Biblioteca oferece treinamento em bases de dados 'Dynamed', 'Gideon' e 'Medline with full text' na Ensp, dia 19/11

A Biblioteca de Saúde Pública, do Instituto de Comunicação e Informação Científica e Tecnológica em Saúde (Icict/Fiocruz), convida docentes, pesquisadores, bolsistas, estagiários, bibliotecários, profissionais de informação e alunos de pós-graduação da Fiocruz para o treinamento em três importantes bases de dados da empresa EBSCO. São elas: Dynamed, Gideon e Medline with full text. O treinamento tem como objetivo fornecer uma visão sistemática das bases de dados bibliográficas e respectivos mecanismos de busca. O treinamento ocorre no dia 19/11, no Salão Internacional da Ensp, e será ministrado pelos representantes da EBSCO.

 

Informações básicas sobre as bases de dados:

 

 • DynaMed - plataforma de atualização profissional que responde a praticamente as questões clínicas durante a prática médica totalmente baseadas em evidências.

 

• GIDEON (Global Infectious Disease and Epidemiology Network) - é a base de dados sobre que oferece informação atualizada baseada em evidência médica a respeito do diagnóstico, tratamento e aprendizado nas áreas de doenças tropicais e infecciosas, epidemiologia e microbiologia de todos os países.

 

• Medline with full text - é a mais abrangente fonte de periódicos de medicina em texto completo do mundo, provendo artigos na íntegra de aproximadamente 4.800 periódicos indexados na MEDLINE. Destes, mais 1.450 possuem também texto completo para muitos dos periódicos mais utilizados na MEDLINE, inclusive o The New England Journal of Medicine. Possui ainda mais de 1.400.000 artigos em texto completo retroativos a 1965.

 

Serviço:

Data: 19/11/2010 das 9h às 13h

Local: Salão Internacional da Ensp

Rua Leopoldo Bulhões, 1480 - Prédio da Ensp – 4º andar

Good news for 'good' cholesterol

Positive results inject life into strategy to treat heart disease.

A strategy for lowering heart-disease risk that once seemed to be a dead end is showing fresh promise. Decades of animal studies and epidemiological data had suggested that raising blood levels of high-density lipoprotein — HDL, or 'good' cholesterol — might have a stronger protective effect against heart disease than statins, drugs that lower levels of low-density lipoprotein ('bad' cholesterol or LDL). But in 2006, a US$1-billion trial of torcetrapib, an HDL-raising drug, found it seemed to increase patients' risk of death, casting a pall of doubt over the entire field. This week, the first study since to focus on the class of drugs that boosts HDL levels may offer good news for the approach.

The study, published in The New England Journal of Medicine¹, was a 1,623-patient trial investigating the safety of anacetrapib, a drug functionally similar to torcetrapib, developed by pharmaceutials giant Merck, based in Whitehouse Station, New Jersey. The drug inhibits a protein called CETP, which raises HDL. The trial found with 94% confidence that anacetrapib does not harm patients — in contrast to the 15,000-patient trial of torcetrapib, also a CETP inhibitor. When Pfizer halted that trial early², many companies stopped working on CETP blockers. Researchers were left wondering whether torcetrapib's failure was down to unexpectedly high toxicity in that compound, whether the inhibition of CETP itself is harmful, or whether the idea that raising HDL levels lowers risk is flawed.

The anacetrapib trial also tracked the drug's effects on LDL and HDL levels, which, according to Christopher Cannon, a cardiovascular researcher at Brigham and Women's Hospital in Boston, Massachusetts, and the study's principal investigator, are "jawdropping". After 24 weeks on the drug, patients experienced a 138% increase in HDL levels. In contrast, exercising and changing diet might only raise HDL by 10%, says Cannon. The participants, all of whom were also on statins, experienced a further 40% reduction in LDL levels.

Although the study wasn't large enough to look at the effect of anacetrapib on heart disease, the researchers noted some positive trends: 3.3% of patients taking the drug experienced heart attacks, stroke or other kinds of cardiovascular events, compared with 5.3% of patients in the placebo group.

The drug's apparent safety is encouraging, says Prediman Shah, director of cardiology and atherosclerosis research at Cedars-Sinai Medical Center in Los Angeles, California, "but there are some interesting red flags". One, he says, has to do with c-reactive protein (CRP), a marker of inflammation in blood that tends to drop as patients regulate their cholesterol with statins or lifestyle changes. Despite the huge changes in LDL and HDL levels, CRP levels actually increased slightly.

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Shah also says he is surprised that such enormous shifts in HDL levels yielded such small clinical benefits. "In all fairness, the study wasn't powered to test that," says Shah, but if epidemiological predictions on HDL's benefits are correct, the drug should virtually "confer immortality".

Whether raising HDL really works won't become clear until data from larger studies begin to emerge, Shah says. An international, 30,000-patient trial testing anacetrapib's efficacy will begin next year, but results won't come in until at least 2014 (see Table 1). Meanwhile, results on another CETP inhibitor called dalcetrapib, developed by Roche, are expected in 2013. 

• References

  1. Cannon, C. P. et al. N. Engl. J. Med. doi:10.1056/NEJMoa1009744(2010).
  2. Pearson, H. Nature 444, 794-795 (2006).

Disease-in-a-dish approach gives clues to Rett syndrome

Unregulated jumping genes are a possible culprit for the debilitating disease.

An L1 'jumping gene' was more active in brain tissue lacking a key protein (below) then in a healthy control (above).

A 'disease in a dish' experiment, in which skin cells from sufferers of the neurodevelopmental disorder Rett syndrome were made to develop into neurons, has provided insight into what goes wrong in the brains of people with the condition. The result marks a crucial step towards clinical applications for a technique that is seen as a smoking hot field.

The approach involves reprogramming cells from people with a particular disorder into an embryonic state known as induced pluripotent stem cells (iPS cells). The cells are then differentiated into types of tissue that are affected by the condition. iPS cells were first created from human tissue in 2007, and since then scientists have been racing to build libraries of patient cell lines in the hope that the disease-in-a-dish technique will allow them to study the mechanisms of different conditions.

"You can't just take blood or skin. You need to look at the tissue where [the disease mechanism] is happening," says Fred Gage, a geneticist at the Salk Institute for Biological Studies in La Jolla, California.

Gage and his colleagues applied the approach to Rett syndrome, a rare disorder that causes children to develop increasing problems with movement, coordination and communication. Researchers have known for more than a decade¹ that the syndrome can be caused by a mutation in a gene called MECP2, which encodes the protein MeCP2. Their latest study, published today in Nature², finally offers clues as to how such mutations lead to disease.

Beyond mouse models

The team examined the role of MeCP2 in mice, and found that knocking out the gene in neurons leads to increased activity of a type of 'jumping gene' called an L1 retrotransposon. These sequences of DNA can detach themselves from the genome, replicate, and reinsert themselves elsewhere. In their latest study, Gage and his colleagues showed that neurons derived from iPs cells from people with Rett syndrome showed more L1 activity than did healthy controls, just as in the MeCP2-deficient mouse models. The researchers checked their results in brain tissues taken from patients after they died.

“You can't just take blood or skin. You need to look at the tissue where the disease mechanism is happening.”

Gage's past experiments have shown that such jumping genes are naturally active in the brain, leading to speculation that they may play a role in generating diversity among neurons³, however, this activity is tightly controlled. The altered L1 activity in Rett neurons suggests a possible role in the disease, perhaps in creating too little or too much diversity, say the researchers.

The same team provided further evidence of differences between Rett and healthy neurons in a paper published last week in Cell⁴. That study, also based on the disease-in-a-dish approach, showed that neurons derived from people with Rett syndrome had, among other differences, considerably fewer synapses than did healthy controls.

The two threads of evidence "provide one of those 'mmmm' experiences, and make you start to really think about what goes wrong in kids with Rett syndrome," says Evan Snyder, a stem-cell biologist at the Burnham Institute for Medical Research in La Jolla.

However, he points out that the connections between L1 activity, MeCP2 and the disease, although impressive, are still just associations. Demonstrating just where cells go awry during development is not simple. "We are still at the validation stage," says Snyder.

A jump forwards

Gage admits that his experiments raise more questions than they answer. Are elevated L1-activity levels and reduced numbers of synapses causally related? Can either be said to cause the symptoms of Rett syndrome? "There is no direct evidence on either yet," says Gage.

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But Gage's colleague Alysson Muotri, a neuroscientist at the University of California, San Diego, is a little bolder, citing a 2005 study by the team that showed that some neuronal genes are targeted by L1 insertions³. "To me, this is clear evidence that L1s can impact the genome of neuronal cells," he says. The team will now take a closer look at the effect of manipulating L1 levels in mouse models and in human neurons.

Despite lingering questions, Gage and his team's successful study is likely to accelerate competition among researchers working with the disease-in-a-dish approach. Snyder, for example, has a library of some 50 lines of iPS cells, covering Alzheimer's disease, spinal muscular atrophy, bipolar disorder and other conditions, which he is also probing for causal mechanisms of disease.

But challenges remain. The current technology is so labour intensive that a key goal of the approach, using the cells to test drug candidates, is impossible for now. "It is not viable to take this to a drug company," says Gage. Conditions such as schizophrenia or autism, for which there is no clearly related gene, will also be difficult to study using the technique. 

References

1. Amir, R. E. et al. Nature Genetics 23, 185-188 (1999).
2. Muotri, A. R. et al. Nature 468, 443-446 (2010).
3. Muotri, A. R. et al. Nature 435, 903-910 (2005).
4. Marchetto, M. C. N. et al. Cell 143, 527-539 (2010).

Evolutionary Relationships Hold, Even in Our Guts

It's all relative. The bacteria in this gorilla's gut
are similar to those of another gorilla species.

The human body is coated with bacterial cells. They live on our skin and between our teeth. They particularly like our warm, nutrient-filled gut, where they help digest food, make vitamins, and produce some seriously smelly gas. But when it comes to these gut bacteria, we are not what we eat. A new analysis of feces from humans and several other primates finds that evolutionary history, not diet, determines the makeup of our intestinal bugs.

Babies are born sterile, then they start picking up bacteria from their mothers. These microbes multiply and fill the intestines; one adult's gut can hold a thousand species. But it's not clear what exactly influences the makeup of that community—that is, what particular species of bacteria, in what quantities, hang out in our guts. It could depend mainly on what we get from our mothers, on what we eat, or on some other factor. Scientists have started using new genetic techniques to work out whether different species of animals have different communities; some studies in recent years have concluded that animals with similar diets have similar microbial communities.

To find out if diet was really key, Yale University evolutionary biologist Howard Ochman gathered samples of feces from 26 animals in the wild, representing three subspecies of chimpanzees, two species of gorillas, and two humans—one from Arizona and one from the Central African Republic, whose poop had originally been misidentified as belonging to an ape. Ochman didn't go out in the field for these samples; most were in freezers of colleagues who had collected them for other studies. "Basically, you get them by telephone," he says.

Ochman and colleagues sequenced the bacterial DNA in each sample and focused on a particular gene whose sequence varies from species to species. The primates varied in both the types of bacteria their guts contained and the number of bacteria of each type. The team used this data to construct a tree of the bacterial relationships among the primates. Primates with many of the same number and kind of gut bacteria were placed close together on the tree, and vice versa.

To Ochman's surprise, the tree matched the evolutionary relationship of the primates. The gut bacteria of the humans more closely resembled those of the two chimp subspecies, for example, than they did those of the gorilla species. "We were just amazed," Ochman says. Diet probably isn't a factor, because the two humans shared the same gut bacteria even though they lived in vastly different parts of the world.

Ochman doesn't know why our microbial communities are so similar to our evolutionary relationships, but he suspects there may something about a species' gut physiology that makes it welcoming to a particular community of microorganisms. His team reports its findings online today in PLoS Biology.

"I like their approach" of building a tree based on comparing the makeup of microbial communities in different animals' guts, says microbiologist and infectious disease specialist David Relman of Stanford University in Palo Alto, California. He agrees that these data suggest that evolutionary relationships are more important than diet, but without knowing the animals' diet, he says, "it's hard to know how strong a statement one can make about the role of diet."

Ganhador do Nobel de Medicina faz conferência na Fiocruz nesta quinta-feira (18/11)

O pesquisador Eric Kandel, prêmio Nobel de Medicina, fará uma conferência na Fiocruz nesta quinta-feira (18/11), às 11h, na Residência Oficial. O título da palestra será There is life after the Nobel Price: A molecular approach to the epidemiological gateway hypothesis of drug abuse. Laureado em 2000, Kandel dividiu o prêmio com Arvid Carlsson ePaul Greengard. Eles foram agraciados por suas descobertas relativas à transdução de sinal no sistema nervoso.

Kandel, que foi diretor do Center for Neurobiology and Behavior da Columbia University, em Nova York, foi premiado por suas descobertas de como a eficiência das sinapses pode ser modificada, e quais mecanismos moleculares participam desse processo. Ele demonstrou como as mudanças da função sináptica são centrais para o aprendizado e a memória. Pesquisador do Howard Hughes Medical Institute da Columbia University, Kandel nasceu na Áustria, em 1929, e é cidadão americano.

Mais informações:

http://www.hhmi.org/research/nobel/kandel.html e

http://nobelprize.org/nobel_prizes/medicine/laureates/2000/