Mosquito da dengue infectado vive menos

Efeitos no mosquito

O que a dengue causa ao ser humano já é bem conhecido.

Mas o que a infecção pelo vírus da dengue causa ao próprio mosquito Aedes aegypti?

Este foi o tema da pesquisa realizada por Ricardo Lourenço e seus colegas do Instituto Oswaldo Cruz (IOC/Fiocruz).

Os resultados mostraram que as fêmeas infectadas viveram em média 15 dias a menos do que as não infectadas e apresentaram uma queda no número de ovos colocados a partir da terceira postura.

Esforço de defesa

Segundo Ricardo Lourenço, a redução do tempo de vida médio do A. aegyptiinfectado pode estar ligada ao esforço que o mosquito precisa fazer para se defender do vírus em seu organismo.

O estudo optou por observar fêmeas do A. aegypti porque apenas elas se alimentam de sangue, atuando portanto na transmissão da dengue.

"A hipótese para explicar esta observação é a de que o gasto desprendido pelo mosquito para se defender do vírus em seu corpo comprometa sua produção de ovos e outros aspectos de sua biologia e comportamento", complementa.

Alimentação do mosquito

A investigação reforça uma abordagem recente dos estudos na área, que passa a considerar os efeitos acarretados pelo vírus no organismo do A. aegypti e sua interferência no ciclo de transmissão.

Há cerca de 10 anos, os pesquisadores achavam que o vírus não alterava a vida do mosquito. Mas essa crença vem sendo alterada com base em estudos de "longo prazo": "Em nosso estudo, conseguimos observar os mosquitos ao longo de várias semanas. Com isso, vimos que a infecção no mosquito pode interferir na sua vida e, por conseguinte, no ciclo de transmissão da dengue", diz o especialista.

O próximo passo da pesquisa é a investigação do efeito da infecção pelo vírus sobre os hábitos alimentares do vetor. "Queremos saber se a infecção causa alguma alteração relacionada à picada do mosquito", finaliza o pesquisador.

Ingrediente do vinho interrompe crescimento de células do câncer de mama

Amigo do peito

Uma nova pesquisa revelou que o resveratrol, considerado o ingrediente saudável do vinho tinto, bloqueia o crescimento de células do câncer de mama.

Segundo cientistas da Universidade da Calábria (Itália), o resveratrol bloqueia os efeitos do hormônio estrogênio, reduzindo os receptores específicos das células do câncer de mama.

Apesar dos seguidos estudos que concluem pelos benefícios do composto presente no vinho tinto e nos sucos de uvas escuras, esta é a primeira vez que se demonstra sua ação especificamente contra o câncer de mama.

Resveratrol

"O resveratrol é uma ferramenta farmacológica que pode ser usada quando o câncer de mama se torna resistente à terapia hormonal," afirma o Dr. Sebastiano Andò, membro da equipe.

Ele e seus colegas usaram linhagens de células do câncer de mama, que expressavam o receptor do estrogênio, para testar os efeitos do resveratrol.

Os pesquisadores trataram um grupo de células com o composto e compararam seu crescimento com as células não-tratadas.

O estudo mostrou uma redução no crescimento das células tratadas com resveratrol, e nenhuma modificação, isto é, crescimento normal, nas células não-tratadas.

Produtos naturais

Experimentos adicionais revelaram que o efeito deu-se devido a uma drástica redução nos níveis dos receptores de estrogênio das células, o que foi causado pelo resveratrol.

"Estas descobertas são entusiasmantes, mas de jeito nenhum significam que as pessoas devem sair e começar a beber vinho tinto ou suplementos como tratamento para o câncer de mama," alerta o pesquisador.

"O que estas descobertas significam é que os cientistas ainda não terminaram o trabalho de destilar os segredos da boa saúde que estão escondidos em produtos naturais, como o vinho tinto," concluiu Andò.

Exame PSA faz mais mal do que bem, dizem especialistas

Sem benefícios

Os médicos devem parar de pedir exames preventivos para câncer de próstata porque eles fazem mais mal do que bem.

Este conselho contundente vem agora, mais de uma década depois da introdução do exame PSA, o antígeno prostático específico.

"O rastreamento para câncer de próstata com base no PSA não tem benefício líquido," concluiu a Força-Tarefa de Serviços Preventivos, dos Estados Unidos, que avalia serviços médicos de triagem.

Disfunção erétil

Os perigos das campanhas preventivas com base no PSA incluem uma alta taxa de falsos positivos, efeitos psicológicos negativos e complicações associadas com biópsias e tratamentos, diz a força-tarefa.

Entre 1986 e 2005, 1 milhão de homens nos EUA passaram por cirurgia e radioterapia para câncer de próstata após um teste de PSA.

Mas os especialistas não encontraram nenhuma evidência de que estes tratamentos tenham impedido mais mortes do que o padrão "observar e esperar", quando a saúde do paciente é monitorada com cuidado até que sinais mais consistentes da doença indiquem a necessidade real do tratamento.

No entanto, entre 200 e 300 homens em cada mil tratados - entre 20 e 30% - desenvolveram incontinência ou disfunção erétil, o que é visto pelos especialistas como um efeito colateral desses tratamentos cuja necessidade não se comprovou.

Contrários e a favor

"É encorajador ver um debate verdadeiro sobre o impacto dos exames de PSA nos resultados para o paciente", comentou John Semmes, da Eastern Virginia Medical School.

"Eu penso que a decisão é prematura porque há mais dados sendo produzidos que podem indicar se a triagem é benéfica ou não," ponderou Freddie Hamdy, da Universidade de Oxford, que está fazendo a mesma avaliação no Reino Unido.

Por outro lado, médicos europeus descartaram os exames de câncer de próstata como rotina no início do ano passado.

William Catalona, diretor do programa clínico de câncer de próstata da Universidade Northwestern, em Chicago, concorda:

"O PSA é o melhor teste de triagem que temos para o câncer de próstata, e até que haja um substituto, seria inconcebível parar de fazê-lo," diz ele.

Na verdade, já existe um novo exame, chamado A+PSA, aguardando aprovação pelas autoridades de saúde:

• Novo exame da próstata é mais preciso do que PSA

Good Housekeeping Maintains a Healthy Liver

ScienceDaily (Oct. 17, 2011) — Differences in the levels of two key metabolic enzymes may explain why some people are more susceptible to liver damage, according to a study in the October 17 issue of theJournal of Cell Biology.

A new study in the Journal of Cell Biology suggests that differential expression of GAPDH and NDPK, two key metabolic enzymes, may explain why some people are more susceptible to liver damage.Compared to control cells (left), liver cells lacking GAPDH (right) show increased levels of reactive oxygen species (green) after treatment with the liver-damaging drug DDC.

Some forms of liver disease, particularly steatohepatitis, are marked by the formation of misfolded protein aggregates called Mallory-Denk bodies (MDBs). Not all patients display these aggregates, however, and some research suggests that MDBs are more common in patients of Hispanic origin. Different strains of mice also show different susceptibilities to MDB formation when their livers are damaged by the drug DDC, which induces oxidative stress. A team led by researchers from the University of Michigan analyzed the proteomes of livers from two different mouse strains to investigate the cause of their different sensitivities to DDC.

Many metabolic and oxidative stress-related enzymes were expressed at differing levels in the livers of C57BL (MDB-susceptible) and C3H (MDB-resistant) mice, resulting in higher levels of reactive oxygen species in C57BL liver cells after DDC treatment. Prominent among these enzymes were two general "housekeeping" proteins: the metabolic enzyme GAPDH and the energy-generating protein NDPK, both of which showed reduced expression in C57BL livers and were decreased further by DDC treatment.

Depleting GAPDH or NDPK by RNAi elevated reactive oxygen species levels similarly to DDC treatment, whereas overexpressing GAPDH prevented DDC from inducing reactive oxygen species production in C57BL liver cells. The authors think that low GAPDH and NDPK expression causes C57BL livers to be metabolically and oxidatively stressed even under normal conditions and therefore more sensitive to additional stresses like DDC treatment. The researchers also found that GAPDH is localized in protein aggregates in cirrhotic patient livers, suggesting that similar mechanisms may contribute to liver disease severity in humans.

Skin's Immune Peacekeepers Discovered

ScienceDaily (Oct. 17, 2011) — There are more bacteria living on our skin and in our gut than cells in our body. We need them. But until now no one knew how the immune system could tell that these bacteria are harmless. Centenary Institute researchers in Sydney have discovered a set of peacekeepers -- immune cells in the outer layers of our skin that stop us from attacking friendly bacteria.

Image of langerhans cells in skin (from a genetically engineered mouse where LCs express yellow fluorescent protein).

The work will open the way to new therapeutic options for immune-mediated diseases such as inflammatory bowel disease, of which Australia has some of the world's highest rates.

In a paper published October 17 in the Proceedings of the National Academy of Sciences (PNAS), Professor Barbara Fazekas de St Groth and her team have shown that the immune cells in the outer layer of the skin constantly act as peacekeepers to stop the immune system from reacting the way it normally would. Known as Langerhans cells, they resisted every attempt by the researchers to get them to generate an immune response.

The researchers worked with a group of mice in which only the Langerhans cells could stimulate the immune system. They then activated the Langerhans cells and measured the response.

"No matter what we threw at them to get them to activate a long-term immune response, the Langerhans cells always induced immune tolerance," Prof Fazekas says.

This result seems to go against the prevailing wisdom in immunology about the workings of dendritic cells, the class of immune cell to which Langerhans cells belong.

Dendritic cells engulf bacteria, viruses or other invaders and put a marker from that invader, known as an antigen, on a protein that can bind to other immune cells.

The antigen reprograms passing T cells, the workhorses of the immune system, which then set off a cascade of responses that eventually lead to the destruction of anything displaying that antigen.

However, the Centenary team (which is affiliated with the University of Sydney and RPA Hospital) found Langerhans cells are very different from other dendritic cells: after turning on the helper T cells, they tell them to self-destruct instead.

"This is the opposite of what you'd usually expect. In previous studies of immune cells, if there was a flurry of activity, we assumed it was the start of a long-term immune response," Prof Fazekas says.

However, the immune system is a layered defence¬ -- the next layer of skin has different kinds of dendritic cells, which program on-going responses against bacteria. So if bacteria penetrate deep enough to meet these cells, the immune response will kill them.

In inflammatory bowel disease, which afflicts thousands of Australians, the immune system is activated against the gut bacteria, which are usually left alone.

This discovery opens up possible ways to figure out why this disorder occurs and to find treatments to a range of diseases of the immune system.

"There is so much we don't know about the immune system, but sometimes just mimicking what the system does, like we do with vaccines, can work very well" Prof Fazekas says,

"If we do manage to mimic what Langerhans cells do, then we could develop treatments that would precisely tolerise against specific antigens -- just like the immune system of the skin does now."

Centenary Institute executive director Professor Mathew Vadas says this latest paper comes just weeks after Centenary researcher Patrick Bertolino made the front cover of PNAS for his paper on immune response in the liver.

"The Centenary Institute is interested in understanding how the immune system works -- these discoveries and others already in the pipeline here are a major step forward towards that goal," Prof Vadas says.

Inhibiting Allergic Reactions Without Side Effects

ScienceDaily (Oct. 17, 2011) — Researchers from the University of Notre Dame have announced a breakthrough approach to allergy treatment that inhibits food allergies, drug allergies, and asthmatic reactions without suppressing a sufferer's entire immunological system.

Backbone alignment of IgG, IgE, and IgM antibody crystal structure, including residues of the conserved nucleotide binding pocket.

The therapy centers on a special molecule the researchers designed, a heterobivalent ligand (HBL), which when introduced into a person's bloodstream can, in essence, out-compete allergens like egg or peanut proteins in their race to attach to mast cells, a type of white blood cell that is the source of type-I hypersensitivity (that is, allergy).

"Unlike most current treatments, this approach prevents allergic reactions from occurring in the first place" says Basar Bilgicer, assistant professor of Chemical and Biomolecular Engineering and Chemistry and Biochemistry and principal investigator in Notre Dame's Advanced Diagnostics & Therapeutics initiative.

Michael Handlogten, lead scientist on the paper and a graduate student in Dr. Bilgicer's group, explained that among the various chemical functionalities he analyzed to be used as the scaffold HBL synthesis, ethylene glycol, an FDA-approved molecule, proved to be the most promising.

Mast cells are part the human body's defense against parasites (such as tapeworms), and when working normally they are attracted to, attach to, and annihilate these pathogens. But type-I hypersensitivity occurs when the cells react to non-threatening substances. More common allergies are due to ambient stimulants, and an allergic response may range from a mild itch to life-threatening anaphylactic shock.

Tanyel Kiziltepe, a research professor in Advanced Diagnostics & Therapeutics, adds that "anaphylaxis can be caused by certain food allergens, insect stings, antibiotics, and some medicines, and we believe HBL has a very high potential to be developed as a preventative medication."

While many medicines treat allergies by weakening a person's entire immune system, this approach only disrupts the process whereby white blood cells bond with allergens in the first place.

"It also does not leave patients open to an increased risk for infections or the development of cancers," explains Bilgicer. "HBLs may be most useful in situations where it's not possible to speak to or gauge someone's sensitivity."

"For example, in an emergency, on a battlefield, or in a remote location, doctors may not be able to ask a patient about an allergy before administering penicillin. An engineered HBL could be given along with the medicine and perhaps prevent a deadly reaction from occurring."

In a normal allergic reaction, allergens bind to a white blood cell, or "mast" cell, and cause the release of inflammatory molecules. Researchers at Notre Dame have shown how non-allergenic molecules, known as heterobivalent ligands, can be designed to attach to mast cells first, preventing the allergic reaction in the first place.

Precise Gene Therapy Without a Needle

ScienceDaily (Oct. 17, 2011) — For the first time, researchers have found a way to inject a precise dose of a gene therapy agent directly into a single living cell without a needle.

Researchers at Ohio State University have discovered a way to deposit gene therapy agents in living cells without the use of a needle. Images courtesy of Ohio State University. Above, two tiny reservoirs (measured in micrometers, or millionths of a meter) are connected by a nanometer- (billionth of a meter) sized channel, which is too small to be seen at this magnification.

The technique uses electricity to "shoot" bits of therapeutic biomolecules through a tiny channel and into a cell in a fraction of a second.

L. James Lee and his colleagues at Ohio State University describe the technique in the online edition of the journal Nature Nanotechnology, where they report successfully inserting specific doses of an anti-cancer gene into individual leukemia cells to kill them.

They have dubbed the method "nanochannel electroporation," or NEP.

"NEP allows us to investigate how drugs and other biomolecules affect cell biology and genetic pathways at a level not achievable by any existing techniques," said Lee, who is the Helen C. Kurtz Professor of Chemical and Biomolecular Engineering and director of the NSF Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices at Ohio State.

There have long been ways to insert random amounts of biomaterial into bulk quantities of cells for gene therapy. And fine needles can inject specific amounts of material into large cells. But most human cells are too small for even the smallest needles to be of any use.

NEP gets around the problem by suspending a cell inside an electronic device with a reservoir of therapeutic agent nearby. Electrical pulses push the agent out of the reservoir and through a nanometer- (billionth of a meter) scale channel in the device, through the cell wall, and into the cell. Researchers control the dose by adjusting the number of pulses and the width of the channel.

In Nature Nanotechnology, they explain how they constructed prototype devices using polymer stamps. They used individual strands of DNA as templates for the nanometer-sized channels.

Lee invented the technique for uncoiling strands of DNA and forming them into precise patterns so that they could work as wires in biologically based electronics and medical devices. But for this study, gold-coated DNA strands were stretched between two reservoirs and then etched away, in order to leave behind a nano-channel of precise dimensions connecting the reservoirs within the polymeric device.

Electrodes in the channels turn the device into a tiny circuit, and electrical pulses of a few hundred volts travel from the reservoir with the therapeutic agent through the nano-channel and into a second reservoir with the cell. This creates a strong electric field at the outlet of the nano-channel, which interacts with the cell's natural electric charge to force open a hole in the cell membrane -- one large enough to deliver the agent, but small enough not to kill the cell.

In tests, they were able to insert agents into cells in as little as a few milliseconds, or thousandths of a second.

First, they tagged bits of synthetic DNA with fluorescent molecules, and used NEP to insert them into human immune cells. After a single 5-millisecond pulse, they began see spots of fluorescence scattered within the cells. They tested different pulse lengths up to 60 milliseconds -- which filled the cells with fluorescence.

To test whether NEP could deliver active therapeutic agents, they inserted bits of therapeutic RNA into leukemia cells. Pulses as short as 5 milliseconds delivered enough RNA to kill some of the cells. Longer pulses -- approaching 10 milliseconds -- killed almost all of them. They also inserted some harmless RNA into other leukemia cells for comparison, and those cells lived.

At the moment, the process is best suited for laboratory research, Lee said, because it only works on one cell or several cells at a time. But he and his team are working on ways to inject many cells simultaneously. They are currently developing a mechanical cell-loading system that would inject up to 100,000 cells at once, which would potentially make clinical diagnostics and treatments possible.

"We hope that NEP could eventually become a tool for early cancer detection and treatment -- for instance, inserting precise amounts of genes or proteins into stem cells or immune cells to guide their differentiation and changes -- without the safety concerns caused by overdosing, and then placing the cells back in the body for cell-based therapy," Lee added.

He sees potential applications for diagnosing and treating leukemia, lung cancer, and other tumors. He's working with researchers at Ohio State's Comprehensive Cancer Center to explore those possibilities.

Coathors on the paper include Pouyan Boukany, Andrew Morss, Wei-ching Liao, Brian Henslee, Xulang Zhang, Bo Yu, Xinmei Wang, Yun Wu, HyunChul Jung, Lei Li, Keliang Gao, Xin Hu, Xi Zhao, O. Hemminger, Wu Lu, and Gregory P. Lafyatis, all of Ohio State.