Early rise in blood pressure following administration of adrenocorticotropic hormone-[1-24] in humans

1. An elevation in blood pressure has been consistently observed 24 h after adrenocorticotropic hormone (ACTH) administration and is caused by increased ACTH-stimulated cortisol secretion, in association with increased cardiac output. The aim of the present study was to investigate the previously undefined time of onset of this increase in blood pressure in normal humans. 2. Ten normal healthy volunteers received 250 mug ACTH-[1-24], in 500 mL normal saline, infused at a constant rate over 8 h. Six subjects also received a placebo infusion (normal saline only). Blood pressure, heart rate and cortisol levels were determined hourly. Adrenocorticotropic hormone (ACTH-[1-24] plus native ACTH) was measured at 0, 1, 7 and 8 h. 3. Infusion of ACTH-[1-24] produced maximal secretion rates of cortisol, resulting in a mean peak plasma level of 985 +/- 46 nmol/L at 8 h. In response, blood pressure and heart rate rose significantly by 2 h and remained generally elevated for the duration of the infusion. 4. The early onset of haemodynamic responses is consistent with classical steroid receptor-mediated genomic mechanisms, but could be due non-genomic mechanisms. 5. The cardiovascular consequences of therapeutic use of ACTH are well recognized. This results of the present study suggest that even diagnostic administration of ACTH, delivered over a few hours, may raise blood pressure.

Route of administration of chimeric BPV1VLP determines the character of the induced immune responses

To examine the mucosal immune response to papillomavirus virus-like particles (PV-VLP), mice were immunized with VLP intrarectally (i.r.), intravaginally (i.va.) or intramuscularly (i.m.) without adjuvant. PV-VLP were assembled with chimeric BPV-1 L1 proteins incorporating sequence from HIV-1 gp 120, either the V3 loop or a shorter peptide incorporating a known CTL epitope (HIVP18I10). Antibody specific for BPV-1 VLP and P18 peptide was detected in serum following i.m., but not i.r. or i.va. immunization. Denatured VLP induced a much reduced immune response when compared with native VLP, Immune responses following mucosal administration of VLP were generally weaker than following systemic administration. VLP specific IgA was higher in intestine washes following i.r. than i.va. immunization, and higher in vaginal washes following i.m. than i.r. or i.va. immunization. No differences in specific antibody responses were seen between animals immunized with BPV-1 P18 VLP or with BPV-1 V3 VLP. Cytotoxic T lymphocyte precursors specific for the P18 CTL epitope were recovered from the spleen following i.m., i.va. or i.r. immunization with P18 VLP, and were similarly detected in Peyer's patches following i.m. or i.r. immunization. Thus, mucosal or systemic immunization with PV VLP induces mucosal CTL responses and this may be important for vaccines for mucosal infection with human papillomaviruses and for other viruses.

Oral administration of a 12% sucrose solution did not decrease behavioural indicators of distress in piglets undergoing tail docking, teeth clipping and ear notching

Sucrose has been shown to attenuate the behavioural response to painful procedures in human infants undergoing circumcision or blood collection via heelstick. Sucrose has also been found to have a behaviour-modifying effect in neonatal rats exposed to a hot plate. The effect was abolished in neonatal rats by injection of the opioid antagonist naltrexone, suggesting that it was mediated by endogenous opioids. In this experiment, the behaviour of 571 newborn Large White x Landrace hybrid piglets in a specific-pathogen-free piggery of the University of Queensland was recorded during and after the routine management practices of tail docking, ear notching and teeth clipping. Piglets were randomly assigned to receive 1.0 ml of a 12% sucrose solution (treatment group) or a placebo (1.0 ml of air) administered via syringe in the mouth, 60 s before commencement of one of the management procedures. Behaviours were recorded at the time of the procedure, and then 2 min after completion of the procedure. Piglets that received the sucrose solution did not behave significantly differently from piglets receiving the placebo. Regardless of whether sucrose or placebo was administered, piglets undergoing the routine management procedures showed significantly greater behavioural responses than piglets undergoing no procedure. It was concluded that under commercial conditions, a 12% sucrose solution administered I min prior to surgery was not effective in decreasing the behavioural indicators of distress in piglets undergoing routine management procedures, Further research into methods of minimising distress caused to piglets by these procedures is recommended.

Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum

Background The ability of T cells, acting independently of antibodies, to control malaria parasite growth in people has not been defined. If such cell-mediated immunity was shown to be effective, an additional vaccine strategy could be pursued. Our aim was to ascertain whether or not development of cell-mediated immunity to Plasmodium falciparum blood-stage infection could be induced in human beings by exposure to malaria parasites in very low density. Methods We enrolled five volunteers from the staff at our research institute who had never had malaria. We used a cryopreserved inoculum of red cells infected with P falciparum strain 3D7 to give them repeated subclinical infections of malaria that we then cured early with drugs, to induce cell-mediated immune responses. We tested for development of immunity by measurement of parasite concentrations in the blood of volunteers by PCR of the multicopy gene STEVOR and by following up the volunteers clinically, and by measuring antibody and cellular immune responses to the parasite. Findings After challenge and a extended period without drug cure, volunteers were protected against malaria as indicated by absence of parasites or parasite DNA in the blood, and absence of clinical symptoms. Immunity was characterised by absence of detectable antibodies that bind the parasite or infected red cells, but by the presence of a proliferative T-cell response, involving CD4+ and CD8+ T cells, a cytokine response, consisting of interferon gamma but not interleukin 4 or interleukin 10, induction of high concentrations of nitric oxide synthase activity in peripheral blood mononuclear cells, and a drop in the number of peripheral natural killer T cells. Interpretation People can be protected against the erythrocytic stage of malaria by a strong cell-mediated immune response, in the absence of detectable parasite-specific antibodies, suggesting an additional strategy for development of a malaria vaccine.

Human peripheral blood V alpha 24(+) V beta 11(+) NKT cells expand following administration of alpha-galactosylceramide-pulsed dendritic cells

Background and Objectives We have undertaken the first clinical trial involving the administration of alpha-GalactosylCeramine (alpha-GalCer)-pulsed dendritic cells (DCs) to human subjects, to determine safety, optimal dose, optimal administration route and immunological effects. Materials and Methods Subjects (n = 4) with metastatic malignancy received two infusions of alpha-GalCer-pulsed DCs intravenously, and two infusions intradermally. The percentages of Valpha24 Vbeta11 NKT cells in peripheral blood (PB) were determined by three-colour flow cytometry and the PB NKT cell numbers were calculated using the total number of PB lymphocytes/ml determined by automated full-blood counts. Results No serious treatment related adverse events were observed during the study period. Administration of alpha-GalCer-pulsed DCs in vivo can significantly (P < 0.03) increase PB Valpha24(+) Vbeta11(+) NKT cell numbers above pretreatment baseline levels after the transient fall in the NKT numbers within 48 h. Conclusions Administration of alpha-GalCer-pulsed DCs is well tolerated, modulates PB Valpha24(+) Vbeta11(+) NKT cells and may have a role in the therapy of malignancies sensitive to activities of Valpha24(+) Vbeta11(+) NKT cells, or for autoimmune diseases.

Systemic administration of interleukin-1 beta activates select populations of central amygdala afferents

The central nucleus of the amygdala (CeA) is activated robustly by an immune challenge such as the systemic administration of the proinflammatory cytokine interleukin-1beta (IL-1beta). Because IL-1beta is not believed to cross the blood-brain barrier in any significant amount, it is likely that IL-1beta elicits CeA cell recruitment by means of activation of afferents to the CeA. However, although many studies have investigated the origins of afferent inputs to the CeA, we do not know which of these also respond to IL-1beta. Therefore, to identify candidate neurons responsible for the recruitment of CeA cells by an immune challenge, we iontophoretically deposited a retrograde tracer, cholera toxin b-subunit (CTb), into the CeA of rats 7 days before systemic delivery of IL-1beta (1 mug/kg, i.a.). By using combined immunohistochemistry, we then quantified the number of Fos-positive CTb cells in six major regions known to innervate the CeA. These included the medial prefrontal cortex, paraventricular thalamus (PVT), ventral tegmental area, parabrachial nucleus (PB), nucleus tractus solitarius, and ventrolateral medulla. Our results show that after deposit of CTb into the CeA, the majority of double-labeled cells were located in the PB and the PVT, suggesting that CeA cell activation by systemic IL-1beta is likely to arise predominantly from cell bodies located in these regions. These findings may have significant implications in determining the central pathways involved in generating acute central responses to a systemic immune challenge. J. Comp. Neurol. 452:288-296, 2002. (C) 2002 Wiley-Liss, Inc.

??cole Nationale d'Administration Publique: d??velopper les comp??tences des fonctionnaires pour augmenter la capacit?? de L'Etat dans la gestion des politiques publiques

Plus d???une vingtaine d???ann??es d???existence d??di??es ?? la mission de d??velopper les comp??tences des fonctionnaires pour augmenter la capacit?? de l?????tat dans la gestion des politiques publiques fait de l???ENAP un mod??le dans le domaine de la formation. Rattach??e au Minist??re du Plan, du Budget et de la Gestion, l?????cole, d??s sa cr??ation en 1986, a re??ue 245 mille fonctionnaires de tout le pays. En 2007, 26 mille fonctionnaires de l???administration f??d??rale ont attendu un de nos 60 stages offerts.

Brazilian National School of Public Administration

The Brazilian National School of Public Administration (Escola Nacional de Administra????o P??blica ??? ENAP) is a public foundation linked to the Ministry of Planning, Budget and Management. Founded in 1986, its core mission is ???to develop competencies of civil servants in order to enhance government capacity for managing public policies???. To fulfill its mission, a wide program of learning and continued education is offered to public policy managers as well as e-learning and customized courses, in accordance to governmental and institutional strategic objectives. ENAP???s courses are framed according to governmental strategic demands for social inclusion, poverty reduction as well as economic development in order to strengthen the leading South American democracy. The range and diversity of its programs mirrors the challenges of deep changes in the jobs market and the work environment, faced by the current 550,000 federal civil servants and the over 7,000,000 state and municipal civil servants in Brazil, as last counted in 2006.

As políticas da insegurança : da Scuderie Detetive Le Cocq às masmorras do novo Espírito Santo

A presente dissertação tem como objetivo a análise das políticas de segurança pública e justiça criminal no Espírito Santo entre 1989 e 2013, utilizando metodologia historiográfica e observando a distância entre os objetivos oficiais e as consequências práticas. No primeiro capítulo, me concentro na contextualização histórica das políticas criminais, analisando a formação organizacional do sistema punitivo brasileiro. Coloco ênfase, de um lado, no processo de militarização, isto é, a adoção de hierarquia, disciplina e formação militares nas agências de segurança pública, e de outro lado, e nas sucessivas legislações penais aprovadas pelo Congresso Nacional. Tais processos nacionais se refletem no Espírito Santo, onde se difundiram “grupos de extermínio” como a Scuderie Le Cocq, mas não havia política de segurança pública. A primeira surge em meio a grave crise política, entre 1999 e 2002. Mas os seus propósitos são mais avançados com o processo de reforma administrativa após 2003, quando o governo se esforça por impôr modelos de gestão empresariais e parcerias público privadas à administração estadual, incluindo a segurança pública e sistema penitenciário. Com isto, ocorre uma rápida expansão do encarceramento seletivo em condições extremas de superlotação e violência, desenvolvendo uma indústria carcerária. No segundo capítulo, realizo uma análise na qual relaciono informações criminais, penitenciárias, econômicas e demográficas, tanto no contexto do Brasil quanto do Espírito Santo. Constato que a repressão estatal tem “preferência” por homens, negros, jovens e de baixa escolaridade; por crimes de drogas e contra o patrimônio, com a utilização cada vez maior da prisão provisória. No Espírito Santo o encarceramento seletivo cresce em maior velocidade que na média nacional, o que se reflete no perfil da população carcerária, sendo esta ainda mais negra, jovem, de baixa escolaridade e presa por tráfico e drogas e em regime provisório, com frequentes denúncias fundamentadas de torturas, mortes e desaparecimentos forçados entre as populações criminalizadas.

Consciência política e participação cidadã de estudantes de Administração em uma universidade pública federal no Sudeste do Brasil

Em um contexto de ampliação dos lugares públicos participativos no Brasil há de se considerar expectativas de despertar valores sociopolíticos nos estudantes universitários em seu processo de qualificação cidadã e profissional, diante das críticas à formação dos administradores. Portanto, este trabalho visa compreender a dinâmica da consciência política dos estudantes da graduação em administração de uma universidade pública federal no sudeste do Brasil em sua relação com a participação cidadã nos lugares públicos participativos no estado e municípios. Adota-se o modelo analítico de consciência política para a compreensão da participação em ações coletivas de Sandoval (2001) como marco teórico, associado à literatura sobre participação cidadã. Trata-se de uma pesquisa qualitativa, cujos dados foram coletados através de documentos, aplicação de 30 questionários e 17 entrevistas semiestruturadas, com 30 estudantes universitários da graduação em administração matriculados em 2014/1. Os dados foram submetidos à análise de conteúdo (BARDIN, 2004). Os resultados revelam 12 estudantes que não participam nos lugares públicos participativos e 18 estudantes que participam em pelo menos um destes lugares. O interesse em exercer a cidadania, melhorar as políticas públicas, gostar de implicar-se com os assuntos públicos e defender seus interesses em circunstâncias de conflito são as justificativas citadas pelos que participam. Evidenciam-se nos estudantes com participação mais ativa, crenças, valores e expectativas societais, articuladas à eficácia política, identidade coletiva, interesses antagônicos, sentimentos de justiça e injustiça, favorecendo a vontade de agir coletivamente, devido à percepção de conexão de seus interesses com as metas e ações coletivas dos movimentos que se envolvem. Os estudantes que não participam desconfiam dos lugares públicos participativos e demonstram desinteresse pelos assuntos públicos, embora apontem um desconforto em não participar. Suas crenças, valores e expectativas societais, associadas aos sentimentos de ineficácia política dificultam o desenvolvimento da consciência política. Conclui-se que estes estudantes possuem uma consciência política de senso comum, demonstrando valores sociais e políticos inerentes aos modismos presentes na vida cotidiana das pessoas. Já os estudantes com participação mais ativa apresentam uma consciência política de conflito, motivando-os à participação nos lugares avaliados como eficazes às suas proposições. Entretanto, o Centro Acadêmico Livre de Administração Honestino Guimarães (CALAD), principal lugar de representação e participação dos interesses dos estudantes no curso, encontra-se sem direção e participação nas instâncias institucionalizadas na universidade.