Early pregnancy factor suppresses the infiltration of lymphocytes and macrophages in the spinal cord of rats during experimental autoimmune encephalomyelitis but has no effect on apoptosis

Early pregnancy factor (EPF) is a secreted protein with immunosuppressive and growth factor properties that has been shown to suppress acute experimental autoimmune encephalomyelitis (EAE) induced with myelin basic protein (MBP) in Lewis rats. EAE is associated with infiltration of the central nervous system (CNS) with inflammatory cells. Spontaneous recovery involves the loss of T lymphocytes from the CNS and the selective apoptosis of Vbeta8.2(+) cells. In the present study, T cell, macrophage (CD11b/c(+)) and B cell (CD45RA(+)) populations in spinal cord and popliteal lymph nodes (LN) of Lewis rats with EAE were quantitated and apoptosis was studied. Rats were treated with EPF or vehicle. Following treatment on day 14 after inoculation with MBP, neither 1 x 100 mug nor 2 x 100 mug doses of EPF affected the total number of cells infiltrating the spinal cord on day 15, although the higher dose caused a decrease in the number of CD5(+) and CD11b/c(+) cells. Treatment with 2 x 100 mug/day from days 10 to 14 decreased the total number of infiltrating cells, and the numbers of CD5(+), CD11b/c(+) and CD45RA(+) cells. Apoptosis was unaffected. No alteration on the number or type of inflammatory cells in the popliteal LN was observed after treatment on days 10-14. However, treatment with EPF from days 0 to 11 increased the total number of T and B cells and CD5(+) T cells found on day 12 in the LN. Similarly, there was an increase in the frequency of MBP-reactive cells in the LN as determined by limiting dilution analysis. These results suggest that EPF treatment reduces the numbers of lymphocytes and macrophages in the CNS, possibly through an effect on cell trafficking. (C) 2003 Elsevier B.V. All rights reserved.

Patients with early diabetic heart disease demonstrate a normal myocardial response to dobutamine

OBJECTIVES We sought to use quantitative markers of the regional left ventricular (LV) response to stress to infer whether diabetic cardiomyopathy is associated with ischemia. BACKGROUND Diabetic cardiomyopathy has been identified in clinical and experimental studies, but its cause remains unclear. METHODS We studied 41 diabetic patients with normal resting LV function and a normal dobutamine echo and 41 control subjects with a low probability of coronary disease. Peak myocardial systolic velocity (Sm) and early diastolic velocity (Em) in each segment were averaged, and mean Sm and Em were compared between diabetic patients and controls and among different stages of dobutamine stress. RESULTS Both Sm and Em progressively increased from rest to peak dobutamine stress. In the diabetic group, Sm was significantly lower than in control subjects at baseline (4.2 +/- 0.9 cm/s vs. 4.7 +/- 0.9 cm/s, p = 0.012). However, Sin at a low dose (6.0 +/- 1.3), before peak (8.4 +/- 1.8), and at peak stress (8.9 +/- 1.8) in diabetic patients was not significantly different from that of controls (6.3 +/- 1.4, 8.9 +/- 1.6, and 9.6 +/- 2.1 cm/s, respectively). The Em (cm/s) in the diabetic group (rest: 4.2 +/- 1.2; low dose: 5.0 +/- 1.4; pre-peak: 5.3 +/- 1.1; peak: 5.9 +/- 1.5) was significantly lower than that of controls (rest: 5.8 +/- 1.5; low dose: 6.6 +/- 1.5; pre-peak: 6.9 +/- 1.3; peak: 7.3 +/- 1.7; all p < 0.001). However, the absolute and relative increases in Sm or Em from rest to peak stress were similar in diabetic and control groups. CONCLUSIONS Subtle LV dysfunction is present in diabetic patients without overt cardiac disease. The normal response to stress suggests that ischemia due to small-vessel disease may not be important in early diabetic heart muscle disease. (C) 2003 by the American College of Cardiology Foundation.

Ventricular dysfunction in early diabetic heart disease: detection, mechanisms and significance

The detection of preclinical heart disease is a new direction in diabetes care. This comment describes the study by Vinereanu and co-workers in this issue of Clinical Science in which tissue Doppler echocardiography has been employed to demonstrate subtle systolic and diastolic dysfunction in Type 11 diabetic patients who had normal global systolic function and were free of coronary artery disease. The aetiology of early ventricular dysfunction in diabetes relates to complex intramyocardial and extramyocardial mechanisms. The initiating event may be due to insulin resistance, and involves abnormal myocardial substrate utilization and uncoupling of mitochondrial oxidative phosphorylation. Dysglycaemia plays an important role via the effects of oxidative stress, protein kinase C activation and advanced glycosylation end-products on inflammatory signalling, collagen metabolism and fibrosis. Extramyocardial mechanisms involve peripheral endothelial dysfunction, arterial stiffening and autonomic neuropathy. The clinical significance of the ventricular abnormalities described is unknown. Confirmation of their prognostic importance for cardiac disease in diabetes would justify routine screening for presymptomatic ventricular dysfunction, as well as clinical trials of novel agents for correcting causal mechanisms. These considerations could also have implications for patients with obesity and the metabolic syndrome.

Learning about life and death in early childhood

Inagaki and Hatano (2002) have argued that young children initially understand biological phenomena in terms of vitalism, a mode of construal in which life or life-force is the central causal-explanatory concept. This study investigated the development of vitalistic reasoning in young children's concepts of life, the human body and death. Sixty preschool children between the ages of 3 years, 7 months and 5 years, 11 months participated. All children were initially given structured interviews to assess their knowledge of (1) human body function and (2) death. From this sample 40 children in the Training group were taught about the human body and how it functions to maintain life. The Control group (n = 20) received no training. All 60 children were subsequently reassessed on their knowledge of human body function and death. Results from the initial interviews indicated that young children who spontaneously appealed to vitalistic concepts in reasoning about human body functioning were also more sophisticated in their understanding of death. Results from the posttraining interviews showed that children readily learned to adopt a vitalistic approach to human body functioning, and that this learning coincided with significant development in their understanding of human body function, and of death. The overall pattern of results supports the claim that the acquisition of a vitalistic causal-explanatory framework serves to structure children's concepts and facilitates learning in the domain of biology. (C) 2003 Elsevier Science (USA). All rights reserved.

Potential for early involvement of CYP isoforms in aspects of human cadmium toxicity

This paper investigates the possible link between non-workplace cadmium (Cd) exposure, cytochrome P450 expression and hypertension. We present results of our investigation into the relationships between liver and kidney Cd burdens and the abundance of the CYP isoform 4A11. Our data show associations between non-workplace Cd exposure and changes in the abundance of hepatic and renal cortical CYP4A11. In liver the levels of immunochemically detectable CYP4A11 were positively correlated with tissue Cd content while in contrast CYP4A11 abundance was inversely correlated with kidney Cd burden. These differences are most likely related to the different Cd burden of the tissues. These observations suggest the potential for involvement of Cd as a mediator of CYP4A11 expression in kidney cortex and indicate that elevations in kidney Cd content may be involved in hypertension via alteration of the expression of this particular isoform. Potential mechanisms by which Cd may alter CYP4A11 expression are discussed briefly. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

A protective effect of early pregnancy factor on experimental autoimmune encephalomyelitis induced in Lewis rats by inoculation with myelin basic protein

Experimental antoimmune encephalomyelitis (EAE) is an organ-specific autoimmune disease characterised by inflammation and demyelination of the central nervous system and is the best available animal model of multiple sclerosis (MS). Since previous studies have shown that EAE is less severe or is delayed in onset during pregnancy and that administration of the pregnancy hormone early pregnancy factor (EPF) down-regulates EAE, experiments in the present study were designed to explore further the role of EPF in EAE. By using the rosette inhibition test, the standard bioassay for EPF and, by semi-quantitative RT-PCR techniques, we have now shown that inflammatory cells from the spinal cord of rats with EAE can produce and secrete EPF, with production being greatest during recovery from disease. Administration of EPF to rats with EAE resulted in a significant increase in the expression of IL-4 and IL-10 mRNA and a significant decrease in IFN-gamma mRNA expression in spinal cord inflammatory cells. Encephalitogenic MBP-specific T cell lines were prepared from popliteal lymph nodes of rats with EAE. Proliferation assays using these cells demonstrated the ability of exogenous EPF to down-regulate the responses of T lymphocytes to MBP. (C) 2003 Elsevier B.V. All rights reserved.

Improving the public management career: report for the ministry of planning, budgeting e management, federal government of Brazil

This report sets out the findings and recommendations of a review of the Public Management Career (EPPGG) undertaken between 5 and 9 January 2009. The purpose of the review was to clarify EPPGG???s role, functions and profile, and to develop proposals for improving its effectiveness and management, taking account of the context within which such improvements would have to be implemented. Specific objectives were to examine a number of human resources management (HRM) aspects of the career in the light of international practice, including recruitment; initial education; professional development; performance evaluation; deployment; mobility and networking.

Nova gest??o p??blica e motiva????o no servi??o p??blico: a carreira de EPPGG como alternativa para as disfun????es burocr??ticas

Este artigo visa compreender at?? que ponto as pr??ticas gerenciais incorporam as dimens??es da satisfa????o e motiva????o no trabalho de servidores p??blicos na atualidade. Aborda os modelos de administra????o burocr??tica e gerencial, exp??e as disfun????es do modelo ideal da burocracia weberiana, apresenta a motiva????o para o trabalho e suas implica????es, e evidencia a carreira de Especialista em Pol??ticas P??blicas e Gest??o Governamental (EPPGG) no intuito de apresentar uma alternativa poss??vel de proporcionar satisfa????o e motiva????o no trabalho, por meio do enriquecimento do cargo. A metodologia consta de uma pesquisa qualitativa, na qual se fez uso de entrevistas semiestruturadas aplicadas junto a tr??s EPPGG. Utilizou-se da an??lise de conte??do com uso da t??cnica de categoriza????o para a an??lise os dados. Os resultados demonstraram a satisfa????o e motiva????o dos gestores, a preval??ncia da administra????o burocr??tica com fortes ind??cios da administra????o gerencial e aus??ncia de disfun????es burocr??ticas. Evidenciaram que o modelo da nova gest??o p??blica, uma vez implantado conforme descrito na teoria, pode combater disfun????es burocr??ticas e contribuir para a satisfa????o e motiva????o dos servidores p??blicos. Destaca-se a relev??ncia de estudos posteriores, visto que foram apontadas diversidades de condi????es de trabalho de ??rg??o para ??rg??o e dificuldades enfrentadas no in??cio da carreira.

Ventricular performance and Na+-K+ ATPase activity are reduced early and late after myocardial infarction in rats

Myocardial infarction leads to compensatory ventricular remodeling. Disturbances in myocardial contractility depend on the active transport of Ca2+ and Na+, which are regulated by Na+-K+ ATPase. Inappropriate regulation of Na+-K+ ATPase activity leads to excessive loss of K+ and gain of Na+ by the cell. We determined the participation of Na+-K+ ATPase in ventricular performance early and late after myocardial infarction. Wistar rats (8-10 per group) underwent left coronary artery ligation (infarcted, Inf) or sham-operation (Sham). Ventricular performance was measured at 3 and 30 days after surgery using the Langendorff technique. Left ventricular systolic pressure was obtained under different ventricular diastolic pressures and increased extracellular Ca2+ concentrations (Ca2+e) and after low and high ouabain concentrations. The baseline coronary perfusion pressure increased 3 days after myocardial infarction and normalized by 30 days (Sham 3 = 88 ± 6; Inf 3 = 130 ± 9; Inf 30 = 92 ± 7 mmHg; P < 0.05). The inotropic response to Ca2+e and ouabain was reduced at 3 and 30 days after myocardial infarction (Ca2+ = 1.25 mM; Sham 3 = 70 ± 3; Inf 3 = 45 ± 2; Inf 30 = 29 ± 3 mmHg; P < 0.05), while the Frank-Starling mechanism was preserved. At 3 and 30 days after myocardial infarction, ventricular Na+-K+ ATPase activity and contractility were reduced. This Na+-K+ ATPase hypoactivity may modify the Na+, K+ and Ca2+ transport across the sarcolemma resulting in ventricular dysfunction.

Sentidos da formação docente para a profissionalização - Na voz do professor do campo

O trabalho discute os sentidos da formação docente na profissionalização de professores do campo. Nasce do desassossego que interroga a prática da formação continuada, sobretudo, a especialização em educação do campo e os sentidos que são produzidos pelos sujeitos em interface com o trabalho docente nas experiências da Escola Família Agrícola, Escola do Movimento dos Trabalhadores Sem Terra e Escola Multisseriada. Têm nos estudos de Vigotski (2005), Benjamin (1994) e Larrosa (2002) as contribuições que fundamentam a compreensão de sentidos e experiência, estes como produção subjetiva, temporal e singular que ecoam das vozes dos sujeitos. As narrativas como perspectiva metodológica da pesquisa são aqui adotadas como as histórias de práticas em situação (BERTAUX, 2010) ou histórias de vida que pensam um projeto (JOSSO, 2002) e que por assim se constituírem tem como ponto motivador nos diálogos a formação e a profissão docente no campo. Trata-se, de uma narrativa de vida situada, a partir de um impulso que proporciona ao narrador e seu interlocutor o adentrar de uma história que se faz em meio a pessoas, memórias, sentimentos, conflitos, práticas e todo um contexto acerca do impulso de suas experiências de vida, formação e profissão. A partir da escuta em diálogo com as questões da pesquisa registramos a escrita dos sentidos produzidos, não como universais, mas como heterogêneos e simultaneamente singulares aos sujeitos. Nessa perspectiva, os sujeitos produzem diferentes sentidos na relação formação e profissionalização, estes amalgamados e relacionados às suas aspirações com a formação continuada e a carreira docente, imbricados nas itinerâncias dos movimentos sociais nos quais militam, bem como, nas memórias e trajetórias na educação. Pensar, portanto, em processos de formação continuada de professores do campo, à luz dessa discussão, é abrir-se aos diferentes contornos que esta assume a partir dos sentidos produzidos pelos sujeitos, desafiando-nos à construção de projetos que dialoguem com a diversidade da educação do campo e que se colocam como espaçostempos da reflexão do ser e/ou estar professor (a)-monitor (a)-educador (a) do campo.

Formação, educação física e inclusão : compreendendo os processos inclusivos

No intuito de contribuir para a problematização da Educação, numa perspectiva inclusiva, esta dissertação procura conhecer e analisar a prática pedagógica inclusiva experimentada pelos professores de Educação Física na escola, por meio de suas narrativas, em uma ação de formação continuada. O projeto de extensão intitulado Formação Continuada de Professores de Educação Física para a Educação Inclusiva foi a estratégia utilizada para a criação de um grupo de estudos, denominado Grupo Operativo de Formação (GOF). A ação de formação continuada foi realizada durante o período de julho a dezembro de 2011, em um encontro presencial semanal, totalizando dezesseis encontros, com uma carga horária final de 90h. Participaram da ação de formação quatro professores da Secretaria Municipal de Educação de Vitória-ES. A pesquisa baseia-se em elementos da pesquisa-ação, utilizando como instrumentos e procedimentos para a produção dos dados a narrativa, o diário de campo, o memorial e a entrevista. Da análise dos dados produzidos identifica três categorias norteadoras das discussões: a) o trabalho coletivo como possibilidade para inclusão; b) trilhando caminhos para o desenvolvimento de práticas inclusivas: o autismo como foco do percurso; c) o olhar dos professores sobre a ação de formação experimentada no GOF. As análises realizadas revelam que essa ação de formação traz resultados que sinalizam positivamente para sua efetivação como instrumento ativo no processo de formação de professores para a educação básica, na perspectiva da inclusão. Portanto, essa é uma interessante ferramenta a ser utilizada pelas redes de ensino como alternativa metodológica em programas de formação continuada. Além disso, a proposta promove momentos para a prática reflexiva dos professores, representando uma rica oportunidade, capaz de fazer com que eles se apropriem de teorias educacionais que poderão contribuir na elaboração de suas aulas.