The Relationship between Blood and Serum Lead Levels in Peripartum Women and their Respective Umbilical Cords

Foetal exposure to lead (Pb) during pregnancy is a major problem. However, no previous study has examined whether Pb concentrations in blood (Pb-B) and in serum (Pb-S) from pregnant women correlate with Pb-B and Pb-S in the foetuses. This hypothesis was tested in the present study. We measured Pb-B and Pb-S in 120 healthy pregnant women (more than 38 weeks of gestation) and their respective umbilical cord samples. The analyses were carried out with an inductively coupled plasma mass spectrometer. We found higher Pb-B levels in the women compared with their respective umbilical cord samples (1.736 +/- 0.090 mu g/dL and 1.194 +/- 0.062 mu g/dL, respectively; p < 0.05). In parallel, we found higher Pb-S levels in the women compared with their respective umbilical cord samples (0.042 +/- 0.003 mu g/dL and 0.032 +/- 0.003 mu g/dL, respectively; p < 0.05). However, similar %Pb-S/Pb-B ratios were found in the women compared with their respective umbilical cord samples (2.414 +/- 0.210% and 2.740 +/- 0.219%, respectively; p > 0.05). Interestingly, we found positive correlations between Pb-B in the umbilical cords and Pb-B in the respective pregnant women (rs = 0.5714; p < 0.0001), and between Pb-S in the umbilical cords and Pb-S in the respective pregnant women (rs = 0.3902; p < 0.0001) as well as between %Pb-B/Pb-S in the umbilical cords and %Pb-B/Pb-S in the respective pregnant women (rs = 0.3767; p < 0.0001). These results indicate that the assessment of Pb-B and Pb-S in pregnant women provides relevant indexes of foetal exposure to Pb. Moreover, the similar %Pb-S/Pb-B in pregnant women and in the umbilical cords shows that the foetuses are directly exposed to the rapidly exchangeable Pb fraction found in their mothers.

Imbalance between matrix metalloproteinases and tissue inhibitor of metalloproteinases in hypertensive vascular remodeling

Structural vascular changes in two-kidney, one-clip (2K-1C) hypertension may result from increased matrix metalloproteinase (MMP)-2 activity. MMP-2 activation is regulated by other MMPs, including transmembrane-MMPs, and by tissue inhibitors of MMPs (TIMPs). We have investigated the localization of MMP-2, -9, -14, and TIMPs 1-4 in hypertensive aortas and measured their levels by zymography/Western blotting and immunohistochemistry. Gelatinolytic activity was assayed in tissues by in situ zymography. Sham-operated and 2K-1C hypertensive rats were treated with doxycycline (or vehicle) for 8 weeks, and the systolic blood pressure was monitored weekly. Doxycycline attenuated 2K-1C hypertension (165 +/- 11.7 mmHg versus 213 +/- 7.9 mm Hg in hypertensive controls, P<0.01), and completely prevented increase in the thicknesses of the media and the intima in 2K-1C animals (P<0.01). Increased amounts of MMP-2, -9, and -14 were found in hypertensive aortas, as well as enhanced gelatinolytic activity. A gradient in the localization of MMP-2, -9, and -14 was found, with increased amounts detected in the intima, at sites with higher gelatinolytic activity. Doxycycline attenuated hypertension induced increases in all the 3 investigated MMPs in both the media and the intima (all P<0.05). but it did not change the amounts of TIMPs 1-4 (P>0.05). Therefore, an imbalance between increased amounts of MMPs at the tissue level without a corresponding increase in the quantities of TIMPs, particularly in the intima and inner media layers, appears to account for the increased proteolytic activity found in 2K-1C hypertension-induced maladaptive vascular remodeling. (C) 2009 Elsevier B.V. All rights reserved.

A zebrafish homologue of deleted in colorectal cancer (zdcc) is expressed in the first neuronal clusters of the developing brain

DCC (deleted in colon cancer), Neogenin and UNC-5 are all members of the immunoglobulin superfamily of transmembrane receptors which are believed to play a role in axon guidance by binding to their ligands, the Netrin/UNC-40 family of secreted molecules (Cell. Mol. Life Sci. 56 (1999) 62; Curr. Opin. Genet. Dev. 7 (1997) 87). Although zebrafish homologues of the Netrin family of secreted molecules have been reported, to date there has been no published description of zebrafish DCC homologues (Mol. Cell. Neurosci. 9 (1997) 293., Mol. Cell. Neurosci. I I ( 1998) 194; Mech. Dev. 62 (1997) 147). We report here the expression pattern of a zebrafish dcc (zdcc) homologue during the initial period of neurogenesis and axon tract formation within the developing central nervous system. Between 12 and 33 h post-fertilisation zdcc is expressed in a dynamic spatiotemporal pattern in all major subdivisions of the central nervous system. Double-labelling for zdcc and the post-mitotic neuronal marker HNK-1 revealed that subpopulations of neurons within the first nuclei of the zebrafish brain express zdcc. These results support our previous observation that patterning of neuronal clusters in the zebrafish brain occurs early in development (Dev. Bioi, 229 (2001) 271). (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Geographical variation in the penetrance of CDKN2A mutations for melanoma

Background: Germline mutations in the CDKN2A gene, which encodes two proteins (p16INK4A and p14ARF), are the most common cause of inherited susceptibility to melanoma. We examined the penetrance of such mutations using data from eight groups from Europe, Australia and the United States that are part of The Melanoma Genetics Consortium Methods: We analyzed 80 families with documented CDKN2A mutations and multiple cases of cutaneous melanoma. We modeled penetrance for melanoma using a logistic regression model incorporating survival analysis. Hypothesis testing was based on likelihood ratio tests. Covariates included gender, alterations in p14APF protein, and population melanoma incidence rates. All statistical tests were two-sided. Results: The 80 analyzed families contained 402 melanoma patients, 320 of whom were tested for mutations and 291 were mutation carriers. We also tested 713 unaffected family members for mutations and 194 were carriers. Overall, CDKN2A mutation penetrance was estimated to be 0.30 (95% confidence interval (CI) = 0.12 to 0.62) by age 50 years and 0.67 (95% CI = 0.31 to 0.96) by age 80 years. Penetrance was not statistically significantly modified by gender or by whether the CDKN2A mutation altered p14ARF protein. However, there was a statistically significant effect of residing in a location with a high population incidence rate of melanoma (P = .003). By age 50 years CDKN2A mutation penetrance reached 0.13 in Europe, 0.50 in the United States, and 0.32 in Australia; by age 80 years it was 0.58 in Europe, 0.76 in the United States, and 0.91 in Australia. Conclusions: This study, which gives the most informed estimates of CDKN2A mutation penetrance available, indicates that the penetrance varies with melanoma population incidence rates. Thus, the same factors that affect population incidence of melanoma may also mediate CDKN2A penetrance.

Use of cyclic variation of integrated backscatter to assess contractile reserve and myocardial viability in chronic ischemic left ventricular dysfunction

The detection of viable myocardium has important implications for management, but use of stress echocardiography to detect this is subjective and requires exposure to dobutamine. We investigated whether cyclic variation (CV) of integrated backscatter (IB) from the apical views could provide a resting study for detection of contractile reserve (CR) and prediction of myocardial viability in 27 patients with chronic ischemic left ventricular (LV) dysfunction. Repeat echocardiography was performed after 6.7 +/- 3.8 months of follow-up; 14 patients underwent revascularization and 13 were treated medically. Using a standardized dobutamine echocardiography (DbE) protocol, images from three apical views were acquired at 80-120 frames/sec at rest and during stress. CR was identified if improvement of wall motion was observed at low dose (5 or 10 mug/kg/min) DbE. Myocardial viability was characterized by improvement at follow-up echocardiography in patients with revascularization. CVIB at rest and low dose dobutamine were assessed in 194 segments with resting asynergy (severe hypokinesis or akinesis), of which 88 (45%) were in patients who underwent revascularization. Of these, CVIB could be measured in 190 (98%) segments at rest and 185 (95%) at low dose dobutamine. Sixty-two (33%) segments had CR during low dose DbE and 50 (57%) segments showed wall-motion recovery (myocardial viability) at follow-up echocardiography. Segments with CR had significantly higher CVIB at rest (P < 0.001) and low dose dobutamine (P = 0.005) than segments without CR. Using optimal thresholds of CVIB (> 8.2 dB) at rest, the accuracy of CVIB for detecting CR was 70%. Compared with nonviable segments, viable segments had significantly higher CVIB at rest (P < 0.001) and low dose dobutamine (P < 0.001). Using optimal thresholds of CVIB (> 5.3 dB) at rest, the accuracy of CVIB for detecting myocardial viability was 85%, which was higher than that in conventional DbE (62%, P < 0.01). Thus, assessment of CV.TB from the apical views is a feasible and accurate tool for detecting CR and predicting myocardial viability in chronic LV dysfunction.

alpha-conotoxins PnIA and [A10L] PnIA stabilize different states of the alpha 7-L247T nicotinic acetylcholine receptor

The effects of the native alpha-conotoxin PnIA, its synthetic derivative [ A10L] PnIA and alanine scan derivatives of [ A10L] PnIA were investigated on chick wild type alpha7 and alpha7-L247T mutant nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes. PnIA and [A10L] PnIA inhibited acetylcholine (ACh)-activated currents at wtalpha7 receptors with IC50 values of 349 and 168 nM, respectively. Rates of onset of inhibition were similar for PnIA and [ A10L] PnIA; however, the rate of recovery was slower for [ A10L] PnIA, indicating that the increased potency of [ A10L] PnIA at alpha7 receptors is conveyed by its slower rate of dissociation from the receptors. All the alanine mutants of [ A10L] PnIA inhibited ACh-activated currents at wtalpha7 receptors. Insertion of an alanine residue between position 5 and 13 and at position 15 significantly reduced the ability of [ A10L] PnIA to inhibit ACh-evoked currents. PnIA inhibited the non-desensitizing ACh-activated currents at alpha7-L247T receptors with an IC50 194 nM. In contrast, [ A10L] PnIA and the alanine mutants potentiated the ACh-activated current alpha7-L247T receptors and in addition [ A10L] PnIA acted as an agonist. PnIA stabilized the receptor in a state that is non-conducting in both the wild type and mutant receptors, whereas [ A10L] PnIA stabilized a state that is non-conducting in the wild type receptor and conducting in the alpha7-L247T mutant. These data indicate that the change of a single amino acid side-chain, at position 10, is sufficient to change the toxin specificity for receptor states in the alpha7-L247T mutant.

Boletim eletr??nico de bibliografias especializadas: inova????o na gest??o p??blica

O 4?? Boletim Eletr??nico de Bibliografias Especializadas destaca o tema ???Inova????o na Gest??o P??blica???, com indica????es de livros e artigos de revistas pertencentes ao acervo da Biblioteca. O intuito ?? divulgar obras que auxiliem servidores p??blicos na transforma????o de processos de trabalho para melhor atender ao cidad??o.

Gerenciamento da qualidade total do INSS

A experi??ncia por n??s vivenciada no projeto piloto de Gerenciamento pela Qualidade Total, refor??a positivamente a nossa convic????o de que ?? poss??vel implementar esta mudan??a de cultura no SERVI??O P??BLICO, expandindo o projeto, por etapas, em todo o pa??s. Que esta mudan??a ?? centrada nas pessoas e que depende fundamentalmente do estabelecimento de uma VIS??O COMUM de Institui????o, de uma lideran??a que conquiste o comprometimento dos servidores e que crie espa??o para a valoriza????o das pessoas e o reconhecimento aos resultados atingidos

Texto para discuss??o 34: perfil dos gestores de recursos humanos na administra????o p??blica federal

O presente relat??rio visa divulgar informa????es sobre o perfil profissional dos gestores de recursos humanos da Administra????o P??blica Federal, resultantes de pesquisa realizada pela ENAP em 1998. A metodologia utilizada consistiu na consulta direta aos Gestores de Recursos Humanos GRHs por meio de um question??rio (composto por quest??es abertas e fechadas), enviado pelo correio, no m??s de outubro de 1998, a todo o universo poss??vel da pesquisa, ou seja, 194 ??reas de recursos humanos da administra????o p??blica federal, de acordo com os dados do Sistema de Pessoal Civil da Administra????o Federal (SIPEC). A amostra dosquestion??rios analisados foi de aproximadamente 24% do universo, ou 46 GRHs

Caf?? com debate: federalismo e integra????o nacional

Servidores p??blicos de diferentes ??rg??os do governo federal participaram na manh?? desta ter??a-feira (17) de mais uma edi????o do Caf?? com Debate. Para analisar o tema ???Federalismo e Integra????o Nacional???, estiveram na ENAP o presidente do F??rum das Federa????es, o canadense George Anderson, a cientista pol??tica Marta Arretche e o soci??logo Vicente Trevas. A experi??ncia profissional dos convidados possibilitou analisar diferentes aspectos do tema. George Anderson fez um apanhado sobre o desenvolvimento do federalismo no contexto mundial, destacando alguns pontos caracter??sticos do modelo brasileiro. Marta Arretche, que ?? docente na Universidade de S??o Paulo, abordou a quest??o sob a ??tica da Academia. A apresenta????o do ponto de vista do governo federal ficou a cargo de Vicente Trevas, que coordenou a Subchefia de Assuntos Federativos da Secretaria de Rela????es Institucionais da Presid??ncia da Rep??blica e atualmente assessora a Presid??ncia da Caixa Econ??mica Federal

Gest??o por compet??ncias: m??todos e t??cnicas para mapeamento de compet??ncias

A gest??o por compet??ncias tem sido apontada como alternativa aos modelos gerenciais tradicionalmente utilizados pelas organiza????es. Prop??e-se a orientar esfor??os para planejar, captar, desenvolver e avaliar, nos diferentes n??veis da organiza????o, as compet??ncias necess??rias ?? consecu????o de seus objetivos. Uma das principais etapas desse processo constitui o denominado mapeamento de compet??ncias. Este artigo objetiva apresentar m??todos, t??cnicas e instrumentos utilizados para mapeamento de compet??ncias em organiza????es p??blicas e privadas. Para isso, fazem-se uma revis??o da literatura sobre o conceito de compet??ncia, o mapeamento de compet??ncias e a gest??o por compet??ncias, discutindo-se seus pressupostos e suas aplica????es. Ao final, s??o levantadas as implica????es desse modelo de gest??o para o setor p??blico e s??o apresentadas recomenda????es pr??ticas.

Por uma carta latino-ibero-americana de compet??ncias comuns para dirigentes p??blicos: a proposta de Portugal

Nesta comunica????o, discutem-se as compet??ncias exigidas aos dirigentes pelos novos desafios de gest??o p??blica e prop??em-se as bases do que poder?? vir a constituir uma carta latino-iberoamericana sobre as compet??ncias que devem ser desenvolvidas e garantidas no grupo dirigente da Administra????o P??blica dos Estados representados no CLAD. Esta reflex??o baseia-se nos processos de diagn??stico e de forma????o que t??m vindo a ser promovidos pelo Instituto Nacional de Administra ????o no ??mbito da reforma da Administra????o P??blica em curso em Portugal.

Reformas pr??-mercado, rigidez constitucional e revis??o judicial: Brasil, Argentina e Uruguai em perspectiva comparada

Este artigo aborda a import??ncia da distribui????o de poderes de agenda e de veto dos cidad??os e dos Poderes Executivo, Legislativo e Judici??rio para viabilizar a implementa????o de reformas pr??-mercado no Brasil, na Argentina e no Uruguai em perspectiva comparada. Nesse sentido, o artigo aborda os temas da flexibilidade constitucional, da din??mica de forma????o das leis e da presen??a ou aus??ncia de revis??o judicial. A hip??tese subjacente a este artigo ?? a de que quanto mais r??gida a Constitui????o ??? vari??vel que envolve o poder de agenda e de veto dos cidad??os, do Executivo, do Legislativo e do Judici??rio ??? mais bem desenhado deve ser o jogo pol??tico para a viabiliza????o de implementa????o das reformas. Para exemplificar este artigo, foram analisadas as reformas previdenci??rias implantadas nos pa??ses em estudo.

Estrutura e organiza????o do poder executivo

Elaborado a partir dos relat??rios finais da pesquisa Estrutura e Organiza????o do Poder Executivo Frente ?? Op????o pelo Sistema de Governo, encomendada pela ENAP ao Centro de Estudos de Cultura Contempor??nea (CEDEC), dentro do projeto ENAP/PNUD BRA 90/017, este trabalho comp??e-se de dois volumes. O primeiro apresenta quatro estudos do sistema de governo e das rela????es entre administra????o p??blica e o sistema pol??tico na Alemanha, Fran??a, Gr??-Bretanha e It??lia. O segundo volume analisa o caso brasileiro, a partir de tr??s aspectos: profissionaliza????o do servi??o p??blico, moderniza????o do Estado e as rela????es entre administra????o e pol??tica, sintetizando as principais hip??teses, diagn??sticos e diretrizes de uma reforma administrativa.

Gravitational waves : a 100-year tool applied to the dark energy problem

Recent observations from type Ia Supernovae and from cosmic microwave background (CMB) anisotropies have revealed that most of the matter of the Universe interacts in a repulsive manner, composing the so-called dark energy constituent of the Universe. Determining the properties of dark energy is one of the most important tasks of modern cosmology and this is the main motivation for this work. The analysis of cosmic gravitational waves (GW) represents, besides the CMB temperature and polarization anisotropies, an additional approach in the determination of parameters that may constrain the dark energy models and their consistence. In recent work, a generalized Chaplygin gas model was considered in a flat universe and the corresponding spectrum of gravitational waves was obtained. In the present work we have added a massless gas component to that model and the new spectrum has been compared to the previous one. The Chaplygin gas is also used to simulate a L-CDM model by means of a particular combination of parameters so that the Chaplygin gas and the L-CDM models can be easily distinguished in the theoretical scenarios here established. We find that the models are strongly degenerated in the range of frequencies studied. This degeneracy is in part expected since the models must converge to each other when some particular combinations of parameters are considered.