Sobreviventes da gripe H1N1 têm a chave para nova vacina

As pessoas que se recuperaram da gripe H1N1, a pandemia de 2009 que ficou conhecida como "gripe suína", desenvolveram anticorpos incomuns que as protegem contra diferentes cepas de gripe, informaram cientistas nesta segunda-feira.

Os especialistas se surpreenderam ao descobrir que a imunidade dos pacientes a novas gripes poderia impulsionar as pesquisas sobre uma vacina universal contra uma série de cepas que existiram por décadas, destacou o estudo publicado no "Journal of Experimental Medicine".

Cientistas dos Estados Unidos examinaram nove pacientes que adoeceram no ano passado e descobriram neles anticorpos que, testados em ratos, os protegeram contra uma dose letal de pelo menos outras três cepas de gripe, inclusive a aviária.

"O resultado é algo assim como o Santo Graal para a pesquisa com vacinas contra a gripe", disse o autor do estudo, Patrick Wilson, professor assistente de medicina da Universidade de Chicago.

"Demonstra como fazer uma única vacina que potencialmente poderia imunizar contra todas as influenzas", disse.

Alguns pacientes --a maioria com idade entre 20 e 30 anos-- tinham uma forma leve de gripe, que foi curada em alguns dias; outros tiveram uma forma mais severa, que exigiu hospitalização durante até dois meses.

Em amostras de sangue tiradas dez dias depois de os pacientes apresentarem os sintomas, os cientistas descobriram e isolaram os anticorpos produzidos contra o vírus.

"Cinco anticorpos isolados pela equipe atacaram todas as cepas sazonais da gripe H1N1 da última década, a devastadora 'gripe espanhola' de 1918 e também a patogênica gripe aviária H5N1", destacou o estudo.

O vírus H1N1 infectou 60 milhões de pessoas. Detectada pela primeira vez em 2009, no México, esta forma da doença foi particularmente perigosa para crianças e mulheres grávidas, diferentemente de outras cepas que tendem a ser mais letais entre os idosos.

Antidepressivo pode ajudar a recuperar vítimas de derrame

Receitar o antidepressivo Prozac para pessoas que acabaram de ter um AVC (acidente vascular cerebral) pode ajudá-las a recuperar o controle sobre seus movimentos, disseram cientistas nesta segunda-feira.

No estudo sobre o efeito deste tipo de antidepressivo na recuperação de AVC, investigadores franceses descobriram que pacientes com derrame que tomaram Prozac melhoraram sua pontuação em testes de habilidades motoras em relação àqueles que receberam um placebo.

Peritos que comentaram os resultados disseram que o Prozac tinha "um potencial enorme para mudar a prática clínica".

O AVC é a principal causa de incapacidade em adultos e a terceira maior causa de morte no mundo desenvolvido.

O custo de cuidar das vítimas, que muitas vezes têm dificuldades motoras como fraqueza ou paralisia em um lado do corpo, pode ser um fardo para o sistema de saúde.

Alguns pequenos estudos anteriores já haviam sugerido que receitar drogas como o Prozac, que pertence a uma classe de medicamentos conhecidos como inibidores seletivos de recaptação de serotonina (SSRIs), poderia melhorar a recuperação de habilidades motoras após o acidente vascular cerebral.

Hemiplegia --paralisia de um lado do corpo-- e hemiparesia --fraqueza em um lado do corpo-- são as deficiências mais comuns do AVC e os cientistas acreditam que os SSRIs podem ajudar a melhorar a circulação, aumentando o nível de serotonina do cérebro no sistema nervoso central.

"O efeito positivo da droga sobre a função motora sugere que a ação neuronal de SSRIs fornece um novo caminho que deve ser aprofundado", disse François Chollet do Hospital Universitário de Toulouse, que conduziu a investigação.

No estudo, realizado entre março de 2005 e junho de 2009 e publicado na revista "Lancet Neurology" nesta segunda, 118 pacientes franceses receberam Prozac ou um placebo durante três meses, entre cinco e dez dias após ter sofrido um derrame.

Todos os pacientes também fizeram fisioterapia e tiveram suas habilidades motoras testadas no início do experimento e depois de 90 dias.

Foram registradas melhorias significativamente maiores na função motora dos pacientes que tomaram Prozac, onde a pontuação média nos testes aumentou 34 pontos. No grupo do placebo, o aumento médio foi de 24,3 pontos.

Antibiotic Resistance Is Not Just Genetic

ScienceDaily (Jan. 10, 2011) — Genetic resistance to antibiotics is not the only trick bacteria use to resist eradication- they also have a second defence strategy known as persistence that can kick in.

Wild-type Pseudomonas aeruginosa bacterium.

Researchers reporting in the Journal of Medical Microbiology have now demonstrated for the first time that interplay occurs between the two mechanisms to aid bacterial survival. The findings could lead to novel, effective approaches to treat multi-drug resistant (MDR) infections.

'Persister' bacterial cells are temporarily hyper-resistant to all antibiotics at once. They are able to survive (normally) lethal levels of antibiotics without being genetically resistant to the drug. These cells are a significant cause of treatment failure yet the mechanism behind the persistence phenomenon is still unclear.

Scientists from Centre of Microbial and Plant Genetics, at the Katholieke Universiteit Leuven, Belgium found that the number of persister cells isolated from Pseudomonas aeruginosainfections decreases when the bacterial population shows genetic resistance to the antibiotic fosfomycin.

P. aeruginosa is an opportunistic human pathogen and a significant cause of hospital-acquired infections. It can cause fatal infections in people suffering from cystic fibrosis. The bacterium is notorious for its ability to develop resistance against commonly-used antibiotics and treatment failure is common.

Professor Jan Michiels who led the study explained that persister cells are a major contributor to treatment failure. "Persister cells are produced in low numbers, but nevertheless make it almost impossible to completely remove the bug from the patient. As a result, eradication of infections through antibiotic treatment usually takes a long time," he said. "Our work shows that antibiotic treatment may also influence the number of persisters formed."

Co-administration therapies are being developed to treat MDR infections, in which drugs targeting non-essential cellular functions are combined with antibiotics. Professor Michiels explained that targeting persistence is an attractive option. "Ideally both susceptible and persistent cells would be targeted in a single therapy, but firstly we need to understand more about the interplay between genetic resistance and persistence to avoid stimulating one or the other. Unravelling the mechanism behind bacterial persistence is really important to enable us to optimise treatments of chronic bacterial infections."

Induced Pluripotent Stem Cells from Fetal Skin Cells and Embryonic Stem Cells Display Comparable Potential for Derivation of Hepatocytes

ScienceDaily (Jan. 10, 2011) — Numerous patients suffering from chronic liver diseases are currently receiving inadequate treatment due to the lack of organs donated for transplantation. However, hepatocytes derived from induced pluripotent stem cells (iPSCs) could offer an alternative for the future. Scientists from the Max Planck Institute for Molecular Genetics in Berlin compared hepatocytes from embryonic stem cells with hepatocytes from iPS cells and found that their gene expression is very similar.

Real hepatocytes, so-called primary hepatocytes (A), hepatocyte-like cells from embryonic stem cells (B) and induced pluripotent stem cells from foetal skin cells (C). Gene expression of induced pluripotent stem cells (iPSCs), human embryonic stem cells (hESCs), hepatocytes derived from them (Hep-iPSCs, Hep-hESCs) and foetal hepatocytes. Although the hepatocyte-like cells from embryonic stem cells and induced pluripotent stem cells differ from primary hepatocytes, they still share ca. 53 per cent of gene expression with these cells. (Credit: Max Planck Institute for Molecular Genetics)

Nevertheless, in comparison to "real" hepatocytes, just under half of the genes exhibited a different gene expression. Therefore, the gene expression of hepatocytes derived from iPS cells still requires adaptation before the cells could be used in the treatment of liver diseases.

The research is published in Stem Cells and Development (Dec. 20, 2010).

Induced pluripotent stem cells can be derived from different cell types and have the same genetic background as their progenitors. Hepatocytes derived from iPSCs therefore constitute an ideal point of departure for future regenerative therapy, as immune rejection between donor and host cells can be avoided.

In their study, the Max Planck scientists compared hepatocyte-like cells derived from iPS cells and embryonic stem cells with "real" hepatocytes in early and later stages of development. Justyna Jozefczuk from the Max Planck Institute for Molecular Genetics explains: "It is the only way to determine actual differences between the cell types, and any flaws still present in the 'synthetic' hepatocytes." The scientists were able to show that the gene expression of hepatocytes based on embryonic stem cells and iPSCs is about 80 per cent similar. However, compared to isolated cells from the foetal human liver, the gene expression match is only 53 per cent.

Hepatocyte-like cells from iPSCs and embryonic stem cells activate many of the typical liver proteins, e.g., albumin, alpha-fetoprotein and cytokeratin 18. Moreover, the "synthetic" hepatocytes can store glycogen and produce urea, just like the "real" hepatocytes. In addition, they are able to absorb and break down foreign molecules. In contrast, the genes around the enzyme group cytochrome P450 in the iPSCs and in real hepatocytes display different expression levels. These enzymes metabolise, among other things, drugs and foreign substances.

"This knowledge not only helps us better understand the causes of liver diseases; it also allows us to develop more efficient, patient-specific drugs," says James Adjaye from the Max Planck Institute for Molecular Genetics.

Cancer in a Single Catastrophe: Chromosome Crisis Common in Cancer Causation

ScienceDaily (Jan. 10, 2011) — Remarkable new research overthrows the conventional view that cancer always develops in a steady, stepwise progression. It shows that in some cancers, the genome can be shattered into hundreds of fragments in a single cellular catastrophe, wreaking mutation on a massive scale.

Evidence of chromothripsis in small cell lung cancer. (Credit: Stephens PJ et al. (2011) Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell)

The scars of this chromosomal crisis are seen in cases from across all the common cancer types, accounting for at least one in forty of all cancers. The phenomenon is particularly common in bone cancers, where the distinctively ravaged genome is seen in up to one in four cases.

The team looked at structural changes in the genomes of cancer samples using advanced DNA sequencing technologies. In some cases, they found dramatic structural changes affecting highly localised regions of one or a handful of chromosomes that could not be explained using standard models of DNA damage.

"The results astounded us," says Dr Peter Campbell, from the Cancer Genome Project at the Wellcome Trust Sanger Institute and senior author on the paper. "It seems that in a single cell in a single event, one or more chromosomes basically explode -- literally into hundreds of fragments.

"In some instances -- the cancer cases -- our DNA repair machinery tries to stick the chromosomes back together but gets it disastrously wrong. Out of the hundreds of mutations that result, several promote the development of cancer."

Cancer is typically viewed as a gradual evolution, taking years to accumulate the multiple mutations required to drive the cancer's aggressive growth. Many cancers go through phases of abnormal tissue growth before eventually developing into malignant tumours.

The new results add an important new insight, a new process that must be included in our consideration of cancer genome biology. In some cancers, a chromosomal crisis can generate multiple cancer-causing mutations in a single event.

"We suspect catastrophes such as this might happen occasionally in the cells of our body," says Dr Andy Futreal, Head of Cancer Genetics and Genomics at the Wellcome Trust Sanger Institute and an author on the paper. "The cells have to make a decision -- to repair or to give up the ghost.

"Most often, the cell gives up, but sometimes the repair machinery sticks bits of genome back together as best it can. This produces a fractured genome riddled with mutations which may well have taken a considerable leap along the road to cancer."

The new genome explosions caused 239 rearrangements on a single chromosome in one case of colorectal cancer.

The damage was particularly common in bone cancers, where it affected five of twenty samples. In one of these samples the team found three cancer genes that they believe were mutated in a single event: all three are genes that normally suppress cancer development and when deleted or mutated can lead to increased cancer development.

"The evidence suggests that a single cellular crisis shatters a chromosome or chromosomes," says Professor Mike Stratton, Director of the Wellcome Trust Sanger Institute and an author on the paper, "and that the DNA repair machinery pastes them back together in a highly erroneous order.

"It is remarkable that, not only can a cell survive this crisis, it can emerge with a genomic landscape that confers a selective advantage on the clone, promoting evolution towards cancer."

The team propose two possible causes of the damage they see. First, they suggest it might occur during cell division, when chromosomes are packed into a condensed form. Ionizing radiation can cause breaks like those seen. The second proposition is that attrition of telomeres -- the specialized genome sequences at the tips of chromosomes -- causes genome instability at cell division.

This work was supported by the Wellcome Trust and the Chordoma Foundation.

Extracting Cellular 'Engines' May Aid in Understanding Mitochondrial Diseases

ScienceDaily (Jan. 10, 2011) — Medical researchers who crave a means of exploring the genetic culprits behind a host of neuromuscular disorders may have just had their wish granted by a team working at the National Institute of Standards and Technology (NIST), where scientists have performed surgery on single cells to extract and examine their mitochondria.

Extracting mitochondria from a human cell is a tricky process. NIST researchers recently developed techniques that can surgically remove these tiny cellular engines, potentially enabling new ways to explore the link between mitochondrial DNA and a host of diseases. (Credit: NIST)

The scientists reached into these cells and extracted their "engines" -- the mitochondria that are in large part responsible for our metabolism. Many human cells contain hundreds of mitochondria, which were thought to be free-swimming organisms millions of years ago and which still possess their own DNA. Mutations in this mitochondrial DNA (mtDNA) are directly related to a large class of mitochondrial-based diseases, which have a range of symptoms that include early onset blindness, seizures, hearing loss, dementia, etc. In the general population, one out of every 200 people possesses a mtDNA mutation that may develop into a mitochondrial disease.

Investigating more deeply has been problematic, though, because the way mitochondria mix and spread their DNA within and among cells is poorly understood. "The trouble is that it's very difficult to extract single mitochondria from an individual cell," says NIST physicist Joseph Reiner. "For years, the best technique has been to break open a group of cells and collect the mitochondria from all of them in a kind of soup. As you might guess, it's hard to determine which mitochondria came from what cells -- yet that's what we need to know."

The research team, which also includes scientists from Gettysburg College, has potentially solved this problem by realizing that several devices and techniques can be used together to extract a single mitochondrion from a cell that possesses a genetic mutation. They employed a method previously used to extract single chromosomes from isolated rice cells where a laser pulse makes an incision in a cell's outer membrane. Another laser is used as a "tweezer" to isolate a mitochondrion, which then can be extracted by a tiny pipette whose tip is less than a micrometer wide.

This approach allowed the team to place a single mitochondrion into a small test tube, where they could explore the mitochondrion's genetic makeup by conventional means. The team found the mutation present throughout the entire cell was also found within individual mitochondria, a find suggesting that broad genetic research on mitochondrial disease may be possible at last.

"Getting an object as tiny as this from tweezer to test tube is not easy," says Koren Deckman, a biochemist from Gettysburg College. "But by building on more than a decade of work that has gone on at NIST and elsewhere, we now have a way to see the mitochondria we extract all the way through the transfer process, meaning we can be sure the sample came from a very specific cell. This could give medical scientists the inroad they need for understanding these diseases."