26 resultados para ESTROGEN POSITIVE FEEDBACK

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


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The inappropriate use of antimicrobials in hospitals presents a negative impact on patient outcome and is associated with the emergence and spread of multidrug-resistant microorganisms. Antimicrobial stewardship programs (ASPs) have been instituted in order to improve the quality of prescriptions in hospitals. In this setting, the identification of patterns of inappropriate antimicrobial prescription is a valuable tool that allows ASPs to identify priorities for directing educative/restrictive policies. With this purpose, a study was conducted in the Bauru State Hospital, a teaching hospital with 285 beds affiliated to the Botucatu Medical School, São Paulo State University. The hospital maintains an active ASP since it was opened, in 2002. We selected 25% of the requests for parenteral antimicrobials (RPAs) from 2005 for analysis. Prescriptions for prophylactic purposes were excluded. All other RPAs were classified according to a modified Kunin and Jones categories. Univariate and multivariable analyses were performed to identify predictors of general inappropriateness and of specific prescription errors. Prescriptions classified as "appropriate'' or "probably appropriate" were selected as controls in all stages of the study. Among 963 RPAs included in our study, 34.6% were inappropriate. General predictors of inappropriateness were: prescription on weekends/holidays (OR = 1.67, 95% CI = 1.20-2.28, p = 0.002), patient from intensive care unit (OR = 1.57, 95% CI = 1.11-2.23, p = 0.01), peritoneal (OR = 2.15, 95% CI = 1.27-3.65, p = 0.004) or urinary tract infection (OR = 1.89, 95% CI = 1.25-2.87, p = 0.002), combined therapy with two or more antimicrobials (OR = 1.72, 95% CI = 1.15-2.57, p = 0.008) and prescriptions including penicillin (OR = 2.12, 95% CI = 1.39-3.25, p = 0.001) or first-generation cephalosporins (OR = 1.74, 95% CI = 1.01-3.00, p = 0.048). Previous consultation with an infectious diseases (ID) specialist had a protective effect against inappropriate prescription (OR = 0.34, 95% CI = 0.24-0.50, p < 0.001). Factors independently associated with specific prescription errors varied. However, consultation with an ID specialist was protective against both unnecessary antimicrobial use (OR = 0.04, 95% CI = 0.01-0.26, p = 0.001) and requests for agents with insufficient spectrum (OR = 0.14, 95% CI = 0.03-0.30, p = 0.01). In conclusion, the analysis of factors predictive of inappropriateness in antimicrobial prescription allowed us to identify issues requiring intervention. Also, it provided a positive feedback of the ASP efficacy, demonstrating the importance of previous consultation with an ID specialist to assure the quality of antimicrobial prescriptions.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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We studied the statistical distribution of candidate's performance which is measured through their marks in university entrance examination (Vestibular) of UNESP (Universidade Estadual Paulista) for years 1998, 1999, and 2000. All students are divided in three groups: Physical, Biological and Humanities. We paid special attention to the examination of Portuguese language which is common for all and examinations for the particular area. We observed long ubiquitous power law tails in Physical and Biological sciences. This indicate the presence of strong positive feedback in sciences. We are able to explain completely these statistical distributions through Gradually Truncated Power law distributions which we developed recently to explain statistical behavior of financial market. The statistical distribution in case of Portuguese language and humanities is close to normal distribution. We discuss the possible reason for this peculiar behavior.

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Pós-graduação em Física - IGCE

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Pós-graduação em Genética - IBILCE

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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

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The mechanisms underlying improvement of neuromuscular transmission deficits by glucocorticoids are still a matter of debate despite these compounds have been used for decades in the treatment of autoimmune myasthenic syndromes. Besides their immunosuppressive action, corticosteroids may directly facilitate transmitter release during high-frequency motor nerve activity. This effect coincides with the predominant adenosine A(2A) receptor tonus, which coordinates the interplay with other receptors (e.g. muscarinic) on motor nerve endings to sustain acetylcholine (ACh) release that is required to overcome tetanic neuromuscular depression in myasthenics. Using myographic recordings, measurements of evoked [H-3]ACh release and real-time video microscopy with the FM4-64 fluorescent dye, results show that tonic activation of facilitatory A(2A) receptors by endogenous adenosine accumulated during 50 Hz bursts delivered to the rat phrenic nerve is essential for methylprednisolone (03 mM)-induced transmitter release facilitation, because its effect was prevented by the A(2A) receptor antagonist, ZM 241385 (10 nM). Concurrent activation of the positive feedback loop operated by pirenzepine-sensitive muscarinic M-1 autoreceptors may also play a role, whereas the corticosteroid action is restrained by the activation of co-expressed inhibitory M-2 and Al receptors blocked by methoctramine (0.1 mu M) and DPCPX (2.5 nM), respectively. Inhibition of FM4-64 loading (endocytosis) by methylprednisolone following a brief tetanic stimulus (50 Hz for 5 s) suggests that it may negatively modulate synaptic vesicle turnover, thus increasing the release probability of newly recycled vesicles. Interestingly, bulk endocytosis was rehabilitated when methylprednisolone was co-applied with ZM241385. Data suggest that amplification of neuromuscular transmission by methylprednisolone may involve activation of presynaptic facilitatory adenosine A(2A) receptors by endogenous adenosine leading to synaptic vesicle redistribution. (C) 2014 Elsevier Ltd. All rights reserved.

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

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In the early vertebrate embryo, cardiac progenitor/precursor cells (CPs) give rise to cardiac structures. Better understanding their biological character is critical to understand the heart development and to apply CPs for the clinical arena. However, our knowledge remains incomplete. With the use of single-cell expression profiling, we have now revealed rapid and dynamic changes in gene expression profiles of the embryonic CPs during the early phase after their segregation from the cardiac mesoderm. Progressively, the nascent mesodermal gene Mesp1 terminated, and Nkx2-5+/Tbx5+ population rapidly replaced the Tbx5low+ population as the expression of the cardiac genes Tbx5 and Nkx2-5 increased. At the Early Headfold stage, Tbx5-expressing CPs gradually showed a unique molecular signature with signs of cardiomyocyte differentiation. Lineage-tracing revealed a developmentally distinct characteristic of this population. They underwent progressive differentiation only towards the cardiomyocyte lineage corresponding to the first heart field rather than being maintained as a progenitor pool. More importantly, Tbx5 likely plays an important role in a transcriptional network to regulate the distinct character of the FHF via a positive feedback loop to activate the robust expression of Tbx5 in CPs. These data expands our knowledge on the behavior of CPs during the early phase of cardiac development, subsequently providing a platform for further study.

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Pós-graduação em Engenharia Elétrica - FEIS

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

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Feasibility of nonlinear and adaptive control methodologies in multivariable linear time-invariant systems with state-space realization (A, B, C) is apparently limited by the standard strictly positive realness conditions that imply that the product CB must be positive definite symmetric. This paper expands the applicability of the strictly positive realness conditions used for the proofs of stability of adaptive control or control with uncertainty by showing that the not necessarily symmetric CB is only required to have a diagonal Jordan form and positive eigenvalues. The paper also shows that under the new condition any minimum-phase systems can be made strictly positive real via constant output feedback. The paper illustrates the usefulness of these extended properties with an adaptive control example. (C) 2006 Elsevier Ltd. All rights reserved.

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To elucidate the molecular profile of hormonal steroid receptor status, we analyzed ER-alpha, ER-beta, and PGR mRNA and protein expression in 80 breast carcinomas using reverse transcriptase polymerase chain reaction (RT-PCR), quantitative RT-PCR, and immunohistochemical analysis. Qualitative analysis revealed positive expression of ER-alpha, ER-beta, and PGR mRNA in 48%, 59%, and 48% of the breast carcinomas, respectively. ER-alpha, ER-beta, and PGR transcript overexpression was observed in 51%, 0%, and 12% of the cases, respectively, whereas moderate or strong protein expression was detected in 68%, 78%, and 49% of the cases, respectively. Tumor grade was negatively correlated with transcript and protein levels of ER-alpha (P = .0169 and P = .0006, respectively) and PGR (P = .0034 and P = .0005, respectively). Similarly, proliferative index Ki-67 was negatively associated with transcript and protein levels of ER-alpha (P = .0006 and P < .0001, respectively) and PGR (P = .0258 and P =. 0005, respectively). These findings suggest that ER-alpha and PGR expression are associated with well-differentiated breast tumors and less directly related to cell proliferation. A significant statistical difference was observed between lymph node status and ER-beta protein expression (P = .0208). In ER-alpha-negative tumors, we detected a correlation between ER-beta protein expression and high levels of Ki-67. These data suggest that ER-beta could be a prognostic marker in human breast cancer. (C) 2008 Elsevier B.V. All rights reserved.

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Bone is a mineralized tissue that is under the influence of several systemic, local and environmental factors. Among systemic factors, estrogen is a hormone well known for its inhibitory function on bone resorption. As alveolar bone of young rats undergoes continuous and intense remodeling to accommodate the growing and erupting tooth, it is a suitable in vivo model for using to study the possible action of estrogen on bone. Thus, in an attempt to investigate the possibility that estrogen may induce the death of osteoclasts, we examined the alveolar bone of estrogen-treated rats.Fifteen, 22-d-old female rats were divided into estrogen, sham and control groups. The estrogen group received estrogen and the sham group received corn oil used as the dilution vehicle. After 8 d, fragments containing alveolar bone were removed and processed for light microscopy and transmission electron microscopy. Sections were stained with hematoxylin and eosin and tartrate-resistant acid phosphatase (TRAP)-an osteoclast marker. Quantitative analysis of the number of TRAP-positive osteoclasts per mm of bone surface was carried out. For detecting apoptosis, sections were analyzed by the Terminal deoxynucleotidyl transferase-mediated dUTP Nick-End Labeling (TUNEL) method; TUNEL/TRAP combined methods were also used.The number of TRAP-positive osteoclasts per mm of bone surface was significantly reduced in the estrogen group compared with the sham and control groups. TRAP-positive osteoclasts exhibiting TUNEL-positive nuclei were observed only in the estrogen group. In addition, in the estrogen group the ultrastructural images revealed shrunken osteoclasts exhibiting nuclei with conspicuous and tortuous masses of condensed chromatin, typical of apoptosis.Our results reinforce the idea that estrogen inhibits bone resorption by promoting a reduction in the number of osteoclasts, thus indicating that this reduction may be, at least in part, a consequence of osteoclast apoptosis.