Aparelho desenvolvido nos EUA identifica causa da pneumonia

Um novo aparelho desenvolvido nos EUA promete identificar o agente causador da pneumonia.

A doença pode ser causada por bactérias, vírus, fungos e protozoários, mas o microrganismo responsável só é identificado em até 40% dos casos da infecção.

A invenção funciona de forma simples: o paciente tosse no bocal do aparelho, que, segundo os fabricantes, é capaz de separar as partículas do pulmão das da boca.

Depois, o filtro é levado para análise clínica, que identifica o agente causador da pneumonia.

O aparelho, que se chama PneumoniaCheck, foi desenvolvido no Georgia Institute of Technology, em Atlanta (EUA) e teve a sua comercialização aprovada pelo FDA (agência que regulamenta remédios nos EUA).

No mês passado, ele foi lançado comercialmente naquele país e poderá ser vendido em outros locais nos próximos dois anos, segundo o fabricante.

Em geral, o diagnóstico da pneumonia é feito por exame clínico e físico, radiografia dos pulmões e exame de sangue, que pode mostrar sinais que indicam uma infecção.

Mas o exame é baseado em presunções e não é definitivo, segundo Elie Fiss, professor de pneumologia da Faculdade de Medicina do ABC e pneumologista do hospital Oswaldo Cruz.

"Para ter um exame com 100% de precisão, é preciso descobrir o agente responsável. Como esse diagnóstico é difícil e pode levar semanas, tratamos o quadro clínico baseado nos sintomas e exames com rapidez para que o quadro não se agrave."

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MENOS ANTIBIÓTICOS

Um estudo que mostra a eficácia do novo aparelho foi publicado em dezembro no "Journal of Medical Devices", por técnicos do mesmo instituto que desenvolveu o PneumoniaCheck.

A pesquisa aponta que os filtros do aparelho são capazes de coletar 99,9% das partículas com vírus e bactérias da amostra das vias superiores do pulmão.

Segundo Sarah Ku, coordenadora de produtos da MD Innovate, empresa fabricante do aparelho, a identificação do agente leva a um tratamento mais personalizado, com menos antibióticos, que, se usados amplamente, podem aumentar a resistência das bactérias.

Hoje, os antibióticos são as drogas mais usadas contra pneumonia, mesmo sem a identificação do agente causador da doença.

Segundo Fiss, as diretrizes das sociedades médicas apontam que as bactérias são as maiores responsáveis pela pneumonia. Para eliminar a doença, são usados antibióticos de maior espectro.

Segundo Mauro Zamboni, da Sociedade Latino-Americana do Tórax, o aparelho é interessante, e algo similar já vem sendo testado para doenças como a tuberculose.

Já para Fiss, aparelho não deve ser eficaz, devido à dificuldade em separar as partículas das vias aéreas inferiores e superiores. "Faltam estudos maiores com grupo-controle e placebo."

Pesquisa da USP mostra como cigarro causa artrite

Um mecanismo que desencadeia a artrite reumatoide em fumantes foi identificado por pesquisa da FMRP (Faculdade de Medicina de Ribeirão Preto), da USP.

Já se sabia que quem tem predisposição genética e fuma pode sofrer dessa doença inflamatória crônica, que causa dores e rigidez matinal nas mãos e nos pés.

Agora, o estudo do biomédico Jhimmy Talbolt, defendido como dissertação de mestrado na última semana, revela como isso acontece.

Quando a pessoa fuma, uma das células do sistema de defesa -a TH17- é sensibilizada e fica doente.

Ao ser estimulada pelos hidrocarbonetos aromáticos da fumaça do cigarro, a TH17 passa a orientar o sistema de defesa a destruir articulações das mãos, pés, joelhos, punhos, cotovelos e tornozelo.

O professor de reumatologia da FMRP e orientador de Talbot, Paulo Louzada Junior, disse que o resultado pode ser o ponto de partida para o desenvolvimento de uma droga que reduza os sintomas da doença com mais eficiência ou até interrompa o processo de deterioração das articulações periféricas.

Segundo Louzada Junior, a artrite reumatoide atinge 1% da população adulta brasileira e a descoberta é inédita na literatura científica.

A pesquisa, com financiamento do CNPq e da Fapesp, acompanhou durante dois anos 138 pacientes com artrite reumatoide (metade fumante) e um grupo-controle com 129 pessoas sadias.

Foram comparadas as mutações genéticas do sangue de pacientes fumantes e não fumantes com o sangue do grupo-controle.

Essas informações foram relacionadas aos dados clínicos de cada um, constatando que a fumaça do cigarro e a célula TH17 estavam ligadas à artrite reumatoide.

"Em modelos experimentais em camundongos, constatamos que os receptores de hidrocarboneto arila [da fumaça do cigarro] provocavam o aumento do número das células TH17 e a piora da doença", diz Talbot.

Louzada Junior explica que o receptor da célula TH17 se danifica com a fumaça porque é sensível ao hidrocarboneto arila.

"Esse receptor elimina poluentes dentro do corpo. Só que, se tiver essa alteração genética, o sistema pode estimular a célula do sistema de defesa a causar a doença."

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FATOR AGRAVANTE

Para o reumatologista José Goldemberg, da Unifesp, conhecer esse mecanismo possibilita tratar o problema com conhecimento científico. "Sem a "achometria", que é a medida do achismo."

Segundo Ari Halpern, reumatologista do hospital Albert Einstein, muitos estudos têm demonstrado relação entre o cigarro e a artrite e, entre os fatores que alteram o prognóstico da doença, o fumo é um dos mais importantes.

Nível elevado de triglicérides aumenta risco de derrame, revela pesquisa

Estudo dinamarquês apontou que aumento do nível no sangue em jejum é tão perigoso quanto possuir colesterol alto

Muitas vezes deixado de lado por médicos e pacientes, o triglicérides pode se tornar mais um marcador de risco de doenças cardiovasculares e ter um peso tão importante quanto o colesterol na prevenção de um acidente vascular cerebral (AVC), popularmente chamado de derrame.

É o que aponta um estudo dinamarquês que concluiu que ter no sangue altos níveis de triglicérides em jejum é tão perigoso quanto possuir colesterol elevado. A descoberta indica que o triglicérides aumentado eleva os riscos de um AVC isquêmico - aquele em que há o entupimento do vaso por causa do depósito de placas de gordura, que bloqueiam o fluxo sanguíneo.

Os triglicérides são partículas presentes em alimentos calóricos, como bolachas, bolos, massas, enlatados e frutos do mar. Cerca de 80% dos triglicérides são resultado da alimentação e, por isso, podem ser tratados apenas com dieta balanceada. O colesterol, ao contrário, é produzido em boa parte pelo organismo e, para baixá-lo, é necessário fazer uso de medicação.

Os pesquisadores acompanharam 7.579 mulheres e 6.372 homens - todos mediram os níveis de triglicérides em jejum e de colesterol logo no início do estudo (1976-1978). Eles foram acompanhados por até 33 anos.

Nesse período, 837 mulheres e 837 homens tiveram AVC isquêmico. Segundo os pesquisadores, os resultados demonstram que o gradual aumento dos níveis de triglicérides foi associado ao maior risco de sofrer um AVC. As conclusões foram publicadas na Annals of Neurology.

Nas mulheres, níveis acima de 442 mg/dl indicaram um risco 3,9 vezes maior de ter o problema em comparação com mulheres com níveis normais. Em níveis semelhantes em homens, o risco variou de 1,2 a 2,3, respectivamente. "As diretrizes atuais de prevenção de AVC trazem recomendações sobre os níveis de colesterol desejáveis, mas não citam os níveis desejáveis de triglicérides", afirma Marianne Benn, autora do estudo.

Ação. O estudo dinamarquês constatou que os níveis elevados de triglicérides em jejum indicam que há altos níveis de resíduos de lipoproteínas no sangue - partículas semelhantes ao LDL (chamado de mau colesterol).

Essas partículas são minúsculas e densas, o que facilita que sejam incorporadas para dentro da parede interna dos vasos, provocando um quadro crônico de inflamação e, consequentemente, estimulando o crescimento de placas de gordura.

"Quando essas partículas estão em excesso, elas favorecem a infiltração para dentro do vaso sanguíneo. Até então, essa era uma prerrogativa bem estabelecida para o colesterol e agora passa a ser também para os triglicérides", diz o cardiologista Marcelo Ferraz Sampaio, coordenador do Laboratório de Biologia Molecular do Instituto Dante Pazzanese.

"Existe uma tendência de preocupação apenas com o colesterol. Mas esse estudo demonstra que os triglicérides são tão importantes quanto os níveis de LDL. Antes, havia uma suspeita de que só as partículas de LDL aderiam à parede da artéria e o estudo demonstrou o oposto", diz a neurocirurgiã Julieta Gonçalves Silva, da Unifesp.

Segundo Julieta, a suspeita de que níveis altos de triglicérides também eram prejudiciais sempre existiu, mas apenas agora, com esse estudo, é que as suspeitas foram confirmadas. "Cabe aos neurologistas e cardiologistas ficarem atentos para tratar os pacientes preventivamente."

Para o neurologista Rubens Gagliardi, vice-presidente da Academia Brasileira de Neurologia, apesar de o estudo demonstrar os malefícios do triglicérides, a hipertensão arterial ainda apresenta mais riscos para AVC. "O triglicérides isolado é, sim, um fator de risco, mas menos importante que o colesterol. Seus níveis altos podem ser resolvidos com controle dietético, ao contrário do colesterol", diz.

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ENTENDA A DOENÇA

O AVC:

É o entupimento ou rompimento de vasos sanguíneos cerebrais, caracterizados pela perda rápida de função neurológica.

As causas:

Malformação arterial cerebral (aneurisma), cardiopatia, tabagismo, colesterol e hipertensão arterial - a pressão alta é um dos principais fatores de risco. O diagnóstico pode ser obtido por meio de exames de imagem, tomografia computadorizada e ressonância magnética.

Sintomas:

Variam de acordo com a área do cérebro afetada pela interrupção da irrigação, mas, em geral, são formigamento das mãos, perda de força no braço e perna (do mesmo lado), dificuldades de fala e, em casos mais graves, desmaio.

Sequelas: 

Em geral, pacientes que sofrem AVC ficam com sequelas físicas e motoras. As mais comuns são perda do movimento de um lado do corpo, formigamento e alterações da fala. 



Missing DNA Helps Make Us Human

ScienceDaily (Mar. 9, 2011) — A new study demonstrates that specific traits that distinguish humans from their closest living relatives -- chimpanzees, with whom we share 96 percent of our DNA -- can be attributed to the loss of chunks of DNA that control when and where certain genes are turned on. The finding mirrors accumulating evidence from other species that changes to regulatory regions of DNA -- rather than to the genes themselves -- underlie many of the new features that organisms acquire through evolution.

Chimpanzees and humans are minimally different genetically, but the small differences are what make us human, according to a team of researchers who identified segments of non-coding DNA missing in humans that exist in chimpanzees and other animals.

Seeking specific genetic changes that might be responsible for the evolution of uniquely human traits, Howard Hughes Medical Institute investigator David Kingsley and colleagues at Stanford University scanned the human genome for features that set us apart from other mammals. The team found 510 segments that are present in chimps and other animals but missing from the human genome. Only one of the missing segments would actually disrupt a gene; the remaining 509 affect the DNA that surrounds genes, where regulatory sequences lie.

Careful analysis of a handful of these segments demonstrated that loss of regulatory DNA could explain how humans developed some features not found in other animals -- such as big brains -- as well as how they lost features common in other species, such as sensory whiskers and spiny penises. Their findings are published in the March 10, 2011, issue of the journal Nature.

Genes -- segments of DNA that carry the blueprints for proteins -- make up less than two percent of the human genome. Hidden within the remainder of our more than three billion base pairs of DNA are regulatory sequences that control when and where genes are expressed. Direct alterations to a gene can have dramatic effects, sometimes killing an organism or rendering it sterile. "In contrast, if you alter the way [a gene] turns on or off at a particular place in development, that can have a very large effect on a particular structure, but still preserve the other functions of the gene," Kingsley says. "That tends to be the sort of alternation that's favored when a new trait is evolving."

Kingsley's previous work with stickleback fish, a small spiny fish whose recent and rapid adaptation to a wide range of aquatic environments has made it ideal for evolutionary studies, have shown time and again that changes in regulatory DNA can have profound effects on an organism's traits. So when Kingsley and his colleagues searched for regions of the genome common to chimps, macaques, and mice but missing in the human genome, they weren't surprised that the sequence differences they found were almost exclusively outside of genes.

Collaborating with computational biologist Gill Bejerano's lab at Stanford, the team pinpointed 510 genetic sequences that appear in the genomes of chimps and other animals, but are "surprisingly missing" from the human genome, Kingsley says. To narrow the list so that they could focus on the changes most likely to have altered when and where particular genes were expressed, the researchers conducted a computer analysis to identify deletions that were clustered around particular genes. "We saw more changes than you would expect near genes involved in steroid hormone signaling," Kingsley says. A number of deletions also appeared near genes involved in neural development, their analysis revealed.

But technology could only take the team so far. To zero in on specific deletions that might control human traits, the team relied on manpower: neuroscientists, physical anthropologists, developmental geneticists, and more. "We had a team of interested graduate students, postdocs, and developmental biologists poring through this list," Kingsley says. The team searched for sequences near genes known to play key roles in development, especially those known to control traits that differ between humans and other animals. "It was a fun detective hunt that led to lots of interesting discussions," he says.

The team came up with a couple dozen deletions near genes they suspected might be involved in the evolution of particular human traits. But the researchers still didn't know the normal functional roles of the missing sequences. So Kingsley and his colleagues isolated those genetic sequences from organisms that still had them (chimps or mice), attached the sequences to a reporter gene that produces a simple blue color reaction in living cells, and injected the resulting sequences into fertilized mouse eggs. By monitoring the blue color reaction in developing mice, they could see exactly where and when the sequence was turning on gene expression during embryonic or postnatal development. This gave them a way to link "the biology of the gene, the molecular change that had happened in humans, and the specific anatomical place where it really was expressed during normal development," Kingsley explains.

These experiments highlighted two segments of DNA that humans lack, but that appear to play a particularly important role in development of mice and other non-human mammals. The first is a segment of DNA that, in most animals, occurs near the gene that codes for the androgen receptor, which is associated with a variety of male-specific traits. "Males have beards, females don't," Kingsley says. "That's an example of an androgen receptor-dependent process." When the researchers inserted this sequence into mouse eggs, "what we got were blue sensory whiskers and blue genitalia," Kingsley says, indicating that when present, the sequence causes the androgen receptor to be produced in those regions.

Tracing the expression of the protein through development, Kingsley and his colleagues concluded that the sequence contributes to the development of sensory whiskers found on the faces of many mammals, and prickly surface spines found on the penises of mice and many non-human primates. Previous studies show that complete inactivation of the androgen receptor gene lead to defects in whiskers and failure to form penile spines. Although humans still retain the androgen receptor gene, the loss of regulatory information for expression in whiskers and spines could help explain two human-specific anatomical traits: absence of sensory whiskers and lack of spines on human penises. Loss of penile spines is one of several traits thought to be related to evolution of pair-bonding and monogamy in the human lineage.

The second segment of regulatory DNA they tested appears, in non-humans, near a gene called GADD45g. GADD45g normally reins in cell growth. In fact, Kingsley said, "if the gene is missing entirely, unchecked cell growth can cause pituitary tumors." When they injected the sequence into mouse eggs, they found the tell-tale blue color in a key growth layer of the developing brain -- indicating that in most animals, the regulatory sequence that has disappeared in humans restricts brain growth.

The study describes some of the changes that have helped make humans human, but there are likely to be many more, Kingsley says. "By simply changing a single gene like GADD45g you're not going to be able to explain all of human brain evolution."

Still, he adds, the study shows that "it's now possible to begin identifying some of the particular molecular changes that contribute to the evolution of human traits." Human-specific traits include not only anatomical and physiological differences, but also differences in our susceptibility to many diseases, such as arthritis, cancer, malaria, HIV, Alzheimer's, and Parkinson's. "We think that the same sorts of lists and approaches will eventually help illuminate human disease susceptibilities as well," he says. "It's a great time to be studying not only where we came from, but also how our genetic history shapes many aspects of current human biology."

Scientists Discover Anti-Anxiety Circuit in Brain Region Considered the Seat of Fear

ScienceDaily (Mar. 9, 2011) — Stimulation of a distinct brain circuit that lies within a brain structure typically associated with fearfulness produces the opposite effect: Its activity, instead of triggering or increasing anxiety, counters it.

A new study supports the role of a brain region called the amygdala in processing anxiety. In this 3-D magnetic resonance imaging (MRI) rendering of a human brain, functional MRI (fMRI) activation of the amygdala is highlighted in red.

That's the finding in a paper by Stanford University School of Medicine researchers to be published online March 9 in Nature. In the study, Karl Deisseroth, MD, PhD, and his colleagues employed a mouse model to show that stimulating activity exclusively in this circuit enhances animals' willingness to take risks, while inhibiting its activity renders them more risk-averse. This discovery could lead to new treatments for anxiety disorders, said Deisseroth, an associate professor of bioengineering and of psychiatry and behavioral science.

The investigators were able to pinpoint this particular circuit only by working with a state-of-the-art technology called optogenetics, pioneered by Deisseroth at Stanford, which allows brain scientists to tease apart the complex circuits that compose the brain so these can be studied one by one.

"Anxiety is a poorly understood but common psychiatric disease," said Deisseroth, who is also a practicing psychiatrist. More than one in four people, in the course of their lives, experience bouts of anxiety symptoms sufficiently enduring and intense to be classified as a full-blown psychiatric disorder. In addition, anxiety is a significant contributing factor in other major psychiatric disorders from depression to alcohol dependence, Deisseroth said.

Most current anti-anxiety medications work by suppressing activity in the brain circuitry that generates anxiety or increases anxiety levels. Many of these drugs are not very effective, and those that are have significant side effects such as addiction or respiratory suppression, Deisseroth said. "The discovery of a novel circuit whose action is to reduce anxiety, rather than increase it, could point to an entire strategy of anti-anxiety treatment," he added.

Ironically, the anti-anxiety circuit is nestled within a brain structure, the amygdala, long known to be associated with fear. Generally, stimulating nervous activity in the amygdala is best known to heighten anxiety. So the anti-anxiety circuit probably would have been difficult if not impossible to locate had it not been for optogenetics, a new technology in which nerve cells in living animals are rendered photosensitive so that action in these cells can be turned on or off by different wavelengths of light. The technique allows researchers to selectively photosensitize particular sets of nerve cells. Moreover, by delivering pulses of light via optical fibers to specific brain areas, scientists can target not only particular nerve-cell types but also particular cell-to-cell connections or nervous pathways leading from one brain region to another. The fiber-optic hookup is both flexible and pain-free, so experimental animals' actual behavior as well as their brain activity can be monitored.

In contrast, older research approaches involve probing brain areas with electrodes to stimulate nerve cell firing. But an electrode stimulates not only all the nerve cells that happen to be in the neighborhood but even fibers that are just passing through on the way to somewhere else. Thus, any effect from stimulating the newly discovered anti-anxiety circuit would have been swamped by the anxiety-increasing effects of the dominant surrounding circuitry.

In December 2010, the journal Nature Methods bestowed its "Method of the Year" title on optogenetics.

In the new Nature study, the researchers photosensitized a set of fibers projecting from cells in one nervous "switchboard" to another one within the amygdala. By carefully positioning their light-delivery system, they were able to selectively target this projection, so that it alone was activated when light was pulsed into the mice's brains. Doing so led instantaneously to dramatic changes in the animals' behavior.

"The mice suddenly became much more comfortable in situations they would ordinarily perceive as dangerous and, therefore, be quite anxious in," said Deisseroth. For example, rodents ordinarily try to avoid wide-open spaces such as fields, because such places leave them exposed to predators. But in a standard setup simulating both open and covered areas, the mice's willingness to explore the open areas increased profoundly as soon as light was pulsed into the novel brain circuit. Pulsing that same circuit with a different, inhibitory frequency of light produced the opposite result: the mice instantly became more anxious. "They just hunkered down" in the relatively secluded areas of the test scenario, Deisseroth said.

Standard laboratory gauges of electrical activity in specific areas of the mice's amygdalas confirmed that the novel circuit's activation tracked the animals' increased risk-taking propensity.

Deisseroth said he believes his team's findings in mice will apply to humans as well. "We know that the amygdala is structured similarly in mice and humans," he said. And just over a year ago a Stanford team led by Deisseroth's associate, Amit Etkin, MD, PhD, assistant professor of psychiatry and behavioral science, used functional imaging techniques to show that human beings suffering from generalized anxiety disorder had altered connectivity in the same brain regions within the amygdala that Deisseroth's group has implicated optogenetically in mice.

The study was funded by the National Institutes of Health, the National Institute of Mental Health, the National Institute on Drug Abuse, the National Science Foundation, NARSAD, a Samsung Scholarship, and the McKnight, Woo, Snyder, and Yu foundations. Kay Tye, PhD, a postdoctoral researcher in the Deisseroth laboratory, and Rohit Prakash, Sung-Yon Kim and Lief Fenno, all graduate students in that lab, shared first authorship. Other co-authors are graduate student Logan Grosenick, undergraduate student Hosniya Zarabi, postdoctoral researcher Kimberly Thompson, PhD, and research associates Viviana Gradinaru and Charu Ramakrishnan, all of the Deisseroth lab.