BOLETIM INFORMATIVO ABRASCO

Vice-presidentes da ABRASCO participam de reunião promovida pelo Conselho Federal de Medicina Os Vice-Presidentes da ABRASCO, Luis Eugenio Portela e Elias Rassi, participaram de um encontro promovido pelo Conselho Federal de Medicina (CFM), no dia 13 de abril, que reuniu parlamentares, governadores de Estado, secretários de saúde (estaduais e de capitais) e líderes de entidades nacionais com representantes dos Conselhos Federal e Regionais de Medicina. A reunião aconteceu em Brasília e promoveu a discussão em torno da agenda prioritária para a saúde e o exercício profissional, fortalecendo laços e firmando o compromisso de desenvolver ações conjuntas em benefício da sociedade. Para Luis Eugenio "os encontros com parlamentares, governadores e secretários da saúde médicos, organizados pelo CFM servem para fortalecer posições que se aproximam dos temas da Agenda Estratégica que o Movimento da Reforma Sanitária tem discutido: aumentar os recursos para o SUS, modernizar a gestão, valorizar o trabalho profissional, implantar um modelo de atenção baseado na integralidade". Veja o vídeo do encontro clicando aqui.

Seminário Nacional sobre Escassez, Provimento e Fixação de Profissionais em Áreas Remotas e de Maior Vulnerabilidade A vice-presidente da ABRASCO, Lígia Bahia, participou do Seminário Nacional sobre Escassez, Provimento e Fixação de Profissionais da Saúde em Áreas Remotas e de Maior Vulnerabilidade onde coordenou o debate sobre "Necessidades e Estratégias de Provimento e Fixação de Profissionais no SUS". O evento foi uma realização do Ministério da Saúde em parceria com o Conselho Nacional dos Secretários de Saúde (CONASS), Conselho Nacional das Secretarias Municipais de Saúde (CONASEMS) e a Organização Pan-Americana de Saúde (OPAS). O encontro teve como objetivo reafirmar o alinhamento das ações nacionais já implementadas com as diretrizes da OMS, apontar a ampliação das ações e da articulação entre os atores do processo para o enfrentamento do problema para avaliar e estruturar a proposição da política do país para o enfrentamento da escassez, provimento e fixação de profissionais do SUS em áreas remotas e de maior vulnerabilidade. Participam do seminário representantes dos Ministérios da Educação, Ciência e Tecnologia, Defesa, Trabalho e Casa Civil, além de gestores do SUS nos âmbitos federal, estadual e municipal; instituições de ensino, pesquisadores, técnicos, entidades representativas dos trabalhadores e parlamentares com atuação na área de saúde. Veja mais detalhes sobre o encontro aqui.

I Ciclo de Debates: o SUS que temos, o SUS que queremos A vice-presidente da ABRASCO, Lígia Bahia, participou do "I Ciclo de Debates: o SUS que temos, o SUS que queremos", no dia 12 de abril, na Assembléia Legislativa do Paraná. O encontro contou com as presenças do ex ministro da Saúde José Gomes Temporão e do consultor em saúde pública Gilberto Scarazatti. Proposto pelos deputados Gilberto Martin (PMDB) e Dr. Batista (PMN), o evento foi promovido pela Frente Parlamentar em Defesa do SUS e pela Comissão de Saúde da Assembléia Legislativa. Mais informações no aqui.

VIII Congresso Brasileiro de Epidemiologia: prazo de envio de resumos é prorrogado! O prazo de envio de resumos para o VIII Congresso Brasileiro de Epidemiologia foi prorrogado até o dia 30 de abril. O Congresso, promovido pela Comissão de Epidemiologia da ABRASCO, será realizado de 12 a 16 de novembro de 2011, em São Paulo. Esta edição terá como tema central o debate sobre a Epidemiologia e seu papel na definição de políticas públicas, articulado que está ao conjunto das demais disciplinas do campo da Saúde Coletiva. O primeiro prazo para inscrição com desconto vence no dia 31 de dezembro. Mais informações sobre o evento estão disponíveis no site: www.epi2011.com.br.

Da Atenção Básica à Hospitalização: Doenças, Agravos e Cuidado de Saúde A Revista Ciência & Saúde Coletiva lançará seu primeiro suplemento especial do ano durante o V Congresso Brasileiro de Ciências Sociais e Humanas em Saúde, no dia 19 de abril, das 17h30 às 18h, na Faculdade de Educação da USP. O novo exemplar tem como tema "Da Atenção Básica à Hospitalização: Doenças, Agravos e Cuidado de Saúde" e reúne 100 artigos sobre sete tópicos: (1) aspectos éticos e bioéticos relacionados à reforma sanitária, ao mercado dos laboratórios clínicos e planos de saúde, à inclusão no sistema de saúde de pessoas com algum tipo de deficiência e aos dilemas do fim da vida; (2) atenção básica, levando-se em conta os usuários, os profissionais e a multiprofissionalidade; (3) a questão hospitalar enquanto instituição, custos, qualidade dos serviços, humanização, satisfação dos usuários e outros; (4) sistemas de informação em saúde, quanto à qualidade, os serviços e ao uso dos dados para a gestão; (5) estudos epidemiológicos e de gestão sobre mortalidade, morbidade e problemas relevantes como a proliferação da dengue, diabetes, hipertensão arterial e vários outros tipos de agravos, (6) consumo de medicamentos; (7) educação e saúde e a contribuição dos diferentes profissionais que compõem a área. Este número pode ser considerado como uma amostra do que vem sendo produzido pelos pesquisadores e profissionais da saúde coletiva e constitui mais um esforço da ABRASCO para entregar aos leitores uma reflexão variada, ampliada e aprofundada sobre a área, respeitando o pensamento individual e coletivo frente aos dados e desafios do setor. Veja o sumário da Revista clicando aqui.

Publicações e oportunidades Clique nos links a seguir e confira as publicações e oportunidades da semana.

Enzyme Crucial to DNA Replication May Provide Potent Anti-Cancer Drug Target

ScienceDaily (Apr. 15, 2011) — An enzyme essential for DNA replication and repair in humans works in a way that might be exploited as anti-cancer therapy, say researchers at The Scripps Research Institute and Lawrence Berkeley National Laboratory.

During DNA replication of the lagging strand, numerous Okazaki fragments must be joined. The newer fragment ends in a short flap call the 3’ overhang, while the previous fragment leaves a long 5’ flap after its primer is removed. The junction opens when the template strand is bent 100 degrees. FEN1 grasps the DNA at the bend, threads the flap through an archway, and trims the flap to match the overhang.

"This work represents a seminal advance in the understanding of FEN1," said team leader John Tainer, professor and member of the Skaggs Institute for Chemical Biology at Scripps Research and senior scientist at Lawrence Berkeley National Lab. "The research produced very accurate structures showing DNA before and after being cut by FEN1 activity, providing a basis for understanding a whole superfamily of enzymes that must cut specific DNA structures in order for DNA to be replicated and repaired."The research, published in the April 15, 2011 issue of the journal Cell,focused on a member of a group of enzymes called flap endonucleases, which are essential to the life of a cell. The findings show new, clearly defined crystal structures of the enzyme FEN1 in action -- demonstrating it functions in a way opposite to accepted dogma.

This superfamily includes important targets for the development of new cancer interventions, Tainer added. Many cancers show high levels of FEN1 expression, which in some cases is correlated to tumor aggression. For these cases, FEN1-specific inhibitors may have chemotherapeutic potential.

"A better understanding of FEN1 structure and function may have long-term positive benefits to human health," noted co-author Andy Arvai, a scientific associate at Scripps Research.

Working rapidly with exquisite precision

In order for DNA to replicate, it has to unwind its double helix, which is formed out of two strands of amino acids coiled together. This unwinding is done by a replication fork whereby the two strands are separated. These strands, which form two branching prongs of the replication fork, serves as a template for production of a new complementary strand.

That task is fairly straightforward on what is known as the "leading" of the two strands. The replication fork moves along from the so-called 3' (three prime) end to the 5' (five prime) end, and DNA polymerase synthesizes a 5' to 3' complementary strand.

But because the two strands are anti-parallel, meaning they are oriented in opposite directions, the work of DNA polymerase, which can only work in the 5' to 3' direction, is more difficult on the so-called lagging strand. This strand needs to be replicated in pieces, which are known as Okazaki fragments, located near the replication fork. These fragments include a "primer," a strand of RNA that serves as a starting point for DNA synthesis.

This is where FEN1 comes in -- it removes that RNA primer on the 5' flap, which occurs every 100 base pairs or so on the lagging strand, said Tainer. It's an enormous job that has to be done rapidly and accurately in order to glue the ends of replicated DNA on the lagging strand together to eventually provide an intact chromosome. "To replicate one DNA double helix in one cell you have to cut off a 5' flap so that you don't have one base pair too many or one base pair too few, and you have to do this accurately with 50 million Okazaki primers in each cell cycle," Tainer said. "It has always been a mystery as to how FEN1 can precisely cut this flap so efficiently and so rapidly. It's an amazing, efficient molecular machine for precisely cutting DNA."

To determine what FEN1 looked like in action, Arvai led the difficult but ultimately successful effort to grow crystals of the human FEN1 protein bound to DNA. The team then used X-ray crystallography to determine the atomic structure of the complex. Using Lawrence Berkeley National Laboratory's Advanced Light Source beamline, called SIBYLS, the scientists solved three different crystal structures.

The end result was a highly detailed and accurate model showing the structures of DNA before and after being cut by FEN1.

Earlier crystal structures suggested that FEN1 first grabs onto the flap of the 5' single stranded DNA, slides down to the joint where DNA is duplicated, and cuts and patches the primer there. But the new study found that, in fact, FEN1 binds, bends, frays, and then cuts the DNA.

"It binds duplex DNA, bends it into a single-stranded DNA right at the flap, flips out two base pairs, and cuts between them," said Tainer. "This gives FEN1 very precise control -- a sophistication we had not expected."

Clues to cancer control

Researchers know that mutations in FEN1 can predispose humans to cancer growth because errors in flap removal can create unstable DNA that promotes cell growth and division. And studies in mice have shown that when one of two inherited FEN1 genes are knocked out, the mice are predisposed to cancer development if their DNA is damaged.

While other DNA repair systems can help compensate for FEN1 mistakes, or for missing FEN1 activity, "you need a lot of FEN1 for DNA repair and replication to work properly," Tainer said.

This suggests that, in tumors already missing one set of repair proteins, selectively inhibiting the function of FEN1 in rapidly replicating cells may prove to be an effective anti-cancer therapy. "The Achilles heel of cancer cells is defective DNA repair pathways," said Tainer, "because that makes them more sensitive to traditional therapies, such as chemotherapy and radiation. If cancer can't repair the damage these therapies do to tumors, they will die."

This is the paradox of DNA repair: while a defect in DNA repair can cause cancer, knocking out a number of backup repair systems may make tumors vulnerable to anti-cancer therapies.

"My hope is that our finding of how FEN1 works mechanistically might provide a foundation for a next-generation cancer drug," said Tainer. "We need to cut as many lifelines as possible in cancer cells in order to provide an effective treatment."

Studies of Marine Animals Aim to Help Prevent Rejection of Transplanted Organs

ScienceDaily (Apr. 15, 2011) — Studies of the small sea squirt may ultimately help solve the problem of rejection of organ and bone marrow transplants in humans, according to scientists at UC Santa Barbara.

Botryllus schlosseri is a type of sea squirt.

An average of 20 registered patients die every day waiting for transplants, due to the shortage of matching donor organs. More than 110,000 people are currently waiting for organ transplants in the U.S. alone. Currently, only one in 20,000 donors are a match for a patient waiting for a transplant.

These grim statistics drive scientists like Anthony W. De Tomaso, assistant professor of biology at UCSB, to delve into the cellular biology of immune responses. His studies of the sea squirt shed light on the complicated issue of organ rejection. The latest results are published online April 14 in the journal Immunity.

De Tomaso hopes to understand how it might be possible to "tune" the body's immune response in order to dial down the rejection of a donated organ. Studying cellular responses in simple organisms may also eventually help with autoimmune diseases -- those in which the body mistakenly attacks itself.

"Right now, when you get a transplant, you're usually on immunosuppressives your whole life," said De Tomaso. "And that's like sort of kicking your immune system in the teeth. What if we could raise the threshold of when you would respond, instead of just shutting the whole system off?"

De Tomaso and his research team study Botryllus schlosseri, a type of sea squirt. This small organism -- known as a tunicate because of its covering, or "tunic" -- is a modern day descendant of the vertebrate ancestor, the group to which we belong. Tunicates begin life as swimming tadpoles with primitive backbones, nerves, and musculature that are similar to all vertebrates, but soon transform into stationary creatures. Tunicates latch onto intertidal surfaces and look like flat flowers -- with each "petal" being a separate, but genetically identical, body.

De Tomaso focuses on what happens when one sea squirt lands next to another. In this case, cells in the sea squirt's fingerlike edges, or "ampullae," recognize the neighboring sea squirt as "self" or "non-self." When the other sea squirt is related, then the two colonies fuse; otherwise, they reject each other. De Tomaso was involved in identifying the gene controlling the choice between fusion and rejection in the sea squirt when he was a postdoctoral fellow at Stanford University

In his current research, De Tomaso studies how the signals on the surface of the sea squirt's cells get translated inside the circuitry of the cell, where the final decision about acceptance or rejection is made. "In the case of Botryllus, what we found is that we have the same kind of integration that goes on in humans, but instead of having a multiple, very complex set of inputs coming in, we only have two," said DeTomaso. "We have also found that we can manipulate each one independently, so we know that somehow they are put together and the two inputs are integrated, and a decision is made about how to respond."

De Tomaso explained that he decided to work on Botryllusbecause it has a unique way to answer a very complicated question. He hopes to understand the process of rejection or acceptance. "If we could manipulate that process," said Tomaso, "then we could basically teach the immune system to simply ignore certain things. We could say, 'Just don't respond to this. We're going to transfer this bone marrow, just don't kill this bone marrow.' Bone marrow could get in and start making new blood, and it would be fine. To me, that's the most exciting thing long-term for the work."

Tanya R. McKitrick is the first author on the paper. She works in De Tomaso's lab at UCSB and also at Stanford University. Other co-authors are Christina C. Muscat, Stanford University; James D. Pierce, UCSB; and Deepta Bhattacharya, Washington University School of Medicine.