Seminário de Direito Sanitário será transmitido em tempo real

Evento realizado pela FIOCRUZ Brasília, nos dias 22 e 23 de março, será transmitido pelo site do Interlegis

O Seminário de Direito Sanitário: O Direito à Saúde na Produção Legislativa, realizado nos próximos dias 22 e 23, tem como objetivo promover o debate de questões polêmicas que envolvem o setor da saúde e o Poder Legislativo, a partir da discussão de temas importantes para o sistema público de saúde dentro do cenário político brasileiro. O evento, promovido pelo Programa de Direito Sanitário da FIOCRUZ Brasília (Prodisa), em parceria com a Consultoria Legislativa do Senado Federal, será transmitido em tempo real no site do Interlegis, programa de interação legislativa do Senado Federal.

A coordenadora do Seminário e do Programa de Direito Sanitário da FIOCRUZ Brasília, Maria Célia Delduque, fala sobre o foco principal do Seminário. “O estudo do Direito Sanitário é muito amplo, envolve assuntos como a produção legislativa no direito à saúde, que é o tema deste seminário, como por exemplo, o que o parlamento tem produzido em relação a isso”. E acrescenta. “Nosso objetivo é despertar nos parlamentares a importância do SUS e dos projetos que estão aguardando regulamentação, além de incentivar nos participante s o estudo do Direito Sanitário”.

A programação conta com o debate de temas como a inflação legislativa no campo da saúde, de projetos que tratam da responsabilidade sanitária e da regulamentação da Emenda Constitucional nº 29, que prevê maiores recursos para o Sistema Único de Saúde (SUS). Entre outros assuntos, o Seminário abordará ainda a regulamentação da publicidade de produtos como o tabaco, bebidas e alimentos, e outros projetos de lei que tramitam no Congresso Nacional na área da saúde.

O consultor legislativo do Senado Federal e também organizador do evento, Luiz Carlos Romero, fará uma apresentação sobre o tema A concretização do Direito à Saúde no Brasil: uma análise da legislação sobre doenças e agravos específicos. Segundo Romero, há atualmente um excesso de produção de leis específicas, relacionadas a doenças e pequenos grupos. “Os grandes temas polêmicos não estão conseguindo prosperar, como a Regulamentação da Emenda nº 29, atualmente parada na Câmara, que reserva o percentual de certos tributos para financiar a saúde, tendo em vista a enxurrada de leis específicas”, afirma. “Hoje verifica-se que o principal iniciador do processo legislativo é o Poder Executivo, e não o Legislativo, no que se refere às demandas de saúde”, complementa.

Romero também destacou que a propaganda de bebidas é muito mal regulamentada no Brasil. “Dados da Organização Mundial da Saúde (OMS) mostram que o álcool, por exemplo, é um problema de saúde pública que, em relação aos custos para o sistema de saúde, resulta em um impacto maior que a AIDS, os acidentes de trânsito e a tuberculose. Um jeito de diminuir estes custos é diminuir o consumo, e a propaganda é um dos fatores que mais estimula o uso da bebida”, afirma.

OBSERVATÓRIO DA SAÚDE NO LEGISLATIVO — No primeiro dia do evento, será realizado o lançamento do site Observatório Permanente da Saúde no Legislativo, que permitirá, a qualquer pessoa, acompanhar as leis sobre saúde que tramitam no Congresso Nacional. “O Observatório é uma resposta a uma provocação iniciada em 2005, no Simpósio sobre Política Nacional de Saúde, que reuniu várias instituições de saúde. Na ocasião, verificou-se a necessidade de um instrumento para que o cidadão pudesse acompanhar a produção legislativa em saúde”, conta Maria Célia Delduque.

PARCERIAS – “A saúde é um direito de todos e dever do Estado. É estratégico levar estas discussões para dentro Senado Federal, a fim de provocar uma reflexão no corpo político do país, afinal, tudo que acontece dentro do Senado é observado pelo país inteiro”, diz a coordenadora do Prodisa, sobre a realização do evento. “A parceria entre o Senado Federal e a FIOCRUZ Brasília tem possibilitado a capacitação dos consultores da Câmara e do Senado, a criação de uma ferramenta como o Observatório Permanente da Saúde no Legislativo e a realização de eventos como o Seminário de Direito Sanitário”, complementa Romero, sobre a parceria entre as duas instituições.

Molécula sintética detecta Alzheimer antes que sintomas apareçam

Moléculas sintéticas

Cientistas desenvolveram uma nova técnica capaz de diagnosticar a doença de Alzheimer a partir de amostras de sangue muito antes de os sintomas aparecerem.

A técnica, ainda em estágio preliminar, utiliza moléculas sintéticas para procurar e identificar anticorpos específicos da doença.

Segundo os pesquisadores, o conceito também poderá ser usado no desenvolvimento de biomarcadores específicos para uma série de outras doenças difíceis de diagnosticar, incluindo o Mal de Parkinson e doenças ligadas ao sistema imunológico, como a esclerose múltipla e o lúpus.

Biomarcadores de anticorpos

"Um dos grandes desafios no tratamento de pacientes com Alzheimer é que, uma vez que os sintomas aparecem, é tarde demais. Você não consegue 'destocar' o sino," afirma o Dr. Dwight German, da Universidade Southwestern, nos Estados Unidos.

Se pudermos encontrar uma maneira de detectar a doença em seus estágios iniciais - antes que o comprometimento cognitivo comece - poderíamos ser capazes de estacioná-la com o desenvolvimento de novas estratégias de tratamento."

Como os pacientes com doença de Alzheimer apresentam uma ativação dosistema imunológico e neurodegeneração em várias regiões cerebrais, os cientistas levantaram a hipótese de que pode haver inúmeros anticorpos no soro dos pacientes afetados que são específicos para a doença e que podem servir como biomarcadores.

Biomarcadores de anticorpos têm sido tradicionalmente descobertos usando antígenos - substâncias, como a proteína de um vírus ou bactéria que desencadeia uma resposta imune.

O problema é identificar previamente um anticorpo sem antes saber o antígeno que desencadeia a sua produção.

Peptoides

A novidade do novo estudo está em desafiar a sabedoria convencional e usar moléculas sintéticas (peptoides), em vez de antígenos, para detectar os sinais da doença em amostras de sangue dos pacientes.

Estes peptoides têm várias vantagens: eles podem ser modificados facilmente e podem ser produzidos rapidamente em quantidades relativamente grandes a custos muito baixos.

Os pesquisadores usaram uma biblioteca de vários milhares de peptoides para rastrear amostras de soro de camundongos com sintomas de esclerose múltipla, bem como de camundongos sadios.

Os peptoides que capturaram mais anticorpos das amostras de sangue dos animais foram identificados como agentes potenciais para a captura de moléculas úteis para diagnóstico.

Marco

Os pesquisadores então fizeram o mesmo com amostras de soro de seis pacientes com Alzheimer, seis pacientes com Parkinson e seis pacientes saudáveis.

Foram identificados três peptoides que capturaram seis vezes mais anticorpos nos pacientes com Alzheimer do que no grupo controle saudável ou nos pacientes com Mal de Parkinson.

Em um estudo adicional com 16 indivíduos saudáveis e 10 portadores de Alzheimer em estágio muito precoce da doença, as três moléculas identificaram o Mal de Alzheimer com 90 por cento de precisão.

"Os resultados deste estudo, embora preliminares, mostram um grande potencial para se tornarem um marco no tratamento da doença," disse German.

Scientists Crack Molecular Code Regulating Neuronal Excitability

ScienceDaily (Mar. 21, 2011) — A key question in protein biochemistry is how proteins recognize "correct" interaction partners in a sea of cellular factors. Nowhere is that more critical to know than in the brain, where interactions governing channel protein activity can alter an organism's behavior. A team of biologists at the Salk Institute for Biological Studies has recently deciphered a molecular code that regulates availability of a brain channel that modulates neuronal excitability, a discovery that might aid efforts to treat drug addiction and mental disorders.

Left images show localization of SNX27 (shown in green) and NeuN (shown in red) in the CA1 region of the hippocampus, the brain's learning and memory center. Right image shows superimposition of magnified region.

In the Proceedings of the National Academy of Sciences, Paul Slesinger, Ph.D., Associate Professor in the Clayton Foundation Laboratories for Peptide Biology, and colleagues detail how a regulatory factor called SNX27 distinguishes a brain channel protein called GIRK (short for G-protein-coupled inwardly rectifying potassium channels) from structurally similar proteins and then targets it for destruction.

That work extends the group's 2007 study showing that when SNX27 proteins capture GIRK channels, reducing the number of channels at their rightful destination, the cell membrane. "We were curious about what determined the selectivity of this interaction," says Slesinger. "We knew that SNX27 interacted with a structural motif found on GIRK channels but many channel proteins display a similar motif. We wanted to know what allowed SNX27 to specifically choose GIRK channels."

Knowing this is critical because of the connection of GIRK channels to substance abuse. Slesinger and others have shown that alcohol or club drugs linked to sexual assault (GHB) affects GIRK channel function in the brain. Loss-of-inhibition behaviors associated with abuse of these substances result from the fact that GIRK channels allow potassium ions to leak out of a stimulated neuron, thereby dampening a cell's excitability.

In the new study Slesinger's team confirmed that SNX27 resides in neurons, just below the membrane where active GIRK channels sit. Additional experiments using brain cells manipulated to express abnormally high SNX27 levels showed that cells were less responsive to drugs that activate channels, suggesting that SNX27 waylays membrane-bound GIRKs and blocks their function.

The fact that SNX27 displays a common protein-interaction signature called PDZ domain suggested how SNX27 grabs its partner: GIRKs contain a short, 4-residue sequence that binds to PDZ domains, a recognition motif Slesinger likens to a zip code. But channels similar to GIRKs, called IRKs, displayed an almost identical sequence but were impervious to destruction by SNX27. "We were puzzled by this similarity and swapped the 4-residue code in IRK with the corresponding sequence from GIRK," says Slesinger. Surprisingly, this IRK/GIRK hybrid did not bind SNX27, indicating that the IRK lacked other elements necessary for SNX27 recognition.

To define these new elements, Slesinger consulted with a long-standing collaborator, Senyon Choe, Ph.D., professor in Salk's Structural Biology Laboratory. Choe is an expert on a technique known as X-ray crystallography, used to determine the three-dimensional structure of proteins. The team scrutinized crystallized forms of SNX27 wrapped around the GIRK binding motif to try to visualize where the proteins made contact.

"We observed a binding cleft in the SNX27 PDZ domain and a region that formed another pocket with a lot of positive charges," says Slesinger. "The GIRK fragment lying there had a negative charge upstream of the 4-residue "zip code." That suggested that this second site allowed a previously unknown electrostatic interaction between these two proteins." Therefore, SNX27 may recognize a 6-residue motif, like the "zip plus 4" code.

More swap experiments targeting the GIRK negatively charged region confirmed the hypothesis. Synthetic forms of GIRK lacking the region no longer bound to SNX27. By contrast, an artificial version of IRK engineered to contain the GIRK negative charges homed to SNX27.

Most significant were experiments conducted by Bartosz Balana, Ph.D., a postdoctoral fellow in the Slesinger lab and the study's first author. Balana measured currents from cells engineered to carry GIRK channels lacking the charged region and found that GIRK currents were no longer dampened by SNX27, while cells expressing IRK channels displaying the false GIRK "address" now responded to SNX27. "This functional assay pin-pointed residues that dictate SNX27 binding beyond the normal PDZ recognition sequence," says Bartosz. "This supports a two-site binding model and emphasizes that second site can overrule binding at the classical site."

An interesting corollary to GIRKs' involvement in drug-related behavior is that SNX27 levels reportedly increase in rodent models of addiction to stimulants like cocaine and methamphetamine. Selectively blocking this newly identified interaction between GIRK and SNX27 might thwart addiction. "Now we are able to better understand the role of these channels in responses to drugs of abuse. It is our hope that that this work will lead to new strategies to treat diseases such as alcoholism or even, diseases of excitability, such as epilepsy." says Slesinger.

Also contributing to the study were Kalyn Stern and Laia Bahima of the Slesinger Lab and Innokentiy Maslennikov, and Witek Kwiatkowski of Choe's Structural Biology Laboratory.

The study was funded by grants from the NIH and the National Alliance for Research on Schizophrenia and Depression.

Mutant Prions Help Cells Foil Harmful Protein Misfolding

ScienceDaily (Mar. 21, 2011) — Romping clumps of misfolded proteins are prime suspects in many neurological disorders including Alzheimer's, Parkinson's, and Creutzfeld-Jakob Disease. Those diseases are devastating and incurable, but a team of biologists at Brown University reports that cells can fix the problems themselves with only a little bit of help. The insight suggests that there are more opportunities to develop a therapy for protein misfolding than scientists had thought.

Mutant prions help cells The red color of the the yeast cell colony, upper right, indicates that it has been cured of a prion infection with the help of a beneficial mutant prion. The colony to its left did not receive a dose of mutants. The unhealthy colonies on the bottom row remained infected because researchers hindered the cells' own quality assurance mechanism. 

"There are multiple steps that you could target," said Susanne DiSalvo, a Brown biology graduate student and lead author of a paper published in advance online March 20 in Nature Structural and Molecular Biology.

In the study, the research team, led by Tricia Serio, associate professor of medical science, explains how two different beneficial mutant prions managed to foil the amplification of harmful clumps of misfolded proteins in yeast. Cells have an internal quality assurance system to break up and refold misfolded proteins, but that system can be overwhelmed by diseases. DiSalvo was the first to observe that the mutants act at distinct stages to tip the balance back in favor of the cells, allowing them to overcome the problem.

Serio says the molecular mechanisms appear to explain how similar mutants solve protein misfolding in mammals, including people. The phenomenon had been poorly understood and has never been exploited to develop a successful therapy.

Misfolding is a vulnerable process

Until now most scientists guessed that the only way to stop the runaway misfolding was right at the beginning and assumed the mutants must be blocking that first step to keep the protein in a harmless form. DiSalvo's work instead suggests that there are many opportunities throughout the process where even a mild intervention could give cells what they need to gain the upper hand, Serio said.

"That's one of the biggest outcomes of Susanne's work: that if you just even slightly interfere with this process, the cell can deal with it and get rid of it," Serio said. "The dogma in the field is that these conformations were so abnormal the cell couldn't resolve them. But what we've found is that this process of misfolding is so efficient the cells can't keep up with it. If you make it even just a little bit less efficient the cell can get rid of the pathological state."

One mutant prion, Q24R, hinders the ability of misfolded proteins to aggregate into harmful clumps. It's like a dryer sheet that cuts down on static cling and makes it easier to fold laundry. Another helpful mutant prion known as G58D, assists the cell by speeding up its ability to unfold and refold misfolded proteins. That's more like a friend who helps untangle strings of holiday lights when they come out of storage.

DiSalvo's experiments showed how the mutants and cells work together. Cells would only be cured when she both added a mutant and allowed the cells' own quality assurance system to work. Adding the mutant G58D, for example, could cure a cell of infection by the Sup35 prion, but if she perturbed the cell's quality assurance system then G58D would not work.

The results show the importance of delving deeply into molecular networks, said Stefan Maas, who oversees Serio's and other cellular signaling grants at the National Institutes of Health.

"These results are a great example of the power of system-level studies," Maas said. "By showing how two beneficial mutants cure the cell of prions, this study has revealed that small changes applied to distinct components of a molecular network can dramatically alter the outcome for the cell. These new insights may lead to new strategies for preventing or treating disorders that involve protein deposits."

But those strategies may require turning proteins into pills. Serio noted that while beneficial mutant prions confer resistance to prion infection in nature, they haven't been successful in reversing an established infection because sustained delivery into the body is too challenging. However, a small molecule drug mimic, if developed, could target infected tissues more effectively over a longer period to slow or perhaps even reverse disease progression.

In the paper the researchers conclude, "A system-based approach to prion intervention represents a potentially promising direction in which to explore future therapies."

Other authors on the paper include Brown researchers Aaron Derdowski and John Pezza.

Spacebound Bacteria Inspire Earthbound Remedies

ScienceDaily (Mar. 21, 2011) — Recent research aboard the Space Shuttle is giving scientists a better understanding of how infectious disease occurs in space and could someday improve astronaut health and provide novel treatments for people on Earth.The research involves an opportunistic pathogen known asPseudomonas aeruginosa, the same bacterium that caused astronaut Fred Haise to become sick during the Apollo 13 mission to the moon in 1970.

Scanning electron micrograph of Pseudomonas aeruginosa cultured on board Shuttle mission STS-115, as part of the MICROBE experiment (magnification 12,000X). 

Scientists studying the bacterium aboard the Shuttle hope to unlock the mysteries of how disease-causing agents work. They believe the research can lead to advanced vaccines and therapies to better fight infections. The findings are based on flight experiments with microbial pathogens on NASA space shuttle missions to the station and appear in a recent edition of the journal Applied and Environmental Microbiology.

"For the first time, we're able to see that two very different species of bacteria -- Salmonella and Pseudomonas -- share the same basic regulating mechanism, or master control switch, that micro-manages many of the microbes' responses to the spaceflight environment," said Cheryl Nickerson, associate professor at the Center for Infectious Diseases and Vaccinology, the Biodesign Institute at Arizona State University (ASU) in Tempe. "We have shown that spaceflight affects common regulators in both bacteria that invariably cause disease in healthy individuals [Salmonella] and those that cause disease only in people with compromised immune systems [Pseudomonas]."

By studying the global gene expression patterns in bacterial pathogens like Pseudomonas and Salmonella, Nickerson's team learned more about how they react to reduced gravity.

Pseudomonas aeruginosa can coexist as a benign microbe in healthy individuals, but poses a serious threat to people with compromised immune systems. It is the leading cause of death for those suffering from cystic fibrosis and is a serious risk to burn victims. However, a high enough dosage ofSalmonella typhimurium always will cause disease, even in healthy individuals.

During the initial study in 2006, two bacterial pathogens,Salmonella typhimurium and Pseudomonas aeruginosa, and one fungal pathogen, Candida albicans, were launched to the station aboard space shuttles. They were allowed to grow in appropriately contained vessels for several days. Nickerson's team was the first to evaluate global gene and protein expression (how the bacteria react at the molecular level) and virulence changes in microbes in response to reduced gravity.

"We discovered that aspects of the environment that microbes encountered during spaceflight appeared to mimic key conditions that pathogens normally encounter in our bodies during the natural course of infection, particularly in the respiratory system, gastrointestinal system and urogenital tract," Nickerson said. NASA's Advanced Capabilities Division Director, Benjamin Neumann added that, "This means that in addition to safeguarding future space travelers, such research may aid the quest for better therapeutics against pathogens here on Earth."

The initial study and follow-on space experiments show that spaceflight creates a low fluid shear environment, where liquids exert little force as they flow over the surface of cells. The low fluid shear environment of spaceflight affects the molecular genetic regulators that can make microbes more infectious. These same regulators might function in a similar way to regulate microbial virulence during the course of infection in the human body.

"We have now shown that spaceflight conditions modified molecular pathways that are known to be involved in the virulence of Pseudomonas aeruginosa," said Aurélie Crabbé, a researcher in Dr. Nickerson's lab at ASU and the lead author of the paper. "Future work will establish whether Pseudomonasalso exhibits increased virulence following spaceflight as didSalmonella."