897 resultados para TARGETED DISRUPTION
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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The aim of this study was to evaluate two root canal filling techniques used in teeth that had their apical foramen disrupted and compare the apical infiltration with an ideal clinical situation. Twenty-seven freshly extracted single-rooted teeth were selected and radiographed to confirm the existence of a single and straight root canal. The crowns were removed at a mean distance of 11 mm from the apex. The teeth had the root canals instrumented and were randomly assigned to 3 groups (n=9): ND group-root canals were filled using the lateral compaction technique and no disruption was performed; DRF group-the apical constriction was disrupted by advancing a #40 K-file 1 mm beyond the original working length, the canals were reinstrumented to create an apical ledge at 1 mm from the apical foramen and were obturated with a master gutta-percha cone with same size as the last file used for reinstrumentation; DF group - the teeth had the apical constriction disrupted and the canals were obturated with a master gutta-percha cone that fit at 1 mm from the apex. The teeth were submitted to dye leakage test with Rhodamine B for 7 days, using vaccum on the initial 5 min. The teeth were sectioned longitudinally and the leakage was measured in a linear fashion from apex to crown. There was no statistically significant difference (p>0.05) between the groups that had the apical foramen disrupted (DF, DRF), but significant difference was found between the disrupted groups and the non-disrupted one (p<0.01). In conclusion, none of the evaluated techniques was able to prevent apical infiltration, so working length so the working length determination has to be established and maintained carefully.
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Venom phospholipase A(2)s (PLA(2)s) display a wide spectrum of pharmacological activities and, based on the wealth of biochemical and structural data currently available for PLA(2)S, mechanistic models can now be inferred to account for some of these activities. A structural model is presented for the role played by the distribution of surface electrostatic potential in the ability of myotoxic D49/K49 PLA(2)s to disrupt multilamellar vesicles containing negatively charged natural and non-hydrolyzable phospholipids. Structural evidence is provided for the ability of K49 PLA(2)s to bind phospholipid analogues and for the existence of catalytic activity in K49 PLA(2)s. The importance of the existence of catalytic activity of D49 and K49 PLA(2)s in myotoxicity is presented. (C) 2003 Elsevier Ltd. All rights reserved.
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This experiment was developed in order to evaluation the efficiency of pheromone to control the pink bollworm and the total time of its release in cotton field. The experiment was installed in field conditions, in Chapadao do Sul/SP/Brazil, from January to April, 1998. The treatments consisted of 2 areas, being one of 30ha, where it was applied the pheromone and another of 10ha that was chosen as control area and did not receive pheromone. In the treated area, the laboratory synthesized sex pheromone (PB-Rope) was used thought of dispensers that allowed the slow and gradual release of the active substance. A total of 250 dispenser per hectare were evenly hand distributed in the area. The dispensers were wrapped around the plants. Both areas (treated area and untreated area) were monitored by delta trap. For evaluation of the boll damage, the treatment area was divided into 4 sub-areas. Twenty five green bolls were collected at random from each sub-area at 48 and 65 days after pheromone treatment. Bolls were cracked open by hand, and number of the bolls with symptoms of pink bollworm attacks was recorded. For evaluation of the productivity four areas were demarcated in each treatment, where all fibers and seeds harvested were weighted. Release rate of pheromone from dispenser was evaluated through of the weigh of the dispensers. Were marked and weighed in analytic scale, 20 dispensers contend the pheromone, being placed 10 dispensers under the cotton plants in treated area and other 10 dispensers in an open area. To every 15 days the dispensers were retired and weighed in analytic scale and soon after put back in the field in the same places. The results showed that only one application of mating disrupt pheromone, used in a dosage of 250 dispenser/ha, reached 80% of control for pink bollworm. the release period of pheromone from dispenser, after the application, was 120 days.
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Mucopolysaccharidoses (MPS) are rare lysosomal disorders caused by the deficiency of specific lysosomal enzymes responsible for glycosaminoglycan (GAG) degradation. Enzyme Replacement Therapy (ERT) has been shown to reduce accumulation and urinary excretion of GAG, and to improve some of the patients' clinical signs. We studied biochemical and molecular characteristics of nine MPS patients (two MPS I, four MPS II and three MPS VI) undergoing ERT in northern Brazil. The responsiveness of ERT was evaluated through urinary GAG excretion measurements. Patients were screened for eight common MPS mutations, using PCR, restriction enzyme tests and direct sequencing. Two MPS I patients had the previously reported mutation p.P533R. In the MPS II patients, mutation analysis identified the mutation p.R468W, and in the MPS VI patients, polymorphisms p.V358M and p.V376M were also found. After 48 weeks of ERT, biochemical analysis showed a significantly decreased total urinary GAG excretion in patients with MPS I (p < 0.01) and MPS VI (p < 0.01). Our findings demonstrate the effect of ERT on urinary GAG excretion and suggest the adoption of a screening strategy for genotyping MPS patients living far from the main reference centers.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Mutations in the coding region of telomerase complex genes can result in accelerated telomere attrition and human disease. Manifestations of telomere disease include the bone marrow failure syndromes dyskeratosis congenita and aplastic anemia, acute myeloid leukemia, liver cirrhosis, and pulmonary fibrosis. Here, we describe a mutation in the CCAAT box (GCAAT) of the TERC gene promoter in a family in which multiple members had typical features of telomeropathy. The genetic alteration in this critical regulatory sequence resulted in reduced reporter gene activity and absent binding of transcription factor NF-Y, likely responsible for reduced TERC levels, decreased telomerase activity, and short telomeres. This is the first description of a pathogenic mutation in the highly con-served CCAAT box and the first instance of a mutation in the promoter region of TERC producing a telomeropathy. We propose that current mutation-screening strategies should include gene promoter regions for the diagnosis of telomere diseases. This clinical trial was registered at www.clinicaltrials.gov as #NCT00071045. (Blood. 2012;119(13):3060-3063)
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The search for reconsolidation blockers may uncover clinically relevant drugs for disrupting memories of significant stressful life experiences, such as those underlying the posttraumatic stress disorder. Considering the safety of systemically administered cannabidiol (CBD), the major non-psychotomimetic component of Cannabis sativa, to animals and humans, the present study sought to investigate whether and how this phytocannabinoid (3-30 mg/kg intraperitoneally; i.p.) could mitigate an established memory, by blockade of its reconsolidation, evaluated in a contextual fear-conditioning paradigm in rats. We report that CBD is able to disrupt 1- and 7-days-old memories when administered immediately, but not 6 h, after their retrieval for 3 min, with the dose of 10 mg/kg being the most effective. This effect persists in either case for at least 1 week, but is prevented when memory reactivation was omitted, or when the cannabinoid type-1 receptors were antagonized selectively with AM251 (1.0 mg/kg). Pretreatment with the serotonin type-1A receptor antagonist WAY100635, however, failed to block CBD effects. These results highlight that recent and older fear memories are equally vulnerable to disruption induced by CBD through reconsolidation blockade, with a consequent long-lasting relief in contextual fear-induced freezing. Importantly, this CBD effect is dependent on memory reactivation, restricted to time window of <6h, and is possibly dependent on cannabinoid type-1 receptor-mediated signaling mechanisms. We also observed that the fear memories disrupted by CBD treatment do not show reinstatement or spontaneous recovery over 22 days. These findings support the view that reconsolidation blockade, rather than facilitated extinction, accounts for the aforementioned CBD results in our experimental conditions. Neuropsychopharmacology (2012) 37, 2132-2142; doi:10.1038/npp.2012.63; published online 2 May 2012
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Chronic Chagas cardiomyopathy evolves over a long period of time after initial infection by Trypanosoma cruzi. Similarly, a cardiomyopathy appears later in life in muscular dystrophies. This study tested the hypothesis that dystrophin levels are decreased in the early stage of T cruzi-infected mice that precedes the later development of a cardiomyopathy. CD1 mice were infected with T cruzi (Brazil strain), killed at 30 and 100 days post infection (dpi), and the intensity of inflammation, percentage of interstitial fibrosis, and dystrophin levels evaluated. Echocardiography and magnetic resonance imaging data were evaluated from 15 to 100 dpi. At 30 dpi an intense acute myocarditis with ruptured or intact intracellular parasite nests was observed. At 100 dpi a mild chronic fibrosing myocarditis was detected without parasites in the myocardium. Dystrophin was focally reduced or completely lost in cardiomyocytes at 30 dpi, with the reduction maintained up to 100 dpi. Concurrently, ejection fraction was reduced and the right ventricle was dilated. These findings support the hypothesis that the initial parasitic infection-induced myocardial dystrophin reduction/loss, maintained over time, might be essential to the late development of a cardiomyopathy in mice. (C) 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.