Casos de dengue aumentam 857% no município do Rio

Mais da metade dos casos notificados é de pessoas com menos de 15 anos

Retorno do sorotipo 1 é visto como a principal causa do aumento dos casos de dengue

Rio de Janeiro - O município do Rio de Janeiro teve aumento de 857% nos casos de dengue neste início de ano em comparação com o ano passado. Foram mais de 5 mil casos notificados até esta semana, enquanto no mesmo período de 2010, esse número chegou a 529 pessoas.

O município segue a tendência da região metropolitana do Rio, que teve aumento de cerca de 1000% nos casos de dengue nos primeiros dois meses do ano em comparação com o mesmo período do ano passado.

O aumento expressivo dos casos da doença é atribuído à volta do sorotipo 1, que não circulava desde 1986. Ele deixou a população mais jovem suscetível à dengue. Mais da metade dos casos notificados é de pessoas com menos de 15 anos.

De acordo com coordenador de Vigilância Ambiental da Secretaria de Saúde do Rio, Marcos Ferreira, nove bairros apresentam alta taxa de incidência da doença, com mais de 300 casos por 100 mil habitantes. Essa incidência já é considerada um surto. Pedra de Guaratiba, na zona oeste do Rio, é a campeã de vítimas do Aedes aegypti, com 941,2 casos para cada 100 mil habitantes.

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"Estamos em estado de alerta na cidade toda, mas este quadro já era esperado por causa do vírus tipo 1, que voltou e deixou vulneráveis as pessoas com menos de 25 anos. A boa notícia é que taxa de letalidade da doença diminuiu, embora o ideal é que ela fosse zero", disse Ferreira.

Apesar dos altos números, apenas Bom Jesus de Itabapoana, no noroeste do estado, apresenta quadro epidêmico. Com 33.655 habitantes, foram registrados mais de 1.100 casos até o momento. O coordenador informou que o número de registros no município do Rio é de pouco mais de 80 casos por cem mil.

Ferreira acredita que a redução do número de óbitos por dengue se deve principalmente à identificação rápida dos sintomas nos serviços de saúde do município, como o Saúde da Família e os postos.

How Breast Cell Communities Organize Into Breast Tissue

ScienceDaily (Mar. 11, 2011) — In biology, the key to a healthy life is organization. Cells that properly organize themselves into communities live long and prosper, whereas disorganized cells can become cancerous. A study by researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) of the different types of cells that make up the human breast shows that not only do cells possess an innate ability to self-organize into communities, but these communities of different types of cells can also organize themselves with respect to one another to form and maintain healthy tissue.

These image show the distribution of cell lineages in human mammary epitheial cells over time in the presence of (top) an anti--E-cadherin agent and (bottom) an anti--P-cadherin agent. LEPs are stained green, and MEPs are stained red.

Understanding this ability of different types of cell communities to self-organize into tissue may help explain how the processes of stem cell differentiation and tissue architecture maintenance are coordinated. It might also lead to a better understanding of what goes wrong in cancer.

Mark LaBarge, a cell and molecular biologist in Berkeley Lab's Life Sciences Division, and Mina Bissell, a Berkeley Lab Distinguished Scientist also with the Life Sciences Division, carried out a unique study of normal human mammary epithelial cells that had been enriched into pools of the two principal lineages that make up breast tissue -- the milk-producing luminals and the myoepithelials that blanket them. In healthy breast tissue, these two lineages organize themselves into an ordered bi-layer. To observe and quantify changes in the distribution of these cell lines with respect to one another over time, LaBarge, Bissell and a team of collaborators used a unique "micropatterning" technique, in which the cells were confined to a three-dimensional cylindrical geometry.

"We demonstrated that while bi-layered organization in mammary epithelium is driven mainly by the lineage-specific differential expression of the E-cadherin adhesion protein, the expression of the P-cadherin adhesion protein makes additional contributions that are specific to the organization of the myoepithelial layer," LaBarge says. "Disruption of these adherens junction proteins or the actomyosin network that supports them either prevented the formation of the bi-layer, or caused a loss of pre-formed bi-layers. This is the first reported evidence that the two principle lineages of adult human mammary gland possess intrinsic and reversible characteristics that guide their organization into a bi-layer."

Throughout a person's life, the various tissues in his or her body will be replenished and repaired by drawing upon a reservoir of adult stem cells. As new cells replace old ones or are used to construct new tissue, the architecture of that specific tissue must be maintained. Otherwise, cancer or other diseases can arise. This process requires that lineage-specific progenitor cells or their differentiated progeny be able to reach their ultimate destination within the tissue. This task is particularly daunting for breast cell lineages because the mammary gland undergoes cyclical changes in its architectural structure, showing as much as a 10-fold expansion in preparation for lactation followed by return to normal size. During these cycles, the precise bi-layered branching organization throughout the gland, in which a layer of secretory luminal epithelial cells (LEPs) is surrounded by a layer of contractile myoepithelial cells (MEPs), must be maintained.

"We hypothesized that mammary epithelial cells possess lineage-specific intrinsic abilities to self-organize into domains of lineage specificity, which would help explain how, for instance, the mammary stem cell-enriched zone in the ducts is maintained separately from the rank-and-file LEPs and MEPs, and how LEPs and MEPs form and maintain bi-layers," LaBarge says. "The phenomenon of self-organization has not been well studied in humans, perhaps because of the challenges of working with primary materials and a paucity of tractable culture systems for maintaining cell types from normal adult tissues."

Initially, LaBarge, Bissell and their collaborators used a classical self-organization assay, in which heterogeneous aggregates of dissociated cells from embryonic tissues were cultured on non-adherent agarose-coated surfaces, to observe organization amongst cells divided into low and high cadherin expression groups. While somewhat effective, there was a "tremendous variation" in the size and shape of the aggregations of cells that, among other factors, made watching the same cells over time "out of the question," according to LaBarge. To meet this challenge, he and his colleagues engineered a microwell culture platform that could confine mixtures of human mammary epithelial cells to a 3D cylindrical geometry.

"Suddenly, we could work with small numbers of rare cells and we could watch them in action over time and perturb the system in meaningful ways," LaBarge says, "which could all be quantified and displayed in an unbiased manner."

In addition to the micropatterned assays, LaBarge and Bissell also made use of a cell culture system invented by Martha Stampfer and Jim Garbe, both with Berkeley Lab's Life Sciences Division. This unique cell culture system made it possible for LaBarge and Bissell to carry out their study using normal human adult epithelia.

"Without the Stampfer and Garbe system, our experiments would likely have been one-offs that were subject to the genetic makeup of the host," LaBarge says. "Instead, we were able to perform the experiments many times on the same lot of isogenic LEPs and MEPs to arrive at statistically significant conclusions."

LaBarge says the discovery of the important roles played by E-cadherin and P-cadherin proteins in the organization of human LEPs and MEPs into a bi-layer was a major surprise.

"For the formation of the breast tissue bi-layer, the LEP and MEP progenitor cells need a way to get instructions, or else the differentiated LEP and MEP cells need to find their correct home," he says. "Modulation of LEP and MEP activity seems to get the cells to where they ultimately need to be, but, as other studies have suggested, there is clearly much more to maintaining a breast tissue bi-layer than just adherens like LEP and MEP."

LaBarge and Bissell reported these findings in a paper published in the Proceedings of the National Academy of Science.

This research was supported in part by a grant from the National Cancer Institute, and by Berkeley Lab's Laboratory Directed Research and Development (LDRD) funding program.

New View of Human Nerve Cells Opens Door to Potential Drug Targets

ScienceDaily (Mar. 11, 2011) — Scientists at The Scripps Research Institute and University of Pennsylvania have found a way to uncover potential drug targets that have so far remained hidden from researchers' view.

By applying the new method to a type of nerve cell critical to regulating body temperature, the authors found more than 400 "receptors" (structures that bind other molecules, triggering some effect on the cell) responding to neurotransmitters, hormones, and other chemical signals. This represents 20 to 30 times more receptors than previous studies had identified.

The technique, described in detail in a review article in the March 11, 2011 issue of the journal Pharmacology and Therapeutics, may be applied to finding "hidden" receptors in other types of nerve cells, expanding the repertoire of potential drug targets for diseases ranging from schizophrenia to Parkinson's disease.

"This technique will enable people to uncover many more drug targets," said Tamas Bartfai, chair of the Department of Molecular and Integrative Neuroscience at Scripps Research. "That may be a game changer for some diseases."

Uncovering Rare Receptors

Receptors found on cells are among the most important targets for the development of drugs because of the key roles they play in the communication circuits regulating various body functions. So far scientists have identified only a few of the receptors present on different types of nerve cells.

Bartfai's group has long been interested in a class of nerve cells in the brain called "warm sensitive neurons." These cells sense and respond to changes in body temperature, acting like a thermometer inside the brain. As body temperature increases, warm sensitive neurons become more active, telling the body to bring its temperature down. Without this regulation, body temperature could reach dangerous levels, even leading to death.

In the past 60 years, scientists had identified about a dozen receptors on warm sensitive neurons that regulate these nerve cells' activity. But Bartfai wanted to find additional receptors to better understand how the cells function.

To do so, he turned to long-time collaborator University of Pennsylvania Professor James Eberwine. Eberwine had pioneered a number of techniques to identify genes active in individual cells.

Sequencing Single Neurons

Bartfai and Eberwine took a unique approach to indentifying gene activity.

Scientists know a gene is "on" in a cell if its messenger RNA (which carries information from genes to sites of protein synthesis) is present. To study gene activity in warm sensitive cells, Eberwine and Bartfai isolated single cells and extracted their RNA. They then made cDNA copies of the messenger RNAs and determined the sequence of the nucleotide bases (adenine, guanine, cytosine, and thymine) in each cDNA molecule.

By matching the DNA sequences obtained to published sequences, the scientists were able to identify the corresponding genes, and thus which genes are turned "on" in the nerve cells.

The technique differs from commonly used methods for studying gene activity. Typically researchers "pool" neurons of one type and examine them as a group, rather than studying single cells. In addition, current techniques generally rely on searching for active genes using microarrays -- a technique that relies on the preferential binding of sequences in the messenger RNAs /cDNAs to matching DNA sequences "spotted" on the microarray. However, these methods only detect RNAs for which "probes are present on the microarray," in other words, those that are expected. Also, because of the lower sensitivity of this technique than sequencing, only the cDNAs cells produce in relatively large amounts are detected.

"Using single cells, rather than pooling, and sequencing, rather than microarrays, uncovers many more receptors active in neurons," says Bartfai. "With other methods you miss receptors present in only a few copies. But that does not mean that they are not important."

Revealing Neurons' Complexity

Using their new method Bartfai and Eberwine identified more than 400 receptors active in warm sensitive neurons. About one-third of the receptors are so-called "orphan" receptors, meaning the chemicals they bind to are unknown. The rest were receptors whose ligands (substances they bind to) are known -- among them, the authors found a few surprises.

For example, Bartfai and Eberwine discovered that the receptor responsible for binding insulin is active on warm sensitive neurons -- something no one had previously suspected.

The insulin receptor is known to be involved in regulating a person's metabolism. Follow-up studies by Bartfai's group have now shown that insulin binds to receptors on warm sensitive neurons to decrease their activity, causing an increase in body temperature, or hyperthermia. Thus, insulin is a key regulator for both body metabolism and temperature.

"This study highlights the complexity of these cells by showing us the large number of different RNAs that are present," said Eberwine.

Game-Changing Research

In addition to providing important insights into the complexity of nerve cells, the study has implications for identifying potential drug targets for diseases that currently have few or no treatments.

"We would like to repeat similar studies for key neurons involved in Parkinson's disease and schizophrenia," explained Bartfai. "If we again discover 400 receptors, we could then ask which ones are reasonably selectively expressed in these neurons." Any receptor active primarily in one class of neurons involved in a particular disease process represents a possible target for developing drugs to affect the course of that disease.

Research for the study was supported by the Harold L. Dorris Neurological Research Institute and the Skaggs Institute of Chemical Biology at Scripps Research, the National Institutes of Health, National Alliance for Research on Schizophrenia and Depression, and The Commonwealth of Pennsylvania.