Regulation of Placental Leptin Expression by Cyclic Adenosine 5 '-Monophosphate Involves Cross Talk between Protein Kinase A and Mitogen-Activated Protein Kinase Signaling Pathways

Leptin, a 16-kDa protein mainly produced by adipose tissue, has been involved in the control of energy balance through its hypothalamic receptor. However, pleiotropic effects of leptin have been identified in reproduction and pregnancy, particularly in placenta, where it was found to be expressed. In the current study, we examined the effect of cAMP in the regulation of leptin expression in trophoblastic cells. We found that dibutyryl cAMP [(Bu)(2)cAMP], a cAMP analog, showed an inducing effect on endogenous leptin expression in BeWo and JEG-3 cell lines when analyzed by Western blot analysis and quantitative RT-PCR. Maximal effect was achieved at 100 microM. Leptin promoter activity was also stimulated, evaluated by transient transfection with a reporter plasmid construction. Similar results were obtained with human term placental explants, thus indicating physiological relevance. Because cAMP usually exerts its actions through activation of protein kinase A (PKA) signaling, this pathway was analyzed. We found that cAMP response element-binding protein (CREB) phosphorylation was significantly increased with (Bu)(2)cAMP treatment. Furthermore, cotransfection with the catalytic subunit of PKA and/or the transcription factor CREB caused a significant stimulation on leptin promoter activity. On the other hand, the cotransfection with a dominant negative mutant of the regulatory subunit of PKA inhibited leptin promoter activity. We determined that cAMP effect could be blocked by pharmacologic inhibition of PKA or adenylyl ciclase in BeWo cells and in human placental explants. Thereafter, we decided to investigate the involvement of the MAPK/ERK signaling pathway in the cAMP effect on leptin induction. We found that 50 microm PD98059, a MAPK kinase inhibitor, partially blocked leptin induction by cAMP, measured both by Western blot analysis and reporter transient transfection assay. Moreover, ERK 1/2 phosphorylation was significantly increased with (Bu)(2)cAMP treatment, and this effect was dose dependent. Finally, we observed that 50 microm PD98059 inhibited cAMP-dependent phosphorylation of CREB in placental explants. In summary, we provide some evidence suggesting that cAMP induces leptin expression in placental cells and that this effect seems to be mediated by a cross talk between PKA and MAPK signaling pathways.

Up-regulation of placental leptin by human chorionic gonadotropin.

Leptin, the 16,000 molecular weight protein product of the obese gene, was originally considered as an adipocyte-derived signaling molecule for the central control of metabolism. However, leptin has been suggested to be involved in other functions during pregnancy, particularly in placenta, in which it was found to be expressed. In the present work, we have found that recombinant human chorionic gonadotropin (hCG) added to BeWo choriocarcinoma cell line showed a stimulatory effect on endogenous leptin expression, when analyzed by Western blot. This effect was time and dose dependent. Maximal effect was achieved at hCG 100 IU/ml. Moreover, hCG treatment enhanced leptin promoter activity up to 12.9 times, evaluated by transient transfection with a plasmid construction containing different promoter regions and the reporter gene luciferase. This effect was dose dependent and evidenced with all the promoter regions analyzed, regardless of length. Similar results were obtained with placental explants, thus indicating physiological relevance. Because hCG signal transduction usually involves cAMP signaling, this pathway was analyzed. Contrarily, we found that dibutyryl cAMP counteracted hCG effect on leptin expression. Furthermore, cotransfection with the catalytic subunit of PKA and/or the transcription factor cAMP response element binding protein repressed leptin expression. Thereafter we determined that hCG effect could be partially blocked by pharmacologic inhibition of MAPK pathway with 50 microM PD98059 but not by the inhibition of the phosphatidylinositol 3-kinase pathway with 0.1 microm wortmannin. Moreover, hCG treatment promoted MAPK kinase and ERK1/ERK2 phosphorylation in placental cells. Finally, cotransfection with a dominant-negative mutant of MAPK blocked the hCG-mediated activation of leptin expression. In conclusion, we provide some evidence suggesting that hCG induces leptin expression in trophoblastic cells probably involving the MAPK signal transduction pathway.

International recommendations on the diagnosis and treatment of patients with acquired hemophilia A.

Acquired hemophilia A (AHA) is a rare bleeding disorder characterized by autoantibodies directed against circulating coagulation factor (F) VIII. Typically, patients with no prior history of a bleeding disorder present with spontaneous bleeding and an isolated prolonged aPTT. AHA may, however, present without any bleeding symptoms, therefore an isolated prolonged aPTT should always be investigated further irrespective of the clinical findings. Control of acute bleeding is the first priority, and we recommend first-line therapy with bypassing agents such as recombinant activated FVII or activated prothrombin complex concentrate. Once the diagnosis has been achieved, immediate autoantibody eradication to reduce subsequent bleeding risk should be performed. We recommend initial treatment with corticosteroids or combination therapy with corticosteroids and cyclophosphamide and suggest second-line therapy with rituximab if first-line therapy fails or is contraindicated. In contrast to congenital hemophilia, no comparative studies exist to support treatment recommendations for patients with AHA, therefore treatment guidance must rely on the expertise and clinical experience of specialists in the field. The aim of this document is to provide a set of international practice guidelines based on our collective clinical experience in treating patients with AHA and contribute to improved care for this patient group.

Are the Policy Preferences of Relatively Poor Citizens Under-represented in the Swiss Parliament?

The principle of equal political representation can be undermined by differences in economic resources among citizens. Poor citizens are likely to hold policy preferences that differ from those of richer citizens. At the same time, their lack of resources can have as a consequence that these preferences are not taken into consideration by their representatives. Focusing on the case of the Swiss Parliament and using survey data on the opinions of citizens and MPs in the 2007-2011 legislature, this study investigates whether the income of citizens systematically affects the proximity of their policy preferences with stances of their representatives. It demonstrates that on economic issues MPs hold preferences that are generally less in favour of the state's intervention in the economy than the median citizen and that relatively poor citizens are less well represented as compared to citizens with high incomes. This remains true when taking into account only the opinions of the most knowledgeable citizens among these groups as well as when the focus is only on those who turned out to vote.

Rede de Segurança Alimentar

O Ministério do Ambiente e Agricultura, através da DGPOG/DSSA, pretende implementar uma rede de Segurança Alimentar, no quadro da execução do Programa Nacional de Segurança Alimentar, 2007-2011 com vista a criar um quadro de concertação e articulação de todos os sectores que de uma forma ou de outra intervêm nesse domínio. Neste contexto, foi solicitado à FAO assistência técnica, para elaboração de um projecto para a operacionalização dos mecanismos de implementação do PNSA.

“Triple discriminación mujer, negra y lesbiana”

Manual de buenas prácticas y responsabilidades estatales y de las agencias de Cooperación Internacional con las personas Lesbianas, Gais, Bisexuales y Transexuales1 en África Esta comunicación girará en torno al trabajo que realiza Kasha Nabagesera, presidenta de Freedom and Roam Uganda, donde la homosexualidad es ilegal y actualmente se encuentra en revisión para ser cambiada por la pena de muerte; Alice Nkom, presidenta de la Association pour la Défense de l’Homosexualité – Camerún, donde la homosexualidad es ilegal con cárcel de hasta 7 años y Claudia Rodrígues, directora, del Instituto Cabo-verdiano para a Igualdade e Equidade do Género, representa la cara amable de África hacia la “Homoafectividade”. “Triple discriminación: mujer, negra y lesbiana” formó parte de la I Conferencia de Derechos Humanos de las personas LGBT en África organizada por la Fundación Triángulo el 8 y 9 de abril de 2010 en Tenerife - España. Con esta ponencia pretendemos presentar el Manual de buenas prácticas y responsabilidades estatales y de las agencias de Cooperación Internacional con las personas Lesbianas, Gais, Bisexuales y Transexuales (LGBT) en África.

Los efectos de "El Niño" 1982-83 y los mecanismos internacionales para la investigación

Durante 1982 -83 se presentó, frente a las costas sudamericanas del Pacífico, el fenómeno de «El Niño» (EN) catalogado como el más intenso del siglo. Inesperadamente, el régimen de temperaturas superficiales del mar se incrementó rápidamente a partir de octubre de 1982, superando más de 7 ºC por encima del promedio. Las precipitaciones normalmente altas en el Ecuador, sobrepasaron al promedio anual en más de 600 % y mucho más en las zonas semiáridas del norte del Perú. Las perturbaciones climáticas y oceánicas se manifestaron durante 12meses por lo menos; las lluvias se propagaron hasta la zona central del Perú y los cambios oceánicos a todo el Pacífico Sudeste. Las reuniones científicas realizadas en la región del Pacífico Sudeste y fuera de esta, dieron a conocer notables cambios tanto físicos como biológicos en toda la Cuenca del Pacífico. Estas alteraciones afectaron en el mar la actividad pesquera y en el continente la agricultura, infraestructura vial, industrial y viviendas, así como la educación y la salud. Los gobiernos de Ecuador y Perú se vieron precisados a declarar en emergencia las áreas afectadas. Los daños que se consignan en el presente informe se consideran sólo parciales por tener como base evaluaciones realizadas hasta febrero de 1983. Las lluvias continuaron aún con mayor fuerza en los meses siguientes. Los gobiernos y las instituciones de la región reaccionaron intensificando la vigilancia de los cambios climáticos y oceánicos en relación con los recursos. La Comisión Permanente del Pacífico Sur (CPPS), coor dinó las actividades del Grupo ERFEN y organizó reuniones científicas con apoyo de la COI-UNESCO y la OMM. Estos organismos así como la FAO propiciaron y estimularon por su parte programas globales. A pesar de lo anterior, la importancia socio-económica de EN requiere de una mayor coordinación y cooperación internacional. La meta de los programas es lograr una adecuada predicción de EN.

Gestão Orçamental da Câmara Municípal da Praia

O presente trabalho que se intitula “Gestão Orçamental da Câmara Municípal da Praia ( 2007-2011) ”, enquadra-se no âmbito do curso de licenciatura em Económia e Gestão, variante Administração e Controlo Financeiro, realizado pela Universidade Jean Piaget de Cabo Verde. Perante a fraca arrecadação das receitas por parte da Câmara Municipal da Praia, bem como a mobilização dos recursos financeiros para a realização dos investimentos e, sendo assim, a prossecução dos objectivos preconizados, nomeadamente a nível sócioeconómico e ambiental, há que se fazer uma gestão rigorosa e transparente do orçamento, primando-se pela legalidade, o que nem sempre é possível, tendo em consideração aos condiconalismos de várias ordens, sobretudo a nível político, técnico, o que associado a falta dos recursos humanos qualificados, para o efeito, acaba-se por agravar a situção, a esse respeito.Este trabalho tem, entre outros objectivos, como objectivo geral analisar a gestão orçamental da Câmara Municipal da Praia, de forma a compreender o processo de planeamento, programação, orçamentação e execução do orçamento, conhecer o processo orçamental das receitas e das despesas e sugerir medidas de políticas e estratégias que contribuam para uma melhor gestão orçamental dessa instituição. Para a realização deste trabalho utilizou-se o método exploratório, com recurso ao estudo documental, sobretudo pesquisas bibliograficas, legislações, revistas, uso de sites sobre a gestão orçamental e outras fontes de informação que servem de suporte para análise e resposta as perguntas de partidas formuladas. Ainda, fez-se a análise SWOT da dimensão económica e financeiro sobre a gestão orçamental da Câmara Municipal da Praia. Com a realização do trabalho concluiu-se que o orçamento do município é indispensável para o desenvolvimento local e que os eventuais problemas socioeconómicos, políticos, sociais e ambientais são frutos da má gestão municipais e da interligação com o Governo.

L’Impacte real de l’Enfocament Basat en els Drets Humans com a eina per a la transformació político-social d’una regió

Aquest estudi pretén donar resposta a la hipòtesi de si l’enfocament basat en drets humans (EBDH) suposa un nou paradigma de treball dins el sistema de cooperació internacional per al desenvolupament per a la veritable transformació socio-política d’una regió. L’estudi en cap cas se centra només en els drets humans, sinó en l’EBDH com una metodologia de treball dins l’àmbit de la cooperació internacional al desenvolupament la qual vol donar resposta a l’objectiu de reduir la pobresa i combatre la injustícia social.

Impacto de la ayuda oficial al desarrollo de donantes de OCDE-CAD en el proceso de reconciliación nacional en Perú (2000-2010)

La cooperación internacional en el Perú ha tenido un rol importante durante la reconciliación nacional y transición democrática en el Perú luego del terrorismo. El presente trabajo se centrará en la denominada ayuda oficial al desarrollo (AOD) de fuentes bilaterales del 2000 al 2010, pues es la que ha tenido un protagonismo decisivo en el país, sobre todo en las políticas relativas a construcción de paz (peace building) y reconstrucción democrática y porque existe información y registros más fiables tales como los de la Organización para la Cooperación y el Desarrollo Económico (OCDE) así como de las agencias gubernamentales.

Estudio termodinámico sobre la mineralogénesis de la Galena en la mina de Cierco (Alta Ribagorza)

Se efectúa un estudio de la mineralogénesis de la galena en la mina de Cierco (Alta Riborgaza). Se determina a partir de cálculos termodinamicos la solubilidad de la galena en una solución hidrotermal a 150ºC y 3 molal de NaCl y se estudian 10s efectos de los diferentes posibles agentes precipitantes. A partir de las mineralizaciones que acompañan a la galena, del conocimiento que se dispone de las inclusiones presentes en las mineralizaciones se efectúan posibles hipótesis sobre la formación del yacimiento.

Evaluation du projet EVITA: rapport final

Le projet EVITA (EValuation Indication, Traitement ambulatoire, Accompagnement) s'inscrit dans le Plan cantonal d'action Alcool (2007-2012), lui-même en conformité avec le Plan national Alcool (2007-2011). Ce projet est un mandat du Service de la santé publique qui a pour objectif la mise en oeuvre et l'évaluation d'un dispositif cantonal d'indication et de suivi (DCIS) constituant une porte d'entrée unique. Le DCIS est constitué d'un partenariat entre la Fondation vaudoise contre l'alcoolisme (FVA) et le Centre de traitement en alcoologie (CTA) du CHUV. C'est l'Unité d'évaluation de programmes de prévention (UEPP) de l'Institut universitaire de médecine sociale et préventive (IUMSP) qui a été chargée par le CTA, mandant, de l'évaluation du projet EVITA et qui en a rédigé le protocole. [Introduction, p. 5]

Irradiacions tropicals dins la vegetació nitròfila mediterrània

Tropical irradiations into Mediterranean nitrophilous vegetation. Irradiations of pantropical Ruderali-Manihotetea reach Mediterranean countries. Hygronitrophilous Ecliption prostratae, trodden and disturbed ground-colonizing Eleitsinion indicae and suburban Lycio-Ipomoeion curtain communities are specially examined.

Huellas de la escritura materna en el español escrito como L2

Siguiendo los Nuevos Estudios de Literacidad y utilizando técnicas etnográficas (observación, entrevistas), criticamos varios aspectos de la concepción cognitiva de la “lectura en idioma extranjero” y proponemos una alternativa más sociocultural, que incorpora las particularidades reseñadas, que ofrece una visión más realista y completa y que pone el acento en el alfabetismo crítico. A partir de entrevistas a hablantes competentes del español como L2, que fueron alfabetizados en una lengua materna tipológicamente muy diferente y con un sistema de escritura distinto, exploramos el efecto que tienen las prácticas literarias escolares, en varias culturas, en el aprendizaje del español como segunda lengua.