Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis

Background The mechanisms responsible for disturbed iron homoeostasis in hereditary haemochromatosis are poorly understood. However, results of some studies indicate a link between hepcidin, a liver-derived peptide, and intestinal iron absorption, suggesting that this molecule could play a part in hepatic iron overload. To investigate this possible association, we studied the hepatic expression of the gene for hepcidin (HAMP) and a gene important in iron transport (IREG1) in patients with haemochromatosis, in normal controls, and in Hfe-knockout mice. Methods We extracted total RNA from the liver tissue of 27 patients with HFE-associated haemochromatosis, seven transplant donors (controls), and Hfe-knockout mice. HAMP and IREG1 mRNA concentrations were examined by ribonuclease protection assays and expressed relative to the housekeeping gene GAPD. Findings There was a significant decrease in HAMP expression in untreated patients compared with controls (5.4-fold, 95% CI 3.3-7.5; p

Independent contribution of plaque complexity to myocardial ischemia during Dobutamine stress echocardiography

The influence of complex plaque morphology on the extent of demand-induced ischemia in unselected patients is not well defined. We sought to investigate the functional significance of lesion morphology in patients who underwent coronary angiography and dobutamine stress echocardiography (DSE).,Angiography and DSE were performed within a 6-month period (mean 1 +/- 1 month) in 196 patients. Angiographic assessments involved quantification of stenosis severity, assessment of the extent of jeopardized myocardium, and categorization of plaque morphology according to the Ambrose classification. DSE was interpreted by separate investigators with respect to wall motion score index (WMSI) and number of coronary territories involved. A general linear model was constructed to assess,the independent contribution of patient characteristics and angiographic and DSE results with respect to extent of ischemic myocardium. Complex lesion morphology was seen in 62 patients (32%). Patients with complex lesions were more likely to have had prior myocardial infarction (p < 0.001) and be current smokers (p = 0.03). During angiography, they exhibited a trend toward a greater number of diseased vessels, had a greater coronary jeopardy score (p < 0.001) and more frequent collateral flow (p = 0.03). During echocardiography, patients had a higher stress WMSI (p < 0.001) and were more likely to show ischemia in all 3 arterial territories (p < 0.01). On multivariate regression, the coronary artery jeopardy score and the presence of complex plaque morphology were independent predictors of the extent of ischemic myocardium (R 2 = 34%, p < 0.001). Thus, patients with complex plaque morphology are older, more likely to smoke, and more likely to have had prior myocardial. infarction. They exhibit more extensive disease with higher coronary jeopardy scores and a higher resting and peak stress WMSI. Despite these differences, complex plaque morphology remains an independent predictor of the extent of ischemia during stress. (C) 2003 by Excerpta Medica, Inc.

Comparison of the in vitro neuromuscular activity of venom from three Australian snakes (Hoplocephalus stephensi, Austrelaps superbus and Notechis scutatus): Efficacy of tiger snake antivenom

1. Tiger snake antivenom, raised against Notechis scutatus venom, is indicated not only for the treatment of envenomation by this snake, but also that of the copperhead (Austrelaps superbus ) and Stephen's banded snake (Hoplocephalus stephensi ). The present study compared the neuromuscular pharmacology of venom from these snakes and the in vitro efficacy of tiger snake antivenom. 2. In chick biventer cervicis muscle and mouse phrenic nerve diaphragm preparations, all venoms (3-10 mug/mL) produced inhibition of indirect twitches. In the biventer muscle, venoms (10 mug/mL) inhibited responses to acetylcholine (1 mmol/L) and carbachol (20 mumol/L), but not KCl (40 mmol/L). The prior (10 min) administration of 1 unit/mL antivenom markedly attenuated the neurotoxic effects of A. superbus and N. scutatus venoms (10 mug/mL), but was less effective against H. stephensi venom (10 mug/mL); 5 units/mL antivenom attenuated the neurotoxic activity of all venoms. 3. Administration of 5 units/mL antivenom at t(90) partially reversed, over a period of 3 h, the inhibition of twitches produced by N. scutatus (10 mug/mL; 41% recovery), A. superbus (10 mug/mL; 25% recovery) and H. stephensi (10 mug/mL; 50% recovery) venoms. All venoms (10-100 mug/mL) also displayed signs of in vitro myotoxicity. 4. The results of the present study indicate that all three venoms contain neurotoxic activity that is effectively attenuated by tiger snake antivenom.

Identification of cholinoceptive glycinergic neurons in the mammalian retina

The light-evoked release of acetylcholine (ACh) affects the responses of many retinal ganglion cells, in part via nicotinic acetylcholine receptors (nAChRs). nAChRs that contain beta2alpha3 neuronal nicotinic acetylcholine receptors have been identified and localized in the rabbit retina; these nAChRs are recognized by the monoclonal antibody mAb210. We have examined the expression of beta2alpha3 nAChRs by glycinergic amacrine cells in the rabbit retina and have identified different subpopulations of nicotinic cholinoceptive glycinergic cells using double and triple immunohistochemistry with quantitative analysis. Here we demonstrate that about 70% of the cholinoceptive amacrine cells in rabbit retina are glycinergic cells. At least three nonoverlapping subpopulations of mAb210 glycine-immunoreactive cells can be distinguished with antibodies against calretinin, calbindin, and gamma-aminobutyric acid (GABA)(A) receptors. The cholinergic cells in rabbit retina are thought to synapse only on other cholinergic cells and ganglion cells. Thus, the expression of beta2alpha3 nAChRs on diverse populations of glycinergic cells is puzzling. To explore this finding, the subcellular localization of beta2alpha3 was studied at the electron microscopic level. mAb210 immunoreactivity was localized on the dendrites of amacrines and ganglion cells throughout the inner plexiform layer, and much of the labeling was not associated with recognizable synapses. Thus, our findings indicate that ACh in the mammalian retina may modulate glycinergic circuits via extrasynaptic beta2alpha3 nAChRs. (C) 2002 Wiley-Liss, Inc.

Presta????o de contas: conv??nio entre MDS e prefeitura municipal

O estudo de caso trata da presta????o de contas, por uma prefeitura municipal, da aplica????o de recursos provenientes de um conv??nio com o Minist??rio de Desenvolvimento Social e Combate ?? Fome (MDS). A presta????o de contas foi aprovada e o texto apresenta a rela????o das atividades e gastos efetuados e observa????es feitas durante a avalia????o realizada pelo MDS. Este ?? um caso fict??cio usado em um curso de gest??o de conv??nios e de contratos de repasse de recursos

Conhecimento organizacional em escolas de governo: um estudo comparado

Como reflexo de uma tend??ncia que tem ganhado import??ncia crescente nas organiza????es p??blicas, privadas e n??o governamentais do Brasil e do mundo, a tem??tica gest??o do conhecimento motivou a realiza????o desta pesquisa, cujo foco imediato ?? fornecer subs??dios para auxiliar organiza????es p??blicas como escolas de governo em seus processos de desenvolvimento de conhecimento organizacional. Este conhecimento ?? criado mediante a intera????o dos conhecimentos t??cito e expl??cito. A intera????o entre eles pode ser verificada por meio de quatro convers??es, as quais formam um ciclo do conhecimento organizacional: a socializa????o, a externaliza????o, a combina????o e a internaliza????o. O estudo em quest??o visa apresentar um conjunto de crit??rios representantes do ciclo de desenvolvimento do conhecimento organizacional e, mediante an??lise comparada entre sete escolas de governo internacionais e uma nacional, a Funda????o Escola Nacional de Administra????o P??blica (Enap), elaborar o desenho de uma estrutura organizacional que maximize o desenvolvimento do conhecimento organizacional em escolas de governo.

C??rculo de controle de qualidade

Criada na d??cada de 40 para extrair min??rio de ferro dos dep??sitos do interior do Estado de Minas Gerais, aos poucos a Companhia Vale do Rio Doce (CVRD) expandiu suas atividades e ??reas de atua????o, de forma que hoje ?? a maior companhia exportadora de ferro, al??m de atuar na extra????o e beneficiamento de bauxita, ouro e outros minerais abundantes no Brasil. Com o prop??sito de elevar o rendimento das minas e a economicidade global do sistema, a CVRD adotou o processo de aglomera????o de min??rio por pelotiza????o e implantou seis usinas de pelotiza????o na ??rea de Tubar??o, no Estado do Esp??rito Santo. As usinas de pelotiza????o produzem pelotas de min??rio de ferro de alta qualidade. A pelotiza????o ?? um processo de aglomera????o da parcela ultrafina de min??rio ??? com o recurso de um processamento t??rmico ??? em esferas de di??metro adequado, com caracter??sticas de qualidade que permitam a sua aplica????o direta nos fornos sider??rgicos. A moagem ?? parte desse processo. Quando os moinhos est??o em opera????o normal, s??o programadas paradas para inspe????o do revestimento. Se h?? desgaste, programam-se paradas para trocar as barras de revestimento desgastadas

M??dulo 1 - gest??o de contratos de TI: curso Gest??o de Contratos de Tecnologia da Informa????o (GCTI)

Esse documento trata de:gest??o de contratos; legisla????o aplicada; elementos necess??rios para uma boa gest??o contratual; modelo de contrata????o; elementos do modelo (atores); elementos do modelo (artefatos;) elementos do modelo (processos e atividades); atividades do processo de inicia????o contratual; plano de inser????o

M??dulo 2 - monitoramento da execu????o contratual: curso Gest??o de Contratos de Tecnologia da Informa????o (GCTI)

Esse documento trata de: ordem de servi??o ou de fornecimento de bens; atividades e atores do monitoramento; recebimento provis??rio; recebimento definitivo; comando da SLTI/MP; responsabilidade por danos; responsabilidade por encargos; subcontrata????o; controle do material empregado; registro de ocorr??ncias; fiscaliza????o das obriga????es trabalhistas

M??dulo 3 - resultados, encerramento e transi????o contratual: curso Gest??o de Contratos de Tecnologia da Informa????o (GCTI)

Esse documento trata de: Hist??rico de Gerenciamento do Contrato; Avalia????o Qualitativa da Gest??o Contratual; Listas de Verifica????o; Metodologia Sugerida; O Processo; Avalia????o de Problemas e Ajustes Contratuais; Prazos Contratuais; Altera????es Contratuais; Inexecu????o e Rescis??o Contratual; Transi????o Contratual; Encerramento do Contrato; Procedimentos Necess??rios

Gest??o de Contratos de Tecnologia da Informa????o (GCTI)

Esse documento trata de: Gest??o Contratual; o Processo de Gerenciamento do Contrato; inicia????o Contratual; encaminhamento de Demandas; monitoramento da Execu????o Contratual; recebimento Provis??rio e Definitivo; ader??ncia Contratual; acompanhamento da Gest??o Contratual; tratamento de Anormalidades e Ajustes Contratuais; transi????o e Encerramento do Contrato

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