(-)-CGP 12177 increases contractile force and hastens relaxation of human myocardial preparations through a propranolol-resistant state of the beta1-adrenoceptor

Two forms of the activated beta(1)-adrenoceptor exist, one that is stabilized by (-)-noradrenaline and is sensitive to blockade by (-)-propranolol and another which is stabilized by partial agonists such as (-)-pindolol and (-)-CGP 12177 but is relatively insensitive to (-)-propranolol. We investigated the effects of stimulation of the propranolol-resistant PI-adrenoceptor in the human heart. Myocardium from non-failing and failing human hearts were set up to contract at 1 Hz. In right atrium from non-ailing hearts in the presence of 200 nM (-)-propranolol, (-)-CGP 12177 caused concentration-dependent increases in contractile force (-logEC(50)[M] 7.3+/-0.1, E-max 23+/-1% relative to maximal (-)-isoprenaline stimulation of beta(1)- and beta(2)-adrenoceptors, n=86 patients), shortening of the time to reach peak force (-logEC(50)[M] 7.4+/-0.1, E-max 37+/-5%, n=61 patients) and shortening of the time to reach 50% relaxation (t(50%), -logEC(50)[M] 7.3+/-0.1, E-max 33+/-2%, n=61 patients). The potency and maxima of the positive inotropic effects were independent of Ser49Gly- and Gly389Arg-beta(1)-adrenoceptor polymorphisms but were potentiated by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (-logEC(50)[M] 7.7+/-0.1, E-max 68+/-6%, n=6 patients, P

Ozothamnus diosmifolius (Vent.) DC flower and leaf essential oils

Essential oils of rice flower, Ozothamnus diosmifolius, were analyzed by capillary gas chromatograplay-mass spectrometry. Flower oil contained beta-pinene (28.4%) and 1,8-cineole (28.2%), while the leaf oil contained a-pinene (26.0%), beta-pinene (11.6%) and 1,8-cineole (22.2%). Both oils had small amounts of spathulenol (4.1% and 5.2%, respectively).

Association of severe coronary stenosis with subclinical left ventricular dysfunction in the absence of infarction

Background. Regional left ventricular (LV) dysfunction may occur in patients with coronary artery disease (CAD) in the absence of infarction, but the causes of this phenomenon are unclear. We sought to identify whether changes in regional LV function were related to stenosis severity, using sensitive new ultrasound markers of function. Methods: We studied 67 individuals with no history of infarction and with normal LV systolic function: 49 patients with CAD and 18 control subjects without CAD. All patients underwent color Doppler tissue imaging, integrated backscatter (IB), anatomic M-mode echocardiography, and strain rate imaging to detect changes in structure and function. Peak early and late diastolic myocardial velocity, cyclic variation of IB, wall thickness, and percent wall thickening were measured in each basal and mid segment. Strain rate and peak systolic strain were calculated in each wall. CAD was defined as greater than or equal to 50% diameter stenosis. Normokinetic segments (n = 354) subtended by CAD were divided according to stenosis severity into 3 groups: group 1 (subtended by 50%-69% stenosis); group 2 (subtended by 70%-98% stenosis); and group 3 (subtended by greater than or equal to99% stenosis). Each parameter in each group was compared with that in 216 segments from control subjects. Results: Segments subtended by significant CAD showed lower peak early and late diastolic myocardial velocity compared with control segments. Group 3 showed significantly lower myocardial velocities than group 2 for both peak early (4.8 +/- 1.8 vs 6.0 +/- 2.0 cm/s, P

Effects of glucose-insulin-potassium infusion on chronic ischaemic left ventricular dysfunction

Background: Glucose-insulin-potassium (GIK) infusion improves cardiac function and outcome during acute ischaemia. Objective: To determine whether GIK infusion benefits patients with chronic ischaemic left ventricular dysfunction, and if so whether this is related to the presence and nature of viable myocardium. Methods: 30 patients with chronic ischaemic left ventricular dysfunction had dobutamine echocardiography and were given a four hour infusion of GIK. Segmental responses were quantified by improvement in wall motion score index (WMSI) and peak systolic velocity using tissue Doppler. Global responses were assessed by left ventricular volume and ejection fraction, measured using a three dimensional reconstruction. Myocardial perfusion was determined in 15 patients using contrast echocardiography. Results: WMSI (mean (SD)) improved with dobutamine (from 1.8 (0.4) to 1.6 (0.4), p < 0.001) and with GIK (from 1.8 (0.4) to 1.7 (0.4) p < 0.001); there was a similar increment for both. Improvement in wall motion score with GIK was observed in 55% of the 62 segments classed as viable by dobutamine echocardiography, and in 5% of 162 classed as non-viable. There was an increment in peak systolic velocity after both doputamine echocardiography (from 2.5 (1.8) to 3.2 (2.2) cm/s, p < 0.01) and GIK (from 3.0 (1.6) to 3.5 (17) cm/s, p < 0.001). The GlK effects were not mediated by changes in pulse, mean arterial pressure, lactate, or catecholamines, nor did they correlate with myocardial perfusion. End systolic volume improved after GlK (p = 0.03), but only in 25 patients who had viable myocardium on dobutom ne echocardiography. Conclusions: In patients with viable myocardium and chronic left ventricular dysfunction, GlK improves wall motion score, myocardial velocity, and end systolic volume, independent of effects on haemodynamics or catecholamines. The response to GlK is observed in areas of normal and abnormal perfusion assessed by contrast echocardiography.

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.

Decreased coumarin 7-hydroxylase activities and CYP2A6 expression levels in humans caused by genetic polymorphism in CYP2A6 promoter region (CYP2A6*9)

One of seven poor metabolizers of coumarin found in Thai subjects was previously genotyped as heterozygote for the CYP2A6*4 (whole deletion) and CYP2A6*9. Thus, we aimed to investigate the relationship between the genetic polymorphism in the TATA box of the CYP2A6 gene (CYP2A6*9), expression levels of CYP2A6 mRNA and coumarin 7-hydroxylase activities in human livers. Levels of CYP2A6 mRNA were quantified by real-time quantitative reverse transcriptase-polymerase chain reaction. The mean expression levels of CYP2A6 mRNA in individuals with CYP2A6*1/*4, CYP2A6*1/*9 and CYP2A6*4/*9 were 58%, 71% and 21% of the individuals genotyped as CYP2A6*1/*1, respectively. The mean in-vitro coumarin 7-hydroxylase activities in subjects carrying CYP2A6*1/*4, CYP2A6*1/*9 and CYP2A6*4/*9 were 41%, 71% and 12%, respectively, compared to those of the subjects judged as wild-type. Vmax values for coumarin 7-hydroxylation in the liver microsomes from human subjects with genotypes of CYP2A6*1/*1, CYP2A6*1/*4, CYP2A6*1/*9 and CYP2A6*4/*9 were 0.58, 0.26, 0.44 and 0.13 nmol/min/nmol total P450, respectively. CYP2A6 protein levels in human liver microsomes with the CYP2A6*4 and the CYP2A6*9 alleles were markedly decreased. These results suggest that the genetic polymorphism in the promoter region of the CYP2A6 gene (CYP2A6*9) reduced the expression levels of CYP2A6 mRNA and protein in human livers, resulting in the decrease of coumarin 7-hydroxylase activities. Individuals judged as CYP2A6*4/*9 were expected to be poor metabolizers, having extremely low activity of CYP2A6.

A kinetic study of the thermally initiated free radical reactions of styrene with octanedithiol as a model for the reactions of multifunctional thiols with divinylbenzene

The kinetics of chain reactions of octanedithiol with styrene, thermally initiated with TX29B50 (a 50:50 wt% solution of TX29 diperoxy initiator in a phthalate plasticizer), have been studied over a range of initiator concentrations, a range of mixture formulations and a range of temperatures. This system has been investigated as a model system for the reactions of polyfunctional thiols with divinyl benzene. The reactions have been shown to follow first-order kinetics for both the thiol and the ene species and to be characterized by a dependence on the initiator concentration to the power of one half. The kinetic rate parameters have been shown to adhere to Arrhenius behaviour. A kinetic model for the chain reactions for this system has been proposed. (C) 2003 Society of Chemical Industry.

Escolas de governo e gest??o por compet??ncias: mesa-redonda de pesquisa-a????o

Dando sequ??ncia aos debates iniciados em 2004 e 2005 e que tiveram como produto o livro ???Gest??o por compet??ncias em organiza????es de governo???, a Mesa-redonda de Pesquisa-A????o vers??o 2009 prop??e-se a suprir uma lacuna importante: discutir a atua????o do Sistema de Escolas de Governo da Uni??o em face das diretrizes da Pol??tica Nacional de Desenvolvimento de Pessoal (PNDP) ??? Decreto n?? 5.707 de 23 de fevereiro de 2006

Relat??rio de Gest??o 2011

Relat??rio de Gest??o do exerc??cio de 2011 apresentado aos ??rg??os de controle interno e externo como presta????o de contas anual a que esta Unidade est?? obrigada nos termos do art. 70 da Constitui????o Federal, elaborado de acordo com as disposi????es da IN TCU n?? 63/2010, da DN TCU n?? 108/2010, da Portaria TCU n?? 123/2011 e das orienta????es do ??rg??o de controle interno (Portaria CGU n?? 2546/2010)

Sistematiza????o normativa e tipologia preliminar de organiza????es federais

O segundo volume da s??rie Inova????o na Gest??o P??blica trata de estudo realizado pela consultora Suely Komatsu sobre estruturas organizacionais do Governo Federal. O trabalho foi realizado em agosto de 2009 e, portanto, traz um retrato das estruturas ?? ??poca da pesquisa. Apesar do lapso temporal de tr??s anos, o estudo permanece relevante e atual. A publica????o ?? composta por tr??s cap??tulos. O Cap??tulo 1 traz a consolida????o e an??lise da evolu????o das reformas administrativas que orientamos arranjos institucionais e organizacionais no pa??s. O Cap??tulo 2, por sua vez, apresenta o levantamento e a sistematiza????o de marcos legais e orienta????es normativas relevantes para defini????o de estruturas organizacionais nas ??reas meio e final??stica. Por fim, o Cap??tulo 3 identifica par??metros comuns e compar??veis nos arranjos organizacionais, com a proposi????o de uma tipologia inicial de estruturas organizacionais da esfera federal tendo como base as seguintes vari??veis: ???concentra????o das atribui????es principais???, ???natureza jur??dico- -institucional???, ???grau de descentraliza????o das principais atividades???, ???n??mero de subunidades em cada n??vel hier??rquico??? e ???amplitude de comando???

Jornal ENAP 1996

Reuni??o das edi????es de 1996 do Jornal ENAP, o qual publicava informa????es institucionais e/ou correlatas ?? administra????o p??blica.

A carreira de especialista em pol??ticas p??blicas e gest??o governamental e o fortalecimento do estado brasileiro

Buscou-se ter um quadro de funcion??rios, recrutados por concurso, que fosse permanente e qualificado para a formula????o, implementa????o e avalia????o de pol??ticas p??blicas como atividade inerente ao governo. N??o podemos ver como carreira se n??o for para atuar no governo, como n??cleo de recursos humanos estrat??gicos, respons??vel para dar suporte a atividade governamental.

O contexto da cria????o da carreira de especialista em pol??ticas p??blicas e gest??o governamental

O artigo tr??s uma apresenta????o da experi??ncia do autor, do hist??rico da cria????o da Escola Nacional de Administra????o P??blica (ENAP), dentro do qual a carreira de gestor p??blico tem um papel importante.

O impacto da exposição a experiências adversas na infância na ocorrência de dor crônica e depressão na vida adulta

A associação entre experiências adversas na infância e o desencadeamento de depressão ou dor crônica na vida adulta tem sido documentada, assim como a relação entre os sintomas de dor crônica e depressão. No entanto, há poucos estudos avaliando o papel da exposição a experiências adversas na infância na ocorrência dessa comorbidade. O objetivo deste trabalho é avaliar a influência da exposição a experiências adversas na infância na ocorrência de dor crônica, de depressão e na comorbidade dor crônica e depressão na vida adulta, em uma amostra da população geral adulta (maiores de 18 anos) residente na Região metropolitana de São Paulo, Brasil. Os dados são resultantes do Estudo Epidemiológicos dos Transtornos Mentais São Paulo Megacity. Os respondentes foram avaliados usando a versão desenvolvida para o Estudo Mundial de Saúde Mental do Composite International Diagnostic Interview da Organização Mundial da Saúde (WMH-CIDI), que é composto por módulos clínicos e nãoclínicos provendo diagnósticos de acordo com os critérios do Manual Diagnóstico e Estatístico dos Transtornos Mentais 4ª edição (DSM-IV). Um total de 5.037 indivíduos foi entrevistado, com uma taxa global de resposta de 81,3%. Foram realizadas análises descritivas para médias e proporções, e associações (Razões de Chances – OR) entre experiências adversas na infância, dor crônica e depressão através de regressão logística. Todas as análises foram realizadas através do programa estatístico Data Analysis and Statistical Software versão 12.0 (STATA 12.0), com testes bi-caudais com nível de significância de 5%. Uma elevada taxa de prevalência de dor crônica (31%, Erro Padrão [ER]=0.8) foi encontrada, Dor Crônica esteve associada aos transtornos de ansiedade (OR=2,3; 95% IC=1,9 – 3,0), transtornos de humor (OR=3,3; IC=2,6 – 4,4) em qualquer transtorno mental (OR=2,7; 95% IC=2,3 – 3,3). As adversidades na infância estiveram fortemente associadas aos respondentes com dor crônica e depressão concomitante, principalmente quanto ao abuso físico (OR=2,7; 95% IC=2,1 – 3,5) e sexual (OR=7,4; 95% IC=3,4 – 16,1).

Avaliação do risco cardiovascular e fatores associados na população de Anchieta-ES

As doenças cardiovasculares são as principais causas de morte no mundo e muitos constituem os fatores de risco para essas doenças. Objetiva-se investigar o risco cardiovascular para evento coronariano agudo de acordo com o escore de Framingham em população adulta do município de Anchieta-ES. Estudo transversal com dados da linha de base do estudo Carmen Anchieta, iniciado em 2010. A amostra foi sistemática e estratificada por micro área de abrangência das Unidades de Saúde da Família, sexo e idade e 539 pessoas foram selecionadas para este estudo por terem os dados completos. Os dados foram coletados mediante entrevista no domicílio, exames laboratoriais de sangue, verificação da pressão arterial e antropometria nas Unidades de Saúde. As variáveis de exposição constituem escolaridade, raça-cor, renda familiar, residência em espaço urbano ou rural, estado civil, consumo de álcool, atividade física, índice de massa corpórea e autoavaliação de saúde. Para a classificação do risco cardiovascular utilizou-se o escore de Framingham. Foi realizada análise bivariada e regressão logística multinomial para testar a hipótese de associação entre as variáveis e o risco cardiovascular mediante o cálculo da razão de chances (RC) e intervalo de confiança de 95%. O nível de significância foi p < 0,05. Os resultados mostraram predominância de pessoas nas faixas etárias entre 25 a 54 anos, casadas, pardas, ensino fundamental incompleto, baixa renda, insuficientemente ativas, com sobrepeso e obesidade em mais da metade da amostra, 38,6% ingeriam bebida alcoólica e 55,7% relaram saúde muito boa ou boa. O risco cardiovascular foi baixo em 74%, intermediário em 11,3% e elevado em 14,7%. Estiveram associados ao risco cardiovascular intermediário ser analfabeto 8,89 (3,193-24,756), ter ensino fundamental incompleto 3,17 (1,450-6,964) e ser viúvo/ separado 2,55 (1,165-5,583) e associados ao risco cardiovascular elevado ser analfabeto 11,34 (4,281-30,049), ensino fundamental incompleto 2,95 (1,362-6,407) e autoavaliação da saúde muito ruim/ruim 2,98 (1,072-8,307) e regular 2,25 (1,294-3,925). Ser solteiro constituiu fator de proteção 0,40 (0,183-0,902).