DNA. Thus, this combination of DNA vaccine and adjuvants with immunomodulatory and carrier properties holds the potential for an improved vaccine against tuberculosis.
Resumo:
Granulocyte colony-stimulating factor (G-CSF) acts on precursor hematopoietic cells to control the production and maintenance of neutrophils. Recombinant G-CSF (re-G-CSF)is used clinically to treat patients with neutropenia and has greatly reduced the infection risk associated with bone marrow transplantation. Cyclic hematopoiesis, a stem cell defect characterized by severe recurrent neutropenia, occurs in man and grey collie dogs, and can be treated by administration of re-G-CSF. Availability of the rat G-CSF cDNA would benefit the use of rats as models of gene therapy for the treatment of cyclic hematopoiesis. In preliminary rat experiments, retroviral-mediated expression of canine G-CSF caused neutralizing antibody formation which precluded long-term increases in neutrophil counts. To overcome this problem we cloned the rat G-CSF cDNA from RNA isolated from skin fibroblasts. The rat G-CSF sequence shared a high degree of identity in both the coding and non-coding regions with both the murine G-CSF (85%) and human G-CSF (74%). The signal peptides of murine and human G-CSF both contained 30 amino acids (aa), whereas the deduced signal sequence for rat G-CSF possessed 21 aa. A retrovirus encoding the rat G-CSF cDNA synthesized bioactive G-CSF from transduced vascular smooth muscle cells.
Resumo:
In order to assess a new strategy of DNA vaccine for a more complete understanding of its action in immune response, it is important to determine the in vivo biodistribution fate and antigen expression. In previous studies, our group focused on the prophylactic and therapeutic use of a plasmid DNA encoding the Mycobacterium leprae 65-kDa heat shock protein (Hsp65) and achieved an efficient immune response induction as well as protection against virulent M. tuberculosis challenge. In the present study, we examined in vivo tissue distribution of naked DNA-Hsp65 vaccine, the Hsp65 message, genome integration and methylation status of plasmid DNA. The DNA-Hsp65 was detectable in several tissue types, indicating that DNA-Hsp65 disseminates widely throughout the body. The biodistribution was dose-dependent. In contrast, RT-PCR detected the Hsp65 message for at least 15 days in muscle or liver tissue from immunized mice. We also analyzed the methylation status and integration of the injected plasmid DNA into the host cellular genome. The bacterial methylation pattern persisted for at least 6 months, indicating that the plasmid DNA-Hsp65 does not replicate in mammalian tissue, and Southern blot analysis showed that plasmid DNA was not integrated. These results have important implications for the use of DNA-Hsp65 vaccine in a clinical setting and open new perspectives for DNA vaccines and new considerations about the inoculation site and delivery system. © 2006 Coelho-Castelo et al; licensee BioMed Central Ltd.
Resumo:
This paper presents the overall methodology that has been used to encode both the Brazilian Portuguese WordNet (WordNet.Br) standard language-independent conceptual-semantic relations (hyponymy, co-hyponymy, meronymy, cause, and entailment) and the so-called cross-lingual conceptual-semantic relations between different wordnets. Accordingly, after contextualizing the project and outlining the current lexical database structure and statistics, it describes the WordNet.Br editing GUI that was designed to aid the linguist in carrying out the tasks of building synsets, selecting sample sentences from corpora, writing synset concept glosses, and encoding both language-independent conceptual-semantic relations and cross-lingual conceptual-semantic relations between WordNet.Br and Princeton WordNet © Springer-Verlag Berlin Heidelberg 2006.
Resumo:
Background: Protein-calorie malnutrition (PCM) is the most common type of malnutrition. PCM leads to immunodeficiency and consequent increased susceptibility to infectious agents. In addition, responses to prophylactic vaccines depend on nutritional status. This study aims to evaluate the ability of undernourished mice to mount an immune response to a genetic vaccine (pVAXhsp65) against tuberculosis, containing the gene coding for the heat shock protein 65 from mycobacteria. Methods: Young adult female BALB/c mice were fed ad libitum or with 80% of the amount of food consumed by a normal diet group. We initially characterized a mice model of dietary restriction by determining body and spleen weights, hematological parameters and histopathological changes in lymphoid organs. The ability of splenic cells to produce IFN-gamma and IL-4 upon in vitro stimulation with LPS or S. aureus and the serum titer of specific IgG1 and IgG2a anti-hsp65 antibodies after intramuscular immunization with pVAXhsp65 was then tested. Results: Dietary restriction significantly decreased body and spleen weights and also the total lymphocyte count in blood. This restriction also determined a striking atrophy in lymphoid organs as spleen, thymus and lymphoid tissue associated with the small intestine. Specific antibodies were not detected in mice submitted to dietary restriction whereas the well nourished animals produced significant levels of both, IgG1 and IgG2a anti-hsp65. Conclusion: 20% restriction in food intake deeply compromised humoral immunity induced by a genetic vaccine, alerting, therefore, for the relevance of the nutritional condition in vaccination programs based on these kinds of constructs. © 2009 Ishikawa et al; licensee BioMed Central Ltd.
Resumo:
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Resumo:
Let B[X; S] be a monoid ring with any fixed finite unitary commutative ring B and is the monoid S such that b = a + 1, where a is any positive integer. In this paper we constructed cyclic codes, BCH codes, alternant codes, Goppa codes, Srivastava codes through monoid ring . For a = 1, almost all the results contained in [16] stands as a very particular case of this study.
Resumo:
A atorvastatina, amplamente utilizada no tratamento de dislipidemias, é fármaco inibidor da enzima 3-hidroxi-3-metilglutaril coenzima A redutase (HMG-CoA) redutase que atua na etapa limitante da síntese do colesterol nas células hepáticas. O transporte hepatocelular da atorvastatina é mediado principalmente pelo polipeptídeo transportador de ânions orgânicos (OATP) 1B1, o qual é altamente polimórfico geneticamente e está sujeito a interação com outros fármacos usados na clínica. O presente estudo teve como objetivo revisar a literatura científica baseada em estudos clínicos, in vitro e experimentais a fim de avaliar o impacto de polimorfismos genéticos de OATP1B1 na disposição cinética, eficácia e toxicidade da atorvastatina. Os estudos clínicos demonstram que o polimorfismo c.521T>C, presente nos alelos SLCO1B1 *5 e *15, resulta em alteração funcional da atividade transportadora, sendo que indivíduos homozigotos para o alelo raro C, apresentam maiores concentrações plasmáticas de atorvastatina e seus metabólitos ativos 2-hidroxiatorvastatina e 4- hidroxiatorvastatina. Entretanto, o aumento na concentração plasmática da atorvastatina e seus metabólitos ativos em indivíduos c.521 CC parece não ser acompanhado de redução na concentração dos mesmos no sítio alvo, tendo em vista que não foram encontradas diferenças significativas na redução da LDL-C ou colesterol total quando comparados aos indivíduos homozigotos para o alelo selvagem. O alelo SLCO1B1*15 mostrou-se significativamente associado a miopatia induzida pela atorvastatina, apesar do pequeno número de pacientes investigados. Estudos in vitro em células expressando OATP1B1 são necessários a fim de investigar o impacto do polimorfismo c.521T>C na concentração de atorvastatina nos hepatócitos. Sugere-se ainda que estudos clínicos sejam conduzidos a fim de avaliar se a redução da dose de...