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.

Alterations of neocortical pyramidal cell phenotype in the Ts65Dn mouse model of Down syndrome: Effects of environmental enrichment

Mental retardation in individuals with Down syndrome (DS) is thought to result from anomalous development and function of the brain; however, the underlying neuropathological processes have yet to be determined. Early implementation of special care programs result in limited, and temporary, cognitive improvements in DS individuals. In the present study, we investigated the possible neural correlates of these limited improvements. More specifically, we studied cortical pyramidal cells in the frontal cortex of Ts65Dn mice, a partial trisomy of murine chromosome 16 (MMU16) model characterized by cognitive deficits, hyperactivity, behavioral disruption and reduced attention levels similar to those observed in DS, and their control littermates. Animals were raised either in a standard or in an enriched environment. Environmental enrichment had a marked effect on pyramidal cell structure in control animals. Pyramidal cells in environmentally enriched control animals were significantly more branched and more spinous than non-enriched controls. However, environmental enrichment had little effect on pyramidal cell structure in Ts65Dn mice. As each dendritic spine receives at least one excitatory input, differences in the number of spines found in the dendritic arbors of pyramidal cells in the two groups reflect differences in the number of excitatory inputs they receive and, consequently, complexity in cortical circuitry. The present results suggest that behavioral deficits demonstrated in the Ts65Dn model could be attributed to abnormal circuit development.

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.

A yield architecture framework to explain adaptation of pearl millet to environmental stress

Functional knowledge of the physiological basis of crop adaptation to stress is a prerequisite for exploiting specific adaptation to stress environments in breeding programs. This paper presents an analysis of yield components for pearl millet, to explain the specific adaptation of local landraces to stress environments in Rajasthan, India. Six genotypes, ranging from high-tillering traditional landraces to low-tillering open-pollinated modern cultivars, were grown in 20 experiments, covering a range of nonstress and drought stress patterns. In each experiment, yield components (particle number, grain number, 100 grain mass) were measured separately for main shoots, basal tillers, and nodal tillers. Under optimum conditions, landraces had a significantly lower grain yield than the cultivars, but no significant differences were observed at yield levels around 1 ton ha(-1). This genotype x environment interaction for grain yield was due to a difference in yield strategy, where landraces aimed at minimising the risk of a crop failure under stress conditions, and modem cultivars aimed at maximising yield potential under optimum conditions. A key aspect of the adaptation of landraces was the small size of the main shoot panicle, as it minimised (1) the loss of productive tillers during stem elongation; (2) the delay in anthesis if mid-season drought occurs; and (3) the reduction in panicle productivity of the basal tillers under stress. In addition, a low investment in structural panicle weight, relative to vegetative crop growth rate, promoted the production of nodal tillers, providing a mechanism to compensate for reduced basal tiller productivity if stress occurred around anthesis. A low maximum 100 grain mass also ensured individual grain mass was little affected by environmental conditions. The strategy of the high-tillering landraces carries a yield penalty under optimum conditions, but is expected to minimise the risk of a crop failure, particularly if mid-season drought stress occurs. The yield architecture of low-tillering varieties, by contrast, will be suited to end-of-season drought stress, provided anthesis is early. Application of the above adaptation mechanisms into a breeding program could enable the identification of plant types that match the prevalent stress patterns in the target environments. (C) 2003 E.J. van Oosterom. Published by Elsevier Science B.V. All rights reserved.

Plano de implementa????o do projeto de desenvolvimento de capacidade de governan??a

Desde a d??cada de 1990, o Governo Federal brasileiro vem implementando uma agenda ambiciosa de reformas do Estado, centradas na redu????o da pobreza e na melhoria da efici??ncia dos servi??os p??blicos. As principais prioridades, conforme previstas no Plano Plurianual (PPA) para o per??odo 2003-2007, s??o as seguintes: inclus??o social e redu????o da desigualdade; crescimento econ??mico com gera????o de emprego; distribui????o de renda e respeito ao meio ambiente; promo????o e amplia????o dos direitos de cidadania; e fortalecimento da democracia. No in??cio de 2006, o Governo criou a Pol??tica Nacional de Desenvolvimento de Pessoal (Decreto 5.707), com o objetivo de melhorar e aumentar a efici??ncia e a efic??cia na presta????o de servi??os p??blicos. No marco dessa pol??tica recente, as escolas de administra????o p??blica desempenham um papel fundamental na identifica????o das compet??ncias que precisam ser desenvolvidas nas institui????es do governo, bem como na implementa????o de pol??ticas de capacita????o para os servidores p??blicos, diretamente e/ou em parceria com escolas de governo nos n??veis federal, estadual ou local. O Canad?? tamb??m est?? criando uma estrutura para levantar as compet??ncias necess??rias para os servidores p??blicos e desenvolv??-las como um componente da Renova????o do Servi??o P??blico em todo o governo. Como institui????es l??deres no desenvolvimento de compet??ncias de servidores p??blicos, a Canada School of Public Service (CSPS) e a Escola Nacional de Administra????o P??blica (ENAP) firmaram uma parceria para implementar o Projeto de Desenvolvimento de Capacidade de Governan??a no Brasil. A finalidade do Projeto ?? melhorar a capacidade de servidores p??blicos federais, estaduais e municipais do Brasil para desenvolver e implementar programas de capacita????o e gerenciar pol??ticas p??blicas descentralizadas. Espera-se que essa parceria e o resultante compartilhamento de experi??ncias em capacita????o para governan??a efetiva contribuam para a redu????o da pobreza e das desigualdades no Brasil, por meio do desenvolvimento de compet??ncias de servidores na presta????o de servi??os p??blicos eficazes e eficientes, voltados para o cidad??o. O Projeto re??ne, al??m das duas principais Escolas de Governo no Canad?? e no Brasil, seis Escolas Brasileiras de Administra????o P??blica regionais e duas renomadas Institui????es Acad??micas Canadenses ??? a Queen???s University e a Western Ontario University. O Minist??rio do Desenvolvimento Social e Combate ?? Fome (MDS) e tr??s Secretarias Especiais do Governo Federal ??? Ra??a (SEPPIR), Direitos Humanos (SEDH) e Pol??ticas para as Mulheres (SPM) ??? tamb??m se envolver??o nas atividades de compartilhamento de conhecimentos com o Human Resources and Skills Development Canada (HRSDC) e a Canada Public Service Agency (CPSA). A CIDA fornecer?? CND$1.700.000 por meio do Programa Brasil-Canad?? de Interc??mbio de Conhecimentos para a Promo????o da Equidade (PIPE). A contribui????o da ENAP ser?? de CND$1.069.707 em esp??cie. A CSPS contribuir?? com cursos, al??m de conhecimentos e suporte t??cnicos, avaliados em CND$1.000.000. Aproveitando a parceria entre a CSPS e a ENAP, que resultou na transfer??ncia e na adapta????o bem sucedidas de cursos e metodologias canadenses, o novo projeto extrapola o n??cleo do servi??o p??blico em Bras??lia, alcan??ando escolas de governo em regi??es brasileiras em situa????o de desvantagem. ?? semelhan??a do papel da CSPS no primeiro projeto, a ENAP fortalecer?? a capacidade das escolas parceiras regionais para capacitar servidores p??blicos envolvidos na presta????o de servi??os aos brasileiros. O interc??mbio estruturado entre Minist??rios dos Governos canadense e brasileiro tamb??m aplicar?? a aprendizagem mais diretamente a quest??es de pol??ticas e programas sociais do Brasil. O desafio assumido neste Projeto ?? a adapta????o de conhecimentos e aprendizagem, com vistas a melhorar a implementa????o de pol??ticas e programas sociais. Para tanto, a CSPS e a ENAP introduzir??o novos cursos nos curr??culos das escolas parceiras e incorporar??o novos m??todos e tecnologias de aprendizagem como, por exemplo, comunidades de pr??tica virtuais e um componente de tutoria (mentoring) envolvendo o Human Resources and Skills Development Canada e o Minist??rio do Desenvolvimento Social e Combate ?? Fome do Brasil. Seis institui????es da Rede Nacional de Escolas de Governo do Brasil e do Programa de Parceria da ENAP foram selecionadas e convidadas a se unir ?? CSPS e ?? ENAP nesse novo Projeto: a Universidade Federal do Par?? (UFPA), de Bel??m (estado do Par?? ??? regi??o Norte); a Funda????o Joaquim Nabuco (FUNDAJ), de Recife (Pernambuco ??? Nordeste); a Universidade Corporativa do Servi??o P??blico / Secretaria de Administra????o do Estado da Bahia (UCS/SAEB), Salvador (Bahia ??? Nordeste); a Escola de Governo do Mato Grosso do Sul (ESCOLAGOV), Campo Grande (estado do Mato Grosso do Sul ??? Centro-Oeste); a Escola Nacional de Ci??ncias Estat??sticas / Instituto Brasileiro de Geografia e Estat??stica (ENCE/IBGE), Rio de Janeiro (estado do Rio de Janeiro ??? Sudeste); e o Instituto Municipal de Administra????o P??blica (IMAP) de Curitiba (Paran?? ??? Sul). Essas escolas de refer??ncia foram escolhidas segundo sua capacidade de trabalhar como p??los de pr??ticas inovadoras em pol??ticas p??blicas e disseminar os benef??cios do Projeto para outras escolas em suas regi??es, por meio da Rede Nacional coordenada pela ENAP. O objetivo dessa parceria ?? fortalecer as escolas de governo locais, para que estas desenvolvam, por meio de eventos de aprendizagem, compet??ncias em servidores p??blicos, a fim de aumentar a capacidade do governo na implementa????o e gest??o de pol??ticas p??blicas. O Plano de Implementa????o do Projeto (PIP) descreve o trabalho a ser realizado por essas institui????es nos pr??ximos 30 meses, ao tempo em que serve de guia para os Parceiros do Projeto no que se refere ??s a????es e aos recursos necess??rios para a obten????o dos resultados acordados. Na medida em que o Projeto estiver em andamento e os parceiros iniciarem um interc??mbio produtivo de conhecimentos, o Plano de Trabalho Anual ser?? atualizado e revisto por meio de reuni??es anuais de avalia????o e encontros do Comit?? Diretor do Projeto, com vistas a assegurar que os resultados descritos no PIP sejam alcan??ados com sucesso

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.

Liberação de nutrientes pela palhada de milheto em diferentes estádios fenológicos

Trabalho apresentado no XXXI Congresso Brasileiro de Ciência do Solo (2007 : Gramado, RS)

Bone mineral density of rat femurs after hindlimb unloading and different physical rehabilitation programs

Bone weakening can occur due to the absence of load on the skeleton or even short periods of decreased physical activity. Therefore, musculoskeletal diseases that involve temporary immobilization by casts, inactivity or tension increases the risk of fractures. Physical activity is the most studied procedure both to prevent damage and to restore bone structure. The present study aimed at evaluating, by bone densitometry on rat femurs, the influence of hindlimb unloading and later running activity on treadmill or free movement. Sixty-four Wistar rats were used, aged 65 days with a mean corporal mass of 316.11g, randomly divided into eight experimental groups: group 1, the suspended control with seven animals under hindlimb unloading regimen for 28 days, then euthanized; groups 2 and 3, the trained suspended comprising of 7 and five animals, respectively, subjected to hindlimb unloading for 28 days, followed by treadmill exercise for 28 days (group 2) or 56 days (group 3), then euthanized; groups 4 and 5, designated free suspended, comprised of 7 animals each under hindlimb unloading regimen for 28 days followed by free activity in cages for 28 days (group 4) or 56 days (group 5), then euthanized; groups 6, 7 and 8, negative controls, each with 8 animals allowed to free activity in cages and euthanized at the ages of 93, 121 and 149 days, respectively. Bone mineral density (BMD) of the left femur was analyzed by bone densitometry. Unloading by tail-suspension decreased BMD while treadmill training and free activity in cages promoted its recovery in a similar way and over time.

Identifying clones in functional programs for refactoring

Clone detection is well established for imperative programs. It works mostly on the statement level and therefore is ill-suited for func- tional programs, whose main constituents are expressions and types. In this paper we introduce clone detection for functional programs using a new intermediate program representation, dubbed Functional Control Tree. We extend clone detection to the identi cation of non-trivial func- tional program clones based on the recursion patterns from the so-called Bird-Meertens formalism

Criminal Liability of Organizations, Corporations, Legal Persons, and Similar Entities on Law of Portuguese Cybercrime: A Brief Discussion on the Issue of Crimes of “False Information,” the “Damage on Other Programs or Computer Data,” the “Computer-Software Sabotage,” the “Illegitimate Access,” the “Unlawful Interception,” and “Illegitimate Reproduction of the Protected Program”

Abstract: in Portugal, and in much of the legal systems of Europe, «legal persons» are likely to be criminally responsibilities also for cybercrimes. Like for example the following crimes: «false information»; «damage on other programs or computer data»; «computer-software sabotage»; «illegitimate access»; «unlawful interception» and «illegitimate reproduction of protected program». However, in Portugal, have many exceptions. Exceptions to the «question of criminal liability» of «legal persons». Some «legal persons» can not be blamed for cybercrime. The legislature did not leave! These «legal persons» are v.g. the following («public entities»): legal persons under public law, which include the public business entities; entities utilities, regardless of ownership; or other legal persons exercising public powers. In other words, and again as an example, a Portuguese public university or a private concessionaire of a public service in Portugal, can not commit (in Portugal) any one of cybercrime pointed. Fair? Unfair. All laws should provide that all legal persons can commit cybercrimes. PS: resumo do artigo em inglês.