26 resultados para Rationale

em Repositório Institucional UNESP - Universidade Estadual Paulista "Julio de Mesquita Filho"


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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Rationale: A wealth of evidence supports the involvement of the serotonergic neurons of the median raphe nucleus (MRN) in anxiety. However, it is presently unclear whether serotonergic pathways arising from this nucleus play distinguishing regulatory roles in defensive behaviors that have been associated with specific subtypes of anxiety disorders. Objectives: To evaluate the role of the MRN serotonergic neurons in the regulation of two defensive behaviors, inhibitory avoidance and escape, which have been related, respectively, to generalized anxiety and panic disorders. Methods: Male Wistar rats were submitted to the elevated T-maze test of anxiety after intra-MRN administration of drugs that either non-selectively or selectively change the activity of the serotonergic neurons. Results: Intra-MRN injection of FG 7142 (0.04 and 0.08 nmol) and kainic acid (0.03 and 0.06 nmol), drugs that non-selectively stimulate the MRN serotonergic neurons, facilitated inhibitory avoidance acquisition, but impaired escape performance. Microinjection of muscimol (0.11 and 0.22 nmol), a compound that non-selectively inhibits the activity of the MRN serotonergic neurons, impaired inhibitory avoidance and facilitated escape performance. Both kainic acid and muscimol also changed rat locomotion in the open-field test. Intra-MRN injection of 8-OH-DPAT (0.6-15 nmol) and WAY-100635 (0.18-0.74 nmol), respectively an agonist and an antagonist of somatodendritic 5-HT1A receptors located on serotonergic neurons of the MRN, only affected inhibitory avoidance-while the former inhibited the acquisition of this behavior, the latter facilitated it. Conclusion: MRN serotonergic neurons seem to be selectively involved in the regulation of inhibitory avoidance in the elevated T-maze. This result supports the proposal that 5-HT pathways departing from this nucleus play an important role in anxiety processing, with implications for pathologies such as generalized anxiety disorder.

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Rationale: Mice exhibit antinociception after a single experience in the elevated plus maze (EPM), an animal model of anxiety. Objective: This study investigated the mechanisms involved in this form of anxiety-induced antinociception. Methods: Nociception was evaluated by means of the writhing test in mice confined either to the open or enclosed arms of the EPM. The effects of systemic (naloxone, midazolam and 8-OH-DPAT) or intra-amygdala (8-OH-DPAT. NAN-190 and midazolam) drug infusions were investigated in mice previously treated i.p. with 0.6% acetic acid, an algic stimulus that induces abdominal contortions. The effects of these drugs on conventional measures of anxiety (% entries and % time in open arms) in a standard EPM test were also independently investigated. Results: Open-arm confinement resulted in a high-magnitude antinociception (minimum 85%, maximum 450%) compared with enclosed arm confinement. The opiate antagonist naloxone (1 mg/kg and 10 mg/kg) neither blocked this open arm-induced antinociception (OAIA) nor modified indices of anxiety in EPM. Administration of midazolam (0.5-2 mg/kg, s.c.) increased OAIA and produced antinociception in enclosed confined animals, as well as attenuating anxiety in the EPM. The 5-HT(1A) receptor agonist 8-OH-DPAT (0.05-1 mg/kg, s.c.) had biphasic effects on OAIA, antagonising the response at the lowest dose and intensifying it at the highest dose. In addition, low doses of this agent reduced anxiety in the EPM. Although bilateral injections of 8-OH-DPAT (5.6 nmol/0.4 mu l) or NAN-190 (5.6 nmol and 10 nmol/0.4 mu l) into the amygdala did not alter OAIA, increased anxiety was observed in the EPM. In contrast, intra-amygdala administration of midazolam (10 nmol and 30 nmol/0.4 mu l) blocked both OAIA and anxiety. Conclusions: These results with systemic and intracerebral drug infusion suggest that 5-HT(1A) receptors localised in the amygdala are not involved in the pain inhibitory processes that are recruited during aversive situations. However, activation of these receptors does phasically increase anxiety. Although the intrinsic antinociceptive properties of systemically administered midazolam confounded interpretation of its effects on OAIA, intra-amygdala injections of this compound suggest that benzodiazepine receptors in this brain region modulate both the antinociceptive and behavioural (anxiety) responses to the EPM.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Antineoplastic chemotherapeutic agents may indirectly activate dendritic cells (DCs) by inducing the release of danger signals from dying tumor cells. Whereas the direct cytotoxic or inhibitory effect of conventional chemotherapy on DCs has been reported, modulation of DC function by chemotherapeutic agents in low noncytotoxic concentrations has not yet been investigated. We have tested the effects of different classes of antineoplastic chemotherapeutic agents used in low noncytotoxic concentrations on the Ag-presenting function of DCs. We revealed that paclitaxel, doxorubicin, mitomycin C, and methotrexate up-regulated the ability of DCs to present Ags to Ag-specific T cells. Stimulation of DC function was associated with the up-regulation of expression of Ag-processing machinery components and costimulatory molecules on DCs, as well as increased IL-12p70 expression. However, the ability of DCs treated with paclitaxel, methotrexate, doxorubicin, and vinblastine to increase Ag presentation to Ag-specific T cells was abolished in DCs generated from IL-12 knockout mice, indicating that up-regulation of Ag presentation by DCs is IL-12-dependent and mediated by the autocrine or paracrine mechanisms. At the same time, IL-12 knockout and wild-type DCs demonstrated similar capacity to up-regulate OVA presentation after their pretreatment with low concentrations of mitomycin C and vincristine, suggesting that these agents do not utilize IL-12-mediated pathways in DCs for stimulating Ag presentation. These findings reveal a new mechanism of immunopotentiating activity of chemotherapeutic agents-a direct immunostimulatory effect on DCs (chemomodulation)-and thus provide a strong rationale for further assessment of low-dose chemotherapy given with DC vaccines for cancer treatment. The Journal of Immunology, 2009, 183: 137-144.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Myocardial reperfusion injury is associated with the infiltration of blood-borne polymorphonuclear leukocytes. We have previous described the protection afforded by annexin 1 (ANXA1) in an experimental model of rat myocardial ischemia-reperfusion (IR) injury. We examined the 1) amino acid region of ANXA1 that retained the protective effect in a model of rat heart IR; 2) changes in endogenous ANXA1 in relation to the IR induced damage and after pharmacological modulation; and 3) potential involvement of the formyl peptide receptor (FPR) in the protective action displayed by ANXA1 peptides. Administration of peptide Ac2-26 at 0, 30, and 60 min postreperfusion produced a significant protection against IR injury, and this was associated with reduced myeloperoxidase activity and IL-1 beta levels in the infarcted heart. Western blotting and electron microscopy analyses showed that IR heart had increased ANXA1 expression in the injured tissue, associated mainly with the infiltrated leukocytes. Finally, an antagonist to the FPR receptor selectively inhibited the protective action of peptide ANXA1 and its derived peptides against IR injury. Altogether, these data provide further insight into the protective effect of ANXA1 and its mimetics and a rationale for a clinical use for drugs developed from this line of research.

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Aim. By taking nursing as a human relationships activity, in spite of its strong technical-scientific features, this article reflects on the phenomenological method as one of the ways to develop ail investigation and acquire knowledge of the topic.Rationale. Based on Husserl's phenomenology, which is opposed to the way of doing science based on the laws that regulate the physics and mathematics, the article introduces Merleau Ponty's existential phenomenology as the theoretical foundation for the method it proposes. My existential conceptions-people as historic beings inserted in a world over which they act but which, in its turn, determines them; the human perception as reference for our way of being in the world; the space-time structure of perception-these are the key concepts that have led to the elaboration of ail approach to phenomenological research.Proposal of a methodology. Steps are proposed for such ail approach, namely phenomenological description, reduction and analysis. These lead to the building up of ideographic and nomothetic analyses, thus unveiling and describing general truths about the phenomenon studied. Finally, the possibilities for applying the methodology to nursing research are discussed, illustrated by my research into student nurses' perspectives on working oil an isolation ward.

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The search for new alternatives in order to increase soybeans productivity has been constant objective of researchers and farmers. The crop responses to phosphorus application in the soil are well defined, being this nutrient very important on its development and yield. The leaf fertilization on this crop appears as a new rationale option, mainly when the plant nutrient levels are low. So, this work aimed to study the effect of phosphorus leaf fertilization, applied at different plant stage, including: V5, R1, R4, V5 + R1, V5 + R4, R1 + R4, V5 + R1 + R4, V5 + R1 + R4 + R6 and test plot. The experiment was installed in a soybeans crop, Monarca cultivar, at Palmital Farm, Ijaci county, Minas Gerais state, Brazil, using a totally randomized design, with 9 treatments and 3 replications. The chelate Quimifol P30 in liquid form with 30% of the nutrient soluble in CNA + water in the, with doses of 21. ha(-1), was utilized as phosphorus source, using the applications performed with a constant pressure CO(2)-nebulizer. The different epochs of phosphorous application significantly altered the grains yield, proportioning significant increases, up to 16% for the V5, V5 + R1, V5 + R4, V5 + R1 + R4, V5 + R1 + R4 + R6 epochs, when compared to the test plot, clearly expressing the positive effect of these applications at V5 stage. The plant height, first legume insertion, and lodging index characteristics were not significantly altered by the different epochs evaluated. It was observed significant response for the nutrient leaf amounts only in the case of K and Zn indices, exclusively in the V5 + R4, and in the V5, V5 + R1 and V5 + R1 + R4 + R6 treatments, respectively.

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The Brazilian Ministry of Labour has been attempting to modify the norms used to analyse industrial accidents in the country. For this purpose, in 1994 it tried to make compulsory use of the causal tree approach to accident analysis, an approach developed in France during the 1970s,without having previously determined whether it is suitable for use under the industrial safety conditions that prevail in most Brazilian firms. In addition, apposition from Brazilian employers has blocked the proposed changes to the norms. The present study employed anthropotechnology to analyse experimental application of the causal tree method to work-related accidents in industrial firms in the region of Botucatu, São Paulo. Three work-related accidents were examined in three industrial firms representative of local, national and multinational companies. on the basis of the accidents analysed in this study, the rationale for the use of the causal tree method in Brazil can be summarized for each type of firm as follows:the method is redundant if there is a predominance of the type of risk whose elimination or neutralization requires adoption of conventional industrial safety measures (firm representative of local enterprises); the method is worth while if the company's specific technical risks have already largely been eliminated (firm representative of national enterprises); and the method is particularly appropriate if the firm has a good safety record and the causes of accidents are primarily related to industrial organization and management (multinational enterprise).

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Aspergillus nidulans is a non-pathogenic fungus with well-developed genetics which provides an excellent model system for studying different aspects of drug resistance in filamentous fungi. As a preliminary step to characterizing genes that confer pleiotropic drug resistance in Aspergillus, we isolated cycloheximide-sensitive mutants of A. nidulans, which is normally resistant to this: drug. The rationale for this approach is to identify gents whose products are important for drug resistance by analysing mutations that alter the resistance/sensitivity status of the cell. Fifteen cycloheximide-sensitive (named scy for sensitive to cycloheximide) mutants of A, nidulans were isolated and genetically characterised. Each scy mutant was crossed with the wild-type strain and five of the crosses gave 50% cycloheximide-sensitive progeny suggesting that they carry a single mutation required for cycloheximide sensitivity. We examined ten sep mutants for resistance/sensitivity to other drugs or stress agents with different and/or the same mechanism of action, Sis of these mutants exhibited other altered resistance/sensitivity phenotypes which were linked to the cycloheximide sensitivity, These six mutants were analyzed by pairwise crosses and found to represent six linkage groups, named scyA-F. One of the mutants showed fragmentation of its vacuolar system and, in addition, its growth was osmotic, low-pi-II and oxidative-stress sensitive.

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Bisphosphonates are compounds used in the treatment of various metabolic and malignant bone diseases. The relation between the use of bisphosphonates and ostenonecrosis of the jaws as an adverse effect of the drug has been intensely discussed during the last few years, and up to this moment, there is no consensus concerning an ideal treatment modality for this condition. Nevertheless, there is an agreement among researchers that the standard goal for controlling jaw osteonecrosis is to prevent it. Otherwise, the rationale for a randomized controlled trial is that current treatment has proven to be suboptimal, and no consensus has been reached yet on the best strategies to repair the exposed bone once bone necrosis is developed. This article is focused on reporting a case of moderate osteonecrosis of the upper jaw induced by bisphosphonates and discusses a possible role for surgical debridement associated to platelet-rich plasma, hyperbaric oxygen therapy, and the cessation of the bisphosphonate use in managing this type of lesion. Moreover, the dentist, the oral surgeon, and the oncologist need to work together to reach better outcomes.

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Calendula officinalis L. and S. barbadetiman are used in Brazil for the treatment of a number of aliments. The healing properties of these substances are well known, mainly in domestic or sun burn. In order to establish a pharmacological rationale for the traditional use of these plants as a cicatrizant or antiinflammatory remedy, we used ethanol extracts or gel from stem bark of the S. barbadetiman and inflorescence of the Calendula. We selected four groups of patients; two groups shown varicose ulcer (I, II) and two groups shown skin lesions (III and IV). Groups I and III were treated with Calendula and group II and IV were treated with Calendula plus barbadetiman. The data in this study suggest that the treatment with Calendula or Calendula plus barbadetiman are effective in the process that brings wounds to a close. These findings provide basis to an alternative treatment of varicose ulcer.